advances in the treatment of rare...

Advances in the Treatment of Rare Diseases

Contained within these pages are the realized hopes and dreams of millions of

Americans affected by rare diseases. A Decade of Innovation doesn’t just describe a

period of stunning medical advances, it documents a brief window in time during

which people without hope learned to believe again that they might have a future.

This book tells the stories of numerous individuals and the remarkable legislation

—the Orphan Drug Act of 1983—that has given them back their lives. The National

Organization for Rare Disorders (NORD) is grateful to PhRMA for focusing this

spotlight on rare diseases. We look forward to continued partnership with all those

involved in the rapidly unfolding drama of bringing safe and effective new treat-

ments to market for the 25 million Americans with rare diseases.

Abbey S. Meyers Carolyn Asbury, PhD

President Chairman, Board of Directors

NORD NORD

Genetic Alliance applauds these advances in treating rare diseases. We are grateful

that the continuum of basic science to medical services is infused with the time,

energy, and resources of many talented individuals, particularly those who are part

of the member companies of PhRMA. Genetic Alliance members, 600 disease

advocacy organizations, representing over 1,000 diseases, look forward to the day

they too will celebrate a treatment. Meanwhile, we stand beside you in gratitude and

support your marvelous accomplishments.

Sharon F. Terry

President and CEO

Genetic Alliance

• interstitial cystitis: pentosan polysulfate sodium • neurocystericercosis and hydatid disease:

albendazole • symptomatic orthostatic hypotension: midodrine

hydrochloride

2004

2005

2003

2001

1998

1996

1995

• T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma: nelarabine

• chronic iron overload: deferasirox• advanced renal cell carcinoma: sorafenib tosylate• myelodysplastic disorder: lenalidomide• mucopolysaccharidosis VI: galsulfase• severe primary IGF-1 deficiency: mecasermin• glioblastoma: temozolomide

• secondary hyperparathyroidism: cinacalcet• malignant pleural mesothelioma: pemetrexed• acute lymphoblastic leukemia: clofarabine• pulmonary arterial hypertension: iloprost

• CD20-positive follicular non-Hodgkin’s lymphoma:tositumomab and Iodine-131 tositumomab

• Fabry disease: agalsidase beta• type 1 Gaucher disease: miglustat• acromegaly: pegvisomant

• hereditary tyrosinemia type 1: nitisinone• Cryptosporidium parvum or Giardia lamblia:

nitazoxanide• cataplexy associated with narcolepsy: sodium oxybate • pulmonary arterial hypertension: treprostinil

• chronic myeloid leukemia: imatinib mesylate• pulmonary arterial hypertension: bosentan

• acute promyelocytic leukemia: arsenic trioxide• acute myeloid leukemia: gemtuzumab

• hypoxic respiratory failure in newborns: nitric oxide • respiratory distress syndrome in premature infants:

poractant alfa • anaplastic astrocytoma: temozolomide

1999

• Crohn’s disease: infliximab • pulmonary tuberculosis: rifapentine • narcolepsy: modafinil • erythema nodosum leprosum: thalidomide • thrombocytopenia: lepirudin

• pediatric respiratory distress syndrome: calfactant • hemophilia B: recombinant human Factor IX

• amyotrophic lateral sclerosis: riluzole • primary pulmonary hypertension: epoprostenol

1997

2000

2002

RARE DISEASES

TABLE OF CONTENTS

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3

Metabolic Disorders

Fabry Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4

Gaucher Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4

Mucopolysaccharidosis VI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5

Rare Blood Pressure Disorders

Pulmonary Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6

Hypotension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7

Crohn’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Interstitial Cystitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Hyperparathyroidism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

Diseases of the Developing World

Cryptosporidiosis and Giardiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

Neurocysticercosis and Hydatid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12

Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13

Blood Disorders

Thrombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

Hemophilia B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15

Childhood Diseases

Respiratory Distress Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

Tyrosinemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

Primary IGF-1 Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17

Narcolepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18

ALS/Lou Gehrig’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18

Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20

Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

Endnotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26

In the last 10 years, biopharmaceutical companies have

made great progress in the fight against rare diseases.

Over 160 drugs were approved during the past decade

(1995–2005) to treat rare or “orphan” diseases that

affect 200,000 or fewer people in the United States.

This compares with 108 approvals in the decade before

(1984–1994) and fewer than 10 in the 1970s.1 Each of

these medicines offers hope and relief to patients with

diseases that often have no other treatment options.

According to the National Institutes of Health Office of

Rare Diseases, there are 6,000–7,000 rare diseases

affecting a total of 25 million Americans.2,3 One in every

10 Americans receives a diagnosis of a rare disease.4

This population is particularly in need of medicines

because, as the FDA estimates, 85–90 percent of rare

diseases are serious or life-threatening.5

Why has the number of orphan drugs being approved

grown so much in recent years? One factor is advances

in science; a better understanding of molecular and

genetic causes of disease has given us new tools to

explore rare diseases, which are often more complex

than more common diseases. Another factor is the huge

and growing investment in research and development

in general, as well as in orphan diseases specifically.

The Orphan Drug Act, passed in 1983, provided tax

relief and some marketing exclusivity for companies

who develop an orphan drug. This legislation is

credited with the explosion in drug approvals

for rare diseases after the Act was passed in 1983.

Today, the number of new drugs in development for

rare diseases continues to rise. This report high-

lights some of the many important drugs for rare

diseases that have been approved in the last decade.

These medicines have meant a completely differ-

ent life today for many patients with rare diseases

compared with just a few years ago. And, scientists

are working each day to make the coming decades as

bright as the last was for patients with rare diseases.

Fabry Disease

Gaucher Disease

Patients with Fabry disease are deficient in a particular

enzyme involved in the breakdown of fats, which causes a

buildup of fat in their blood vessels and organs. The symp-

toms of this potentially fatal genetic disorder are diverse

and can make diagnosis difficult.6 They include burning

sensations in the hands and feet, skin rash, excessive

sweating, fever, severe gastrointestinal problems after eat-

ing, and cloudiness of the eye. Fabry disease patients often

survive into adulthood but are at increased risk of strokes,

heart attack and heart disease, digestive problems, and

kidney failure. Fabry disease affects an estimated 1 in

117,000 people, most of whom are male.7,8

PHARMACEUTICAL ADVANCES■ The First to Attack Fabry Disease at Its Root Agalsidase beta, approved in 2003, is the first drug that

treats the cause of Fabry disease rather than lessening its

symptoms. This enzyme replacement reduces the

accumulated fat within the blood vessels and organs

and decreases the symptoms of the disease.9

4

The foods we eat every day are filled with the building blocks of life: carbohydrates, aminoacids, and fats. But to use these materials, the body must break down complex foods intothese simpler, usable forms. Any problems in this process, which is called metabolism, cancause a metabolic disorder, many of which are rare and difficult to treat.

Advances in the Treatment of METABOLIC DISORDERS

Gaucher disease, another rare metabolic disorder, is a

deficiency of the enzyme glucocerebrosidase, which

breaks down and recycles glucosylceramide. The deficien-

cy causes quantities of this fatty substance to accumulate

in the spleen, liver, lungs, bone marrow, and, in rare cases,

the brain.10 This buildup results in bruising, clotting diffi-

culties, fatigue, enlargement of the liver and spleen, weak-

ening of the skeleton, and in some instances, lung and

kidney impairment.

This rare genetic disorder is classified into three differ-

ent types based on clinical severity and course, and by

the presence

or absence of

neurological

complications.

An estimated

6,000 individu-

als in the

United States

have Gaucher

disease.11,12

PHARMACEUTICAL ADVANCES■ Oral Treatment for Patients who Need Another OptionFor patients who cannot receive the standard enzyme

treatment due to allergies, hypersensitivity, or poor venous

access, miglustat, an oral treatment, was approved in 2003for treatment of mild to moderate disease.13 Miglustat

works by reducing the production of glucosylceramide so

that the available glucocerebrosidase enzymes are not

overwhelmed and are able to properly break down the sub-

stance and clear it from the body.14 Miglustat is proven to

decrease the size of the liver and spleen and increase

platelet and hemoglobin levels, which decreases bruising

and fatigue.15

5

Many Symptoms, One Disease

Donna never expected an eye exam would

change her family’s outlook on life. After an

eye doctor noticed clouding in her 8-year-old

daughter’s eyes, Donna and her two sons

were checked for similar symptoms. All four

had corneal opacities. Donna and her chil-

dren were sent to genetic counseling where

doctors confirmed that they had Fabry disease.

Not all Fabry disease diagnoses are as fast as

Donna’s due to the wide variety of symptoms

associated with the disease. Patients with the

disease experience problems ranging from

stomach cramps and vomiting to body aches

and heat intolerance. Another patient,

Adrian, had symptoms that baffled doctors

for years before he was diagnosed. He

eventually visited a rheumatologist who

was able to make sense of his symptoms,

and get him proper medical treatment for

the disease.

Today, Fabry disease patients depend upon

both enzyme replacement therapy (ERT)

and symptom management to manage the

disease. While ERT does not cure Fabry

disease, it can reduce the symptoms of

the disease, giving patients like Donna

and Adrian a second chance at a

normal life.22,23

Between 85 and 90 percent of orphan diseases are seriousor life-threatening.21

Patients with mucopolysaccharidosis VI (MPS VI), also

known as Maroteaux-Lamy syndrome, face many health

problems, which can be devastating depending on the

severity of the disease.

In MPS VI, patients lack a particular enzyme called aryl-

sulfatase B, which breaks down and recycles glycosamino-

glycan (GAG), a complex sugar. GAGs are used to provide

structure for various tissues including bones, cartilage,

skin, and airways. When GAGs accumulate, however, they

can cause a variety of symptoms including thickening of

the nose, lips, and tongue; breathing problems due to

narrowed airways; short stature; frequent ear infections

leading to hearing loss; heart disease as a result of mal-

functioning heart valves, thickening of the heart muscle,

and narrowed blood vessels; and stiff joints.16 Because the

signs and symptoms are so varied, diagnosis is often

difficult and delayed. The disease is also quite rare;

approximately 1,100 people worldwide have MPS VI.17

PHARMACEUTICAL ADVANCES■ First Therapy Targeted Toward Cause of Devastating

Genetic Disorder

Approved in 2005, galsulfase is the first enzyme replace-

ment therapy for MPS VI to treat the cause of the disorder

by breaking down the built-up stores of GAGs instead

of improving symptoms related to the disease.18,19 Because

of the problems associated with the disease, patients with

MPS VI often become tired easily and cannot withstand

long periods of physical activity. In clinical trials, galsulfase

was shown to improve the walking and stair-climbing

capacity of patients.20

Mucopolysaccharidosis VI

Bosentan, the first in a new class of medicines called

endothelin-receptor antagonists, was approved in 2001 for

the treatment of primary pulmonary hypertension to

improve exercise ability and to decrease the rate of disease

progression. Taken orally twice a day, it works by decreas-

ing the stiffness of the blood vessels as well as widening

them to allow blood to flow more easily.28

Treprostinil was approved in 2002 for patients with the

New York Heart Association (NYHA) Class II—IV pulmo-

nary arterial hypertension.29 Heart disease patients are clas-

sified according to the NYHA classification system, which

is based on the capacity of patients with heart diseases to

participate in physical activities, with Class IV disease

resulting in discomfort

with any activity and

symptoms of the disease

occurring even at rest.

In other words, trepros-

tinil treats patients with

moderate to severe PAH,

those who experience

limitations on physical

activity as a result of the

disease. Administered by

continuous infusion, tre-

prostinil works by dilating

the arteries and prevent-

ing blood clot formation.30

Iloprost is the newest medicine for treatment of pulmo-

nary arterial hypertension and was approved in 2004 for

use by patients with NYHA Class III or IV pulmonary

arterial hypertension to increase exercise ability and de-

crease symptoms.31 It is a novel treatment in that it is

inhaled by mouth using a special nebulizer. It works by

dilating the arteries and prevents blood clot formation.32

Pulmonary Hypertension

The pulmonary artery is the blood vessel that carries

blood from the heart to the lungs to be re-oxygenated. In

pulmonary arterial hypertension (PAH) there is continu-

ous high blood pressure in the pulmonary artery. Possible

causes of the increased pressure may include tightened

muscles within the artery walls, thickened walls of the

pulmonary arteries or scar tissue making the arteries

narrower. Tiny blood clots may form within the smaller

arteries and cause blockages. The heart, as a result, must

work harder to supply the body with enough oxygen-rich

blood, and over time the heart muscle weakens.

Shortness of breath is the primary symptom of PAH.

People with PAH might also experience tiredness,

dizziness, chest pain, or a racing pulse. As the disease

progresses, energy level decreases, and these symptoms

can occur even when resting.24

There are two types of pulmonary hypertension: primary

and secondary. Primary pulmonary hypertension is

inherited or occurs for no known reason. Secondary pulmonary hypertension is caused by another condition,

such as chronic heart or lung disease or blood clots in the

lungs.25 According to the American Heart Association, an

estimated 500 to 1,000 new cases of pulmonary hyperten-

sion are diagnosed each year.26 Although this condition is

very rare, four new orphan drugs have been approved to

treat it in the last decade.

PHARMACEUTICAL ADVANCES■ Helping Blood Get to the Lungs

Epoprostenol was approved in 1995 for treatment of

primary pulmonary hypertension. It is an intravenously

administered medicine that works by dilating the arteries,

which allows more blood to flow through the vessel, and

by preventing blood clot formation.27

A person’s blood pressure is continually changing depending on activity, temperature, diet,emotional state, posture, physical state, and medication use. Blood pressure is a measure-ment of the force applied to the walls of the arteries as the heart pumps blood through thebody. It is determined by the force and amount of blood pumped, and the size and flexibilityof the arteries. When any of these factors is compromised, disease may occur.

Advances in the Treatment of RARE BLOOD PRESSURE DISORDERS

6

7

Women with PAH Face Tough Decisions

While both men and women are at risk for pulmonary arterial hypertension (PAH),it is more likely to affect women. Approxi-mately 60 percent of PAH patients hospital-ized between 1995 and 1998 were women.Among those women, 37 percent wereyounger than 65.

Unfortunately, pregnancy aggravates the condition, so for women with PAH, preg-nancy can be life-threatening. Within 35 daysof childbirth, the death rate for new motherswith PAH is between 30 and 56 percent.37

A woman with PAH often must choosebetween having a family and risking herown life to have a baby.

Despite the discouraging statistics,researchers are making progress. A 2001 case study in Chest reported thatepoprostenol therapy combined with ananticoagulant can improve outcomes formother and child when used before, dur-ing, and after delivery, without negativeside effects on the child.38 For nonpreg-nant patients, survival also appears to beincreasing. Many people can managethe disorder for up to 20 years. Geneticstudies and pharmaceutical researchare providing hope for the developmentof new treatments of PAH and possi-bilities for a cure in the future.39

Hypotension is an abnormal condition in which a person’s

blood pressure is lower than it should be. It causes symp-

toms such as dizziness or lightheadedness and inadequate

blood flow to the heart,

brain, and other vital

organs. Orthostatichypotension results from

a sudden change in body

position, usually from

lying down to an upright

position.33 This condition

affects 156,000 people34

and can be caused by

certain medicines,

dehydration, or heart

failure/attack.35

PHARMACEUTICAL ADVANCES

■ Drug Makes Standing Up a Safe Activity

Midodrine hydrochloride is used to treat symptomatic

orthostatic hypotension. It works by stimulating the

blood vessels to tighten, thereby raising blood pressure.

Midodrine was approved in 1996 based on its ability to

increase one-minute standing systolic blood pressure.36

Hypotension

The Orphan Drug Act was enacted in 1983 and encourages companies to develop and manufacturedrugs for rare conditions.

PHARMACEUTICAL ADVANCES■ Finally, Remission and Better Quality of Life for

Those with Painful Bowel Disease

Infliximab, the first therapy for Crohn’s disease, is a

genetically engineered antibody that targets a protein that

promotes inflammation in the body. Administered intra-

venously, infliximab decreases inflammation along the lin-

ing of the intestines and is effective in closing sores

between the bowel and skin.42 In clinical trials, a clinical

improvement or remission occurred in 65 percent of

patients with severe to moderate Crohn’s disease after a

single dose.43 The FDA estimates that this drug can help

about 175,000 people in the United States.44

Imagine needing to run to the bathroom up to 60 times a

day. You might have to get up five times in the middle of

dinner at a restaurant or wake up every 25 minutes in the

night to use the bathroom. Patients with interstitial cystitis(IC) often need to urinate frequently and urgently, and they

may have recurring pain and tenderness in the bladder

and pelvic region.45 These symptoms can disrupt the lives

of patients, making it impossible for 63 percent of them to

work full time.46

These unpredictable symptoms may disappear without

explanation or recur with an event such as a change in

diet, treatment, or menstruation.47 Even when symptoms

disappear, they may return after days, weeks, months,

Crohn’s Disease

Advances in the Treatment of CROHN’S DISEASE & INTERSTITIAL CYSTITIS

8

Interstitial Cystitis

For patients with Crohn’s disease, attacks can bring

everyday activities to a screeching halt as the incurable,

inflammatory bowel disease ravages their gastrointestinal

tract. The 1998 approval of infliximab to treat moderate

and severe Crohn’s was the first therapy approved for the

disease; the compound successfully reduces symptoms

and improves patients’ sense of well-being.40

While scientists are deepening their understanding of the

effects of Crohn’s disease, the cause remains a mystery.

The most popular theory is that the body’s immune sys-

tem reacts to a virus or a bacterium by launching an attack

against the microbes and causing ongoing inflammation

in the intestine. People with Crohn’s disease tend to have

abnormalities of the immune system, but doctors do not

know whether they are a cause or result of the disease.41

Crohn’s disease is characterized by chronic inflammation

of the intestinal wall or any part of the gastrointestinal tract

and causes symptoms of abdominal pain, chronic diarrhea,

loss of appetite, weight loss, joint aches, and fatigue.

Two serious complications are abnormal enlargement of

the colon and intestinal obstruction; the disease also can

cause lesions, abscesses, and grooves in the intestinal wall

and surrounding area.

9

A Decade-Long Struggle with Crohn’s: John’s Story

Diseases can seem especially devastating

when they strike people in their youth. At

age 19, John was diagnosed with Crohn’s

disease. A healthy, active teenager, John

found Crohn’s disease incredibly debilitat-

ing. “My life was on hold—I was not able

to work or go to college for four years.”

Eating became painfully difficult; he says

food felt like broken glass going through

his intestines. Within a month, he had

dropped from 165 to 115 pounds. “I felt

like I was wearing my disease—a disease

no one understood.” After 10 surgeries,

John became “desperate for a solution

that did not include surgery.” That solu-

tion came on his 29th birthday with his

first treatment of infliximab. “It was the

best birthday present I could have ever

received.... I had just about given up

hope, but with this treatment I felt like

I had my life back.”53

or years. Scientists have yet to find the cause of this

disease that affects more women than men. It is most

likely to strike around age 40, but many patients are much

younger. There are 100,000 known cases in the United

States.48

PHARMACEUTICAL ADVANCES■ Soothing the Symptoms of Unpredictable Pelvic

Pain Disorder

Pentosan polysulfate sodium was approved in 1996 and

is the first and only orally administered medicine devel-

oped specifically for relief of IC symptoms. It is believed

that it works by creating a buffer layer on the inside of the

bladder to prevent urine from irritating the bladder wall.49

In clinical trials, the drug was shown to bring relief of

bladder pain to 42 percent of patients who had been

treated for up to six months, and 60 to 62 percent of

those treated for 24 months.50 Patients also experienced

reductions in frequency of urination.51

In the decade after the OrphanDrug Act was passed, there wereabout 10 times as many drugsapproved for rare diseases com-pared with the decade before.52

PHARMACEUTICAL ADVANCES■ First-In-Class Treatment Counteracts Overactive

Parathyroid Glands

Cinacalcet lowers the level of parathyroid hormone

and calcium by increasing the sensitivity of the calcium-

sensing receptor on the surface of the parathyroid gland.56

In doing so, it lowers the risk of altered metabolism of

calcium and phosphorus, bone pain, fractures, and risk for

cardiovascular death. With cinacalcet’s 2004 approval, it

became the first specific pharmaceutical therapy for hyper-

calcemia associated with parathyroid cancer as well as for

secondary hyperparathyroidism.

When a manufactured protein became available in 2003for people with acromegaly, a hormone disorder, it marked

the first in a new class of drugs that block the effect of the

growth hormone. This potentially fatal disease is a result

of the pituitary gland’s producing excess growth hormone.

This excess hormone causes abnormally enlarged hands,

feet, and facial features. Once recognized, acromegaly is

treatable in most patients, but because of its slow and often

insidious onset, it frequently is not diagnosed correctly.57

Hyperparathyroidism

Cinacalcet is the first in a new class of drugs known as

calcimimetics, now available to patients whose parathy-

roid glands (located behind the thyroid gland in the neck)

are producing too much parathyroid hormone. Often, the

cause of hyperparathyroidism is unknown, but in some

cases the overactivity is caused by other conditions, such

as kidney failure or parathyroid cancer. In that case, the

condition is called secondary hyperparathyroidism.

Because they produce excessive parathyroid hormone,

which helps the body absorb calcium from food and

regulates the level of calcium in the blood, hyperparathy-

roidism patients have abnormally high levels of calcium

in the blood (hypercalcemia). Hypercalcemia is associat-

ed with bone pain, fractures, kidney stones, and risk of

cardiovascular death.54 According to the FDA, about

37,000 people in the United States have hypercalcemiaas a result of parathyroid cancer.55

Advances in the Treatment of HYPERPARATHYROIDISM &

10

Acromegaly

11

The “Gentle Giant” with the Devastating Disease

Andre the Giant (born Andres Roussimoff)

built his successful wrestling and acting

career living with acromegaly. Already 6'7"

at age 17, Andre began wrestling as the

“Monster Eiffel Tower” in France. His enor-

mous size, eventually 7'4" and 500 pounds,

jolted Andre to the top of the wrestling

world, with fans dubbing him “The Eighth

Wonder of the World.”

Though he became an international icon as

one of the World Wrestling Federation’s

toughest wrestlers, Andre preferred to

think of himself as a “gentle giant,” like his

character, Fezzik, in The Princess Bride.

Shortly after his death in 1993 due to the

effects of acromegaly, Andre the Giant was

the first wrestler ever inducted into the

WWF/WWE Hall of Fame.63

Today, acromegaly is treatable with

surgery, radiation, and medicines, which

can help normalize levels of growth

hormone and insulin-like growth

factor-1 (IGF-1) in the bloodstream.

There are three drugs available among

three different classes to treat the

condition.64

PHARMACEUTICAL ADVANCES■ Manufactured Protein to Block Growth Hormone

Pegvisomant works by binding to the growth hormone

receptor and blocks the effects of the growth hormone

and reduces the signs and symptoms of the disorder.58

It is indicated for use in patients whose acromegaly has

not responded to surgery, radiation, or other medi-

cines.59 In clinical trials, researchers found that more

than 90 percent of patients responded to the medicine.60

Acromegaly, which is most common in middle-aged

adults, can lead to serious health complications such as

arthritis, diabetes, high blood pressure, and increased risk

of cardiovascular disease. It affects at least 40 to 60 out of

every million people at any time.61

In the pipeline are potentialtreatments for anthrax, cysticfibrosis, and West Nile Virus,which have been granted orphanstatus by the FDA.62

ACROMEGALY

Both neurocysticercosis and hydatid disease are parasitic

diseases from worms and affect approximately 300

Americans annually.71 Neuro-

cysticercosis, caused by pork

tapeworm larvae (eggs), is

usually spread through con-

taminated water or food.

It causes cysts to develop

throughout the body and can

cause headaches and seizures

if they develop in the brain

tissue.72 It is the most common

infectious cause of seizures

worldwide.73

People can contract hydatid disease, also known as

Echinoccocus, by eating contaminated food containing

Echinococcus granulosus worm eggs. The infection causes

cysts in the liver first but they can also develop in the

lungs, brain, bones, and other organs. If the cysts rupture,

severe illness results, including fever, low blood pressure,

and shock.74,75

PHARMACEUTICAL ADVANCES■ First Treatment for Two Kinds of Cyst-Causing Worms

In 1996, albendazole became the first treatment approved

to treat both neurocysticercosis and hydatid.76 Albendazole

kills the worm by preventing it from absorbing sugar (glu-

cose), which it needs to survive.77 This drug was found to

destroy cysts in 40 to 70 percent of patients with neurocys-

ticercosis. Among patients with hydatid disease, albenda-

zole eliminates the cysts in about 30 percent of patients

and reduces their size in an additional 40 percent

of patients.78

Cryptosporidiosis and Giardiasis

Cryptosporidiosis and giardiasis, parasitic infections that

cause diarrhea, mainly affect people living in developing

countries around the world, but even in the United States

there are cases every year.65

The parasite cryptosporidium can be found in drinking or

recreational water and contaminated food. Once it enters

the body it lives in the intestinal tract, but outside the body

it can survive for long periods because of a tough outer

shell. The parasite causes vomiting and nausea, dehydra-

tion, stomach pain, and weight loss.66 Giardiasis is an

infection caused by a single-celled parasite called Giardialamblia or, simply,

Giardia. If left

untreated in children,

complications from

these parasites

include malnutrition,

impaired growth,

and death.67

PHARMACEUTICAL ADVANCES■ Killing Parasites That Cause Dangerous

Waterborne Illnesses

Nitazoxanide, an antiprotozoal approved in 2002, is used

to treat children up to 11 years of age with diarrhea caused

by cryptosporidiosis and giardiasis. It is the first new drug

approved for giardiasis in over 40 years.68 Nitazoxanide is

the only drug approved for treating cryptosporidiosis and

the only drug approved for giardiasis for children one to 11

years of age. Nitazoxanide works by stopping the growth of

the infecting organisms.69 The FDA estimates that nitazox-

anide could help 2,500 people in the United States.70

Advances in the Treatment of DISEASES OF THE DEVELOPING WORLD

12

Neurocysticercosis and Hydatid

Some diseases considered rare in the United States are actually very common around theworld. For these diseases, new treatments being developed in the United States are helpingmillions of men, women, and children in the developing nations. Even before the horrors ofHurricane Katrina spotlighted waterborne hazards, here in the world’s wealthiest nation,handfuls of Americans have been affected every year by outbreaks of illnesses that are leadingcauses of death in developing countries.

13

Tuberculosis—A Disease from Antiquity

Tuberculosis has ravaged human culture

since ancient times. Egyptian mummies

tell the story of deadly tuberculosis infec-

tions thousands of years ago. Fragments

of the spinal columns of mummies

dating back to 2400 B.C. show evidence

of damage caused by the bacteria. Later,

around 460 B.C., Hippocrates wrote

that tuberculosis was the most wide-

spread disease of the time in Greece

and was nearly always fatal.84 Today,

tuberculosis infections still occur in

all parts of the world, but mankind is

fighting back. Scientists are using the

vast knowledge and powerful tools

that the Egyptians could not have

dreamed of to develop new treat-

ments for this age-old foe.

Tuberculosis (TB) is still the most common cause of death

and morbidity in the world, killing 30 million people

worldwide in the 1990s, according to the WHO.79 In the

United States, fortunately, it is a rare condition affecting

just 15,000 people in 2003.80

TB is a contagious bacterial infection that primarily affects

the lungs but can attack any part of the body. It is caused

by Mycobacterium tuberculosis and is typically spread

through the air from a cough or sneeze of someone who is

infected with the bacteria. If not treated properly, TB can

be fatal.

PHARMACEUTICAL ADVANCES■ Modern Treatment for Ancient “Consumption”

In 1998, the first new drug to treat TB in 25 years,

rifapentine, was approved for treatment of pulmonary

tuberculosis. It works by stopping the cell multiplication

process of the bacteria and is used in combination with

other anti-tuberculosis drugs to treat pulmonary tuberculo-

sis.81 Before rifapentine was approved, the health care com-

munity was worried about resistance to older drugs that

was developing over time. This treatment offers another

tool to fight tuberculosis. Also, the dosing regimen for this

drug is simpler than other drugs, so patients are more

likely to take it.82

Tuberculosis

In the last decade (1995–2005),over 160 orphan drugs wereapproved, compared with 108from 1984 to 1994 and only 10 inthe decade prior to the passage ofthe Orphan Drug Act in 1983.83

Thrombocytopenia

Thrombocytopenia is caused by too few platelets in the

blood, which are responsible for forming clots along with

clotting factors if damage occurs to the blood vessels.

Patients with this disorder bleed even with minor injuries,

and in severe cases with no injury at all. This deficiency

of platelets can be caused by a few factors, including low

platelet production by the bone marrow, infection, other

diseases, or sometimes drugs.85 Heparin, a drug used to

prevent blood clots and to “thin” blood by inhibiting clot-

ting factors in situations such as acute coronary syndromes

including heart attacks, can cause thrombocytopenia in

some patients.86

PHARMACEUTICAL ADVANCES■ Alternative Blood-Thinning Treatment

In 1998, lepirudin was introduced as the first alternative

to heparin for patients who experience heparin-induced

thrombocytopenia. Lepirudin is a derivative of the saliva

of a medicinal leech, a bloodsucking aquatic worm that

is sometimes used in blood withdrawal. Lepirudin

blocks thrombin, which is an enzyme that aids in clot

formation. Lepirudin also promotes a rapid increase of

platelets.87 The FDA estimates that 180,000 people

could benefit from this new drug.88

Advances in the Treatment of BLOOD DISORDERS &

14

Hemophilia B

Our bodies depend on small, specialized cells that make up blood to transport nutrients,gases, and waste products throughout our bodies. An imbalance of too many or too fewspecific cells can cause illnesses. Today’s pharmaceutical innovations, however, are revolu-tionizing treatments for people with rare blood diseases.

Hemophilia B is a rare congenital disorder caused by

the lack of clotting Factor IX, a type of protein that works

with platelets to form clots when damage to a blood vessel

occurs. Hemophilia B affects approximately 18,000

Americans.89 People with this disease bleed excessively

and for longer than other people. It can be life-threatening.

PHARMACEUTICAL ADVANCES■ DNA-Derived Clotting Factor: A Better Treatment

Option for Patients

Recombinant human Factor IX was approved in 1997for the prevention and control of excessive, potentially

life-threatening bleeding in hemophilia B patients.

Recombinant DNA-derived clotting factors are lab-

produced using Chinese hamster ovary cells that have

been modified to express the human Factor IX gene.90 The

advantage of recombinant human Factor IX over other

sources of Factor IX is that it is free from the risk of

transmitting human viruses.

15

Leprosy—RLeprosy—Reason for Exile ineason for Exile inthe Old Wthe Old Worldorld

Tales of leprosy date back to biblical times.

During those times, leprosy was thought to

be transmitted by contact with infected

people. To decrease the possibility of catch-

ing the disease, leprosy sufferers were

often shunned. “…[I]n Europe during the

Middle Ages, leprosy sufferers had to wear

special clothing, ring bells to warn others

that they were close, and even walk on a

particular side of the road, depending on

the direction of the wind. Even in mod-

ern times, leprosy treatment has often

occurred in separate hospitals and live-in

colonies called leprosariums because of

the stigma of the disease.”98 However,

new medicines continue to combat

leprosy infections, and the number of

known cases is falling.

Leprosy is an infectious disease caused by the bacteria

Mycobacterium leprae with symptoms of disfiguring skin

lesions and sensory loss in the skin, muscle weakness, and

progressive debilitation caused by peripheral nerve dam-

age. Symptoms can take as long as 20 years to develop.

Through ancient times, leprosy was regarded by the com-

munity as a contagious, mutilating and incurable disease.

Today, leprosy is treatable and curable, and we now know

it is difficult to transmit.91,92

While leprosy is most common in temperate, subtropical

and tropical climates, approximately 100 cases are diag-

nosed each year in the United States. Children are more

susceptible than adults to contracting the disease.93

Erythema nodosum leprosum (ENL) is a serious inflam-

matory complication of leprosy that can include severe

skin lesions, nerve pain, loss of nerve function, joint

swelling and high fever.94

PHARMACEUTICAL ADVANCES■ Ancient, “Incurable” Disease Now Treated with

“Second Chance” Drug

Nearly 40 years after thalidomide was first found to pro-

duce severe birth defects when used as a treatment for

morning sickness associated with pregnancy in coun-

tries around the world, it was approved for the first time

by the FDA in 1998. With tight restrictions, it is now

used to treat debilitating skin sores that result from

ENL.95 In clinical trials, treatment with thalidomide

caused improvement in at least 70 to 80 percent of

patients with ENL, compared to approximately 25 percent

of patients given placebo.96

Leprosy

Since the Orphan Drug Act,over 1,450 drugs in developmenthave been designated as orphanproducts.97

LEPROSY

Poractant alfa, approved in 1999, treats RDS in premature

babies by reducing the amount of air trapped in the lining

of the lungs. A natural porcine-derived surfactant, porac-

tant alfa increases lubrication within the lung’s air sacs

thus improving expansion and ventilation.104

Children with the genetic, metabolic disorder tyrosinemiagradually develop liver failure and liver cancer, but a new

drug, nitisinone, approved in 2002, can extend their lives.

These children lack the enzyme that breaks down the

amino acid tyrosine. Normally, the liver is where tyrosine

is broken down; when it accumulates in the blood, it can

lead to progressive liver failure and, often, cancer.

Tyrosinemia may also cause damage to the kidneys, eyes,

skin, and nervous system.

The most common and severe form of the disease is acute

tyrosinemia, with which children are born or develop soon

after birth. Infants with acute tyrosinemia exhibit rapid

onset of symptoms, and they often fail to gain weight and

grow. Infants with the less prevalent chronic tyrosinemia

have a more gradual and less severe onset of symptoms.

Children who experience liver failure or are diagnosed

with liver cancer as a result of tyrosinemia rarely make it

into their twenties without a liver transplant. According

to the FDA, this disorder affects 2,500 children in the

United States.105

PHARMACEUTICAL ADVANCES■ Patients’ Pathway to Longer Life

Nitisinone opens the door to an extended lifespan for chil-

dren with tyrosinemia. It decreases the level of tyrosine

in the blood, thereby reducing the likelihood of liver

failure and liver cancer. In combination with a diet restrict-

ed in the amino acids tyrosine and phenylalanine, this

drug has been shown to increase the four-year survival

rate of children who were diagnosed at less than two

months of age to 88 percent. Historical data for children

treated with dietary restrictions alone shows a survival

rate of 29 percent for the same time period.106

Respiratory DistressSyndrome

Premature babies face an uphill battle as their fragile,

still-developing systems fight to overcome many issues—

including immature lungs struggling just to breathe.

Respiratory distress syndrome (RDS) is caused by an

infant’s lack of surfactant, a natural lung-wetting agent,

which normally develops between the 34th and 37th week

of pregnancy. Without surfactant, the lungs cannot in-

flate.99 Its absence in premature infants causes breathing

difficulties and collapsed lungs. Prompt treatment is

required for high-risk and premature infants. This treat-

ment may include medicines, supplemental oxygen, and

use of a ventilator.100

Of the 250,000 infants born prematurely each year, up to

50,000 will suffer from infant RDS, and 5,000 will die

from it.101 RDS usually occurs right after birth.

Three new medicines have been approved in the last decade

for this one rare condition,

advancing the way that

neonates with immature

lungs are treated. With

these medicines, prema-

ture infants have a better

chance of surviving this

life-threatening disorder.

PHARMACEUTICAL ADVANCES■ Rescuing the Tiniest Lungs

Calfactant, approved in 1997, is used to treat babies with

RDS, and also to prevent premature babies from develop-

ing RDS.102 A natural bovine-derived surfactant, calfactant

attaches rapidly to the surface of the air-to-liquid inter-

face within the lung’s air sacs and modifies surface

tension similarly to natural lung surfactant, thereby

allowing the air sacs to expand and improving newborns’

breathing ability.

Nitric oxide, approved in 1999, reduces the common com-

plications of lung hypertension in newborns by expanding

blood vessels in the lungs.103 Nitric oxide reduces the need

for ventilator support and helps regulate the muscle tone

in the arteries of the lungs.

Advances in the Treatment of CHILDHOOD DISEASES

16

Tyrosinemia

17

Hope is in the Pipeline forChildren with Progeria

Medical researchers are racing to beat the

clock in search of a cure for progeria, a

premature aging condition that afflicts just

14 children in the United States and

usually leads to death near age 13. In 2003,

scientists were able to isolate the gene

mutation that causes this rare disease. In

2004, researchers were able to explain

how the gene mutation works.112 Now,

NIH scientists and others are testing a

group of cancer drugs donated by phar-

maceutical companies. These drugs

appear to repair cells damaged due to

the disease. By halting the rapid aging

process associated with the disease and

restoring damaged cells, medical

research gives children living with

progeria hope that their time will not

run out before they reach adulthood.113

Primary IGF-1 Deficiency

The number of orphan drugs is expected to rise in the comingyears as more new medicines aredeveloped that target specificgenetic disorders.111

Kids labeled as having “short stature” are shorter than

97.5 percent of other children their same age and gen-

der. Short stature can be caused by several factors,

including family genetics, hormone problems, or

various diseases.107

Recently, it has been found that

short stature can also be the

result of low insulin-like

growth factor-1 (IGF-1) levels.

This condition is called

Primary IGF-1 Deficiency(Primary IGFD). If left

untreated, Primary IGFD

can lead to other complications

such as lipid disorders, obesity,

diabetes, or decreased

bone density.108

PHARMACEUTICAL ADVANCES■ First Medicine to Treat Primary IGFD

In 2005, the FDA approved mecasermin, the first treat-

ment for approximately 6,000 children in the United

States with severe Primary IGFD.109 Mecasermin is a

manufactured protein that functions like the natural

human protein as a growth catalyst. This protein must

be present for children’s bones, cartilage, and organs to

grow properly. An eight-year clinical trial demonstrated

that, on average, children grew one inch per year for

each year of therapy using this new medicine.110

Currently, there is no medicine available that allows

narcolepsy patients to maintain a normal level of aware-

ness consistently, but some of the most severe symptoms,

such as EDS and cataplexy, can usually be controlled with

medications.118

The cause of narcolepsy remains unknown,

but genetic factors may play a role.119


■ Easing Worst Symptoms of Sleep Disorder

Modafinil was approved in 1998 for the treatment of

narcolepsy and is the first new stimulant for treatment in

the last 20 years. Modafinil promotes wakefulness without

affecting memory, concentration, or learning.120 It also has

a lower habituation potential than other stimulants that

are often used for treatment of narcolepsy.121 In clinical

trials, modafinil proved to be effective in alleviating EDS

while producing fewer, less serious side effects than

other medications.122

Sodium oxybate is the first approved treatment for cata-

plexy. Available since 2002, it reduces the number of

cataplexy attacks,123 which can cause a patient’s muscles

to feel weak or paralyzed.

Amyotrophic lateral sclerosis (ALS), also known as LouGehrig’s Disease, is a progressive disease that affects

motor nerve cells in the brain and spinal cord. Motor

neurons degenerate and eventually die, causing the brain

to lose its ability to control muscle movement. The pro-

gressive loss of muscle strength and coordination

eventually interfere with the ability to perform routine

activities, such as going up steps, swallowing, or rolling

over. Eventually it leads to death, often because it affects

the muscles needed for breathing. ALS, however, has no

effect on a person’s ability to think or reason.124 It is usually

fatal within five years of diagnosis.125

Narcolepsy

Advances in the Treatment of NARCOLEPSY &

18

In people with narcolepsy the brain does not properly

regulate sleep and wake cycles, so they experience episodes

of frequent, uncontrollable daytime sleeping. It is

estimated that narcolepsy, which is generally a lifelong

condition, affects 135,000 people in the United States.114,115

For these patients, falling asleep in unlikely situations is

much more than an inconvenience; it can jeopardize

their education, ruin relationships, or endanger their

lives when driving.

Excessive Daytime Sleepiness (EDS) is the most common

symptom of narcolepsy patients, but they can also have

cataplexy (sudden loss of muscle tone), sleep paralysis

(temporary inability to use muscles), and hallucinations

before and/or after sleep episodes.116 A cataplexy episode is

often triggered by emotions such as surprise or anger,

causing a range of effects, from a simple slumping of

the head or a more dramatic collapse of the body. An

estimated 20,000 to 50,000 narcolepsy patients

experience cataplexy.117

ALS/Lou Gehrig’s Disease

19

An “orphan” or rare diseaseaffects fewer than 200,000 people in the United States.131

Symptoms usually do not develop until after age 50. In

about 10 percent of cases, ALS is caused by a genetic

defect. In other cases, the cause of the nerve deterioration

is unknown.126 ALS affects approximately 30,000 people in

the United States, and about 5,000 new cases are

diagnosed each year.127


■ Breakthrough Treatment a First After 126 Years

ALS was first identified in 1869, but the first drug,

riluzole, was not approved for treatment until 1995. It is

the first drug to show any increase in survival for ALS

patients.128 The increase is a modest three months on

average, but it offers hope.129 The drug is based on a theory

that the disease is caused by toxic levels of glutamate in

the brain. Neurons in the central nervous system use

glutamate to communicate with one another. The brain

normally regulates glutamate levels, but glutamate has

been found at abnormally high levels in the cerebrospinal

fluid of some ALS patients. Scientists theorize that gluta-

mate toxicity might be killing motor neurons, leading to

progressive muscle degeneration in people with ALS.

Riluzole, however, inhibits the release of glutamate in

the brain.

According to Dr. Jeffrey Rothstein of Johns Hopkins

University School of Medicine, this medicine offers great

hope despite the fact that the improvement is not dramatic:

“This is against the background of decades when no drug

ever did anything for the disease. Initial therapies for

many diseases, like leukemia and other cancers, had the

same kind of effect... a modest increase in survival. But

they were followed by better therapies that, over time,

increased patients’ survival…. It’s a daunting task, but I

envision that someday it will be possible to develop drugs

that will not only stop motor neurons from dying but

replace them and reverse the course of ALS.”130

AMYOTROPHIC LATERAL SCLEROSIS

A PA Pitch for ALSitch for ALS

Sixty-five years after baseball legend Lou

Gehrig announced his battle with ALS to

the world, Red Sox pitcher Curt Schilling

brought the disease back to international

attention. During game two of the 2004

World Series, Schilling, pitching with an

injured ankle, wrote “K ALS,”meaning

strikeout ALS, on his shoe, just below his

blood-stained sock. Photographers looking

to capture images of an athlete persever-

ing through pain instead told the story of

a man fighting for the 30,000 Americans

living with ALS.

Curt Schilling is the pitcher for the 2004World Series Champion Boston Red Sox. He and his wife, Shonda, becameinvolved in the fight against ALS aftermeeting Dick Bergeron, an ALS patient,in 1992.

medication in the comfort of their own homes rather

than having to receive intravenous treatments at a physi-

cian’s office or hospital.

■ Dual-Action Therapy Initiates Immune Responseand Attacks Tumor Cells Directly

Non-Hodgkin’s lymphoma is a cancer of lymphatic

tissues, such as lymph nodes, spleen, and other immune

system organs. There are several different types of non-

Hodgkin’s lymphomas. One of those types, follicular

lymphoma, makes up 22 percent of all non-Hodgkin’s

lymphomas. Follicular lymphoma is not curable, but

due to its slow growth, 60 to 70 percent of patients live

at least five years; it occurs mainly in adults, with an

average age of 60.141 People with follicular non-Hodgkin’s

lymphoma usually have lymphoma in many parts of the

body. According to the FDA Office of Orphan Products,

the condition affects 193,500 people in the United States.

With the 2003 approval of tositumomab and Iodine-131tositumomab, patients with a subset of follicular non-

Hodgkin’s lymphoma—CD20 positive follicular non-Hodgkin’s lymphoma—gained a new treatment option

with an innovative therapeutic twist. The drug is made up

of an immune system protein, called an antibody, attached

to radioactive Iodine-131. Combined, they form a “radiola-

beled” monoclonal antibody that is able to bind to a

protein found only on the cancer cells, thus targeting the

radioactivity directly

to the cancer cell,

killing it.142,143

This new medicine is

used for patients with

CD20 positive follicu-

lar non-Hodgkin’s

lymphoma who have

not responded to

other treatments or

whose cancer has

returned after

chemotherapy.144 For

more than two years,

Cancer

Cancer is a group of diseases in which abnormal cells

develop and spread through parts of the body. Anyone can

develop cancer. The National Cancer Institute estimates

that 9.8 million Americans with a history of cancer were

alive in 2001. Some were cancer-free; others were continu-

ing to undergo treatment.132


■ Disrupting DNA Adds Months for Severe Brain Cancer Patients

In the two most aggressive forms of astrocytoma, brain

tumors grow rapidly and spread to other parts of the body.

Astrocytoma is classified into four grades (Grade I being

the least aggressive and IV most aggressive). Grade III

is anaplastic astrocytoma, which affects 2,000–3,000

people a year with an average survival of two to three years.

Grade IV is glioblastoma multiforme, which affects

8,000–10,000 people each year and is usually fatal within

one year.133

Temozolomide can add an average of two and a half addi-

tional months—an enormous amount of time in the world

of cancer treatment—for patients with glioblastoma

multiforme.134,135 “It doesn’t sound like much… but if you

can demonstrate that you can extend life for two or three

months for the average patient, that’s a significant

advance,” says Dr. Warren Mason, the co-author of a

New England Journal of Medicine study about the drug.136

Patients taking temozolomide for treatment of anaplastic

astrocytoma experienced an average survival time of nearly

16 months.137

Approved in 1999, temozolomide is the first major new

treatment for anaplastic astrocytoma in 20 years, and with

a second indication approved in 2005, it is the first in over

30 years for glioblastoma.138,139 It works by disrupting DNA

to prevent cancer cells from multiplying and prolongs

survival when combined with standard radiation.140

Additionally, it is a more convenient therapy for patients;

it is an oral treatment allowing patients to take their

Finding treatments for rare cancers at specific stages for patients unresponsive to existing treatment might be the toughest—and most gratifying—work a scientist could ever attempt.

Advances in the Treatment of CANCER

20

21

There are approximately6,000–7,000 rare diseases.149

Thankful for Another Day

Karl, like many people, was not one to visit

his doctor often, even if he was feeling

under the weather. However, after days and

days of feeling tired and eventually having

difficulty just getting in and out of the car,

Karl decided it was time to see a doctor.

After an x-ray and other tests, he was diag-

nosed with mesothelioma. Karl’s daughter,

who works in a hospital, was familiar with

the disease and understood the prognosis

was poor. Fortunately, after several chemo-

therapy treatments with pemetrexed,

Karl’s condition began to improve. Karl’s

wife is thankful, noting, “Every day, we

are both thankful for our lives. And, he

is improving every day and he is doing

more and more: He is in the yard, or we

are going shopping together, or we can

drive in town together. He could not

drive before. Now, little by little, it’s

getting better and better and we are

very grateful for that.”150

on average, two-thirds of patients who took this medica-

tion during clinical trials experienced either improved

condition or full remission of the disease.145

■ First Ray of Hope for Asbestos-Related Lung Cancer

When someone first experiences symptoms and is diag-

nosed with malignant pleural mesothelioma, the fatal

cancer is often already in advanced stages, and doctors

expect them to live just nine to 13 months.146 Malignant

pleural mesothelioma is a cancer of the lining of the lung

and chest cavity, called the pleura. This is a very rare type

of cancer affecting only 2,000 new people each year, and it

is associated with exposure to asbestos.

Now the first drug approved for this rare cancer,

pemetrexed, combined with other treatments, gives

patients 40 percent longer survival time compared with

current treatment alone. “Before [pemetrexed] was

available, patients suffering from mesothelioma had no

hope—rarely living a year after diagnosis,” said

Nicholas J. Vogelzang, MD, Director of the Nevada

Cancer Institute in Las Vegas. “At 18 months, there is

still a statistically significant difference in survival, which

demonstrates patients are living longer when treated with

this [pemetrexed] combination,” Volgelzang said.147

Approved in 2004, pemetrexed is a novel antifolate, a class

of drugs that targets the folic acid metabolic pathway,

which affects availability of certain B complex vitamins.148

It is indicated for patients with the advanced form of the

disease who have already had chemotherapy. Pemetrexed

was found in clinical trials to be as effective as other can-

cer drugs, but with fewer side effects, such as hair loss and

subsequent infections.

Leukemia

In leukemia, the bone marrow produces abnormal white

blood cells—the leukemia cells, which in time may crowd

out normal white blood cells, red blood cells, and platelets.

Types of leukemia vary according to which type of blood

cells are affected, how developed the cancer cells are at the

time of diagnosis, and how different they are from normal

cells.151 According to the National Cancer Institute, there

were 30,600 new cases of leukemia in the United States

in 2003.152


■ Ancient Medicinal Offers New Hope to Young Adults

Contrary to images people may conjure up when hearing

“arsenic,” it actually has given new hope to patients with

acute promyelocytic leukemia (APL), which is most com-

mon in young adults and causes fatigue and tendency

to bleed. Arsenic-containing preparations, dating back

more than 2,000 years, were used more than 100 years

ago for leukemia therapy but were replaced by modern

chemotherapy. Because

some Chinese arsenic-

containing treatments

showed effectiveness

against leukemia,

attention again turned

to arsenic.”153

Arsenic trioxide was

approved in 2000 to

treat APL patients whose

disease has recurred or

failed to respond to stan-

dard treatment (about

400 of the 1,500 diagnosed cases per year).154 About 75

percent of APL patients can be cured with other combina-

tion therapies, but those who do not achieve remission or

who relapse can now be treated with arsenic trioxide.155

■ From Texas Soil to New Class of Anticancer Therapy

The story of gemtuzumab began with a soil sample

gathered in Kerrville, Texas, in 1981 and finally burst to the

forefront of oncology in 2000 as the first in a new class of

drugs, “antibody-targeted chemotherapy.” Scientists study-

ing the soil discovered a powerful cancer-fighting substance,

calicheamicin, which destroyed the DNA of cancer cells

and proved to be stronger

than any anticancer drugs

at the time. But it was up

to 10,000 times more toxic

to normal cells than other

anticancer drugs. Research-

ers discovered that by

attaching calicheamicin to

an antibody (immune

system protein), they could

safely bring it directly to

the tumor, bypassing most

normal cells. In May 2000, the FDA approved the first

antibody-targeted chemotherapy, gemtuzumab, for use

in patients over age 60 with relapsed acute myeloidleukemia (AML).

In patients with AML, unhealthy white and red blood cells

and platelets build up in the bone marrow, blood, and

other parts of the body leading to infections, easy bleeding,

and anemia. AML quickly worsens if not treated.156 It is

estimated that in 2005, 11,960 cases of AML will be diag-

nosed and will cause 9,000 deaths.157 Gemtuzumab was

found to cause remission in about 30 percent of AML

sufferers and produces fewer side effects than traditional

chemotherapies.158

■ A Powerful Attack and a True Trailblazer

The approval of imatinib mesylate in 2001 proved that a

targeted therapy—one that directly turns off the signal of a

protein known to cause cancer—could powerfully attack

cancer with few side effects.159 Imatinib not only benefits

patients with chronic myeloid leukemia (CML), but its

success proves that the targeted therapies scientists

dreamed of do work. With this proof-of-concept, scientists

may be able to create strong, effective targeted therapies

22

Thanks to advances in pharmaceutical treatment and other research, the survival rate ofpeople with leukemia has tripled in the last 40 years.

Advances in the Treatment of LEUKEMIA

23

The Wave of the Future Brings Hope

A new generation of precise and powerful

drugs known as “targeted therapies” may

represent a better way to treat many cancers,

bringing hope for patients with rare cancers.

Leukemia treatments are blazing the trail.

“Slowly, many scientists believe, the drugs are

transforming cancer treatment. But for now,

the drugs are still only a whisper of hope.

They are not a miracle cure and not fully

understood. Many are still in clinical trials.

Those that work often help patients in sub-

sets of disease—one kind of leukemia, one

type of breast cancer…

“Yet for all they are not, it is what the drugs

achieve for the lucky few that captures the

imagination: the stories that patients tell of

teetering near death, only to see a stunning

comeback, at least for a while. They can

mean an extra three months or five

months or a year—another Christmas

with the family, another season to plant a

garden, another passage in the life of a

child. Side effects, the bane of cancer

treatment, are comparatively few.”167

— Donna St. George,

The Washington Post

One in every 10 individuals inthis country has received adiagnosis of a rare disease.166

for other cancers. Clinical trials showed imatinib’s

remarkable efficacy, as most patients receiving the new

drug were experiencing complete normalization of their

blood counts.160

In patients with CML, the bone marrow produces too

many stem cells which develop into a type of white blood

cell called granulocytes. Some of these cells never become

mature white blood cells; these are called blasts. Over

time, the granulocytes and blasts crowd out the red blood

cells and platelets in the bone marrow. CML usually

occurs in middle-aged or older adults.161 It is estimated

that 4,600 new cases of chronic myeloid leukemia will

be diagnosed this year, and 850 people will die from

the disease.162

■ First For-Kids-Only Leukemia Drug in 10 Years

For 10 years, oncologists treating pediatric patients with

acute lymphoblastic leukemia (ALL) treaded water as ther-

apy for the most common childhood leukemia had hit a

plateau.163 Finally, the 2004 approval of clofarabine pre-

sented a new option for children aged 1 to 21 with ALL

who had relapsed or were unresponsive to other treat-

ments. Clofarabine produces remissions and allows some

patients to proceed to bone marrow transplant, the best

chance for long-term survival.164

About 3,830 Americans are diagnosed with ALL, the most

common type of leukemia in patients under age 19, each

year.165 In ALL, abnormal blood cells called lymphoblasts

accumulate, while fewer normal red and white blood cells

are produced.

Clofarabine is an antimetabolite, a drug that prevents can-

cer cells from growing by disrupting the synthesis of

nucleic acids, which are needed to produce DNA and RNA.

Conclusion

Looking back over the last decade, we have clearly made

much progress and because of these new treatments many

lives have changed. These facts offer hope to the many

patients with rare diseases who are still waiting for treat-

ments. Looking forward, the future holds great promise.

Just as the number of new orphan drugs being approved

has grown, the number currently being studied continues

to rise. According to the FDA’s Office of Orphan Products

Development, in 2004 there were a record 160 applications

24

for orphan status among drugs in development. That

number represented a 30 percent increase over the average

of 124 per year in the previous four years.168

Pharmaceutical discovery is entering a new era. Our

new understanding of the genome and powerful scientific

research tools are opening new doors to discovery of

breakthrough medicines. The number of orphan drugs

is expected to rise in the coming years as more new medi-

cines are developed that target specific genetic disorders.169

Progress has been made in the last decade, but the work

continues. Biopharmaceutical companies are working tire-

lessly so that more patients with rare diseases will have

new treatments one day soon.

LOOKING BACK…

In the past year alone, nine new orphan drugs were

approved. These new medicines that provide additional

treatment options for a variety of diseases include:

• Nelarabine—For patients with T-cell acute lympho-

blastic leukemia and T-cell lymphoblastic lymphoma,

this new treatment resulted in complete disappear-

ance of cancer cells in some patients during clinical

trials. 170

• Deferasirox—The first oral therapy for chronic iron

overload, it allows patients to drink their medicine

rather than endure multi-hour nightly infusions to

remove excess iron.171

• Sorafenib tosylate—The first new treatment for kid-

ney cancer in 12 years, it extended time until tumor

progression and until death in patients with this

rare cancer.172

• Lenalidomide—This is an oral treatment for patients

requiring blood transfusions as a result of anemia

caused by myelodysplastic syndrome, which causes

low red blood cell counts. Patients who received this

medicine during clinical trials no longer needed

blood transfusions.173

25

LOOKING AHEAD…

Every day researchers continue to search for and develop

new medicines for rare diseases. Here are examples of the

many potential orphan drugs that scientists currently are

working on:

• Dasatinib—This new compound, currently in review

with the FDA, builds on the success of the first tar-

geted cancer treatment, imatinib. Dasatinib is being

tested as an alternative to treat patients with chronic

myeloid leukemia. One clinical study found 95 per-

cent of patients had progression-free survival in the

first six months.175

• Anti-GDF-8 antibody/MYO-029—Currently in early

clinical trials, this recombinant human antibody

(immune system protein) is being tested to treat

muscular dystrophy (MD) and other muscle-wasting

diseases.176 It is designed to inhibit the protein myo-

statin, which limits muscle growth,177 and it would be

the first treatment to halt the breakdown of muscle

in MD.178

• FK778—The first in a new class of drugs to help

prevent acute rejection after kidney, heart and

liver transplants. FK778 is now in Phase II clinical

trials,179 and to this point, tests indicate that it may

treat both short- and long-term problems that

accompany organ transplantation.180

Amyotrophic Lateral Sclerosis (ALS) 5

Pulmonary Hypertension 6

Interstitial Cystitis 3

Acromegaly 2

Tuberculosis 5

Thrombocytopenia 5

Mesothelioma 9

Acute myeloid leukemia 31

New Medicinein Clinical Trialsor FDA Review

Disease

Medicines in Development forSelected Rare Diseases174

26

1 Food and Drug Administration, Office of Orphan Products

Development, “List of All Approved Orphan Products Through

the Year 2005,” 13 May 2005, http://www.fda.gov/orphan/

designat/allap.rtf (accessed 7 September 2005).

2 National Institutes of Health, Office of Rare Diseases, Biennialand Annual Report on the Rare Diseases Research Activities at theNational Institutes of Health FY 2004, Executive Summary

(Bethesda, MD: NIH, 22 July 2005), http://rarediseases.info.

nih.gov/html/reports/fy2004/summary04.html.

3 National Institutes of Health, Office of Rare Diseases, Access toQuality Testing for Rare Diseases: A National Conference,Overview (Rockville, MD: NIH, 26 September 2005),http://rarediseases.info.nih.gov/QTRD/overview.html.

4 National Organization for Rare Disorders, http://www.

rarediseases.org (accessed 11 August 2005).

5 Food and Drug Administration, “Office of Orphan Products

Development,” Budget 2006, http://www.fda.gov/oc/oms/

ofm/budget/2006/PDFs/Summary/Pages194thru199.pdf

(accessed 7 September 2005).

6 Fabry Community, Health Care Professionals, http://www.

fabrycommunity.com/healthcare/fc_p_hc_overview.asp


7 National Institute of Neurological Disorders and Stroke, “NINDS

Fabry’s Disease Information Page,” National Institute of Neurolo-gical Disorders and Stroke, http://www.ninds.nih.gov/disorders/

fabrys/fabrys.htm (accessed 12 May 2005).

8 Fabry Community, Fabry Disease Overview, http://www.

fabrycommunity.com/patient/about/fc_p_pt_fabry-disease.asp

(accessed 12 May 2005).

9 S. Reents et al., Clinical Pharmacology, Gold Standard Multi-

media, Inc., Fabrazyme®, http://cp.gsm.com (accessed 10 May

2005).

10 National Institute of Neurological Disorders and Stroke, “NINDS

Gaucher’s Disease Information Page,” National Institute ofNeurological Disorders and Stroke, http://www.ninds.nih.gov/

disorders/gauchers/gauchers.htm (accessed 12 May 2005).

11 National Tay-Sachs and Allied Diseases Association, Inc.,

Gaucher Disease, http://www.ntsad.org/pages/gaucher.htm


12 National Organization for Rare Disorders, Gaucher Disease,http://www.rarediseases.org/search/rdbdetail_fullreport_pf

(accessed 30 August 2005).

13 National Gaucher Foundation, Prevention and Treatment ofGaucher Disease, http://www.gaucherdisease.org (accessed 12

May 2005).


media., Inc., Zavesca®, http://cp.gsm.com (accessed 10 May

2005).

15 Actelion Pharmaceuticals US Inc., “Balance at Work in Patients

Naive to ERT,” Zavesca, http://www.zavesca.com/HP_PNE.html


16 The National MPS Society, A Guide to Understanding Maroteaux-Lamy Syndrome, http://www.mpssociety.org/images/pdfs/

booklets/MPS%20VI%20final.pdf (accessed 29 September

2005).

17 MPSVI.COM, http://www.maroteauxlamy.com/pc/faq/faqs.asp


18 CenterWatch, Naglazyme, http://www.centerwatch.com/cgi-bin/

cl.pl?p=patient/drugs/dru885.html&h=wbmdhd.txt&f=wbmdft.

txt (accessed 29 September 2005).

19 BioMarin Pharmaceutical Inc., Naglazyme Dosing andAdministration Guide, http://www.naglazyme.com/includes/

DoseAdminBroch.pdf (accessed 29 September 2005).

20 BioMarin Pharmaceutical Inc., “Clinical Support Materials,”

Naglazyme, http://www.naglazyme.com/csm.asp (accessed 29

September 2005).


Development,” op. cit.22 Genzyme Therapeutics, “Living with Fabry Disease,” Fabrazyme,

http://www.fabrazyme.com/patient/disease/fz_us_pt_ds_living.

asp (accessed 20 September 2005).

23 Genzyme Therapeutics, “Treatment,” Fabrazyme, http://www.

fabrazyme.com/patient/treat/fz_us_pt_tr_overview.asp (accessed

20 September 2005).

24 National Heart, Lung, and Blood Institute, What Is PulmonaryArterial Hypertension?, http://www.nhlbi.nih.gov/health/dci/

Diseases/pah/pah_what.html (accessed 12 September 2005).

25 Ibid.26 American Heart Association, Primary or Unexplained Pulmonary

Hypertension, http://www.americanheart.org/presenter.jhtml?

identifier=4752 (accessed 16 May 2005).


media, Inc., Flolan®, http://cp.gsm.com (accessed 16 May 2005).


media, Inc., Tracleer®, http://cp.gsm.com (accessed 16 May

2005).


media, Inc., Remodulin®, http://cp.gsm.com (accessed 16 May

2005).

30 Ibid.31 Food and Drug Administration, Patient Information Sheet:

Iloprost, http://www.fda.gov/cder/drug/InfoSheets/

patient/iloprostPIS.htm (accessed 12 September 2005).


media, Inc., Ventavis®, http://cp.gsm.com (accessed 16 May

2005).

33 National Library of Medicine, MedlinePlus Medical Encyclo-

pedia, Hypotension, http://www.nlm.nih.gov/medlineplus/

ency/article/003083.htm (accessed 12 September 2005).

Endnotes

27


Development (OOPD), Approved Orphan Drug Spreadsheet,

available upon request from OOPD.

35 National Library of Medicine, MedlinePlus Medical Encyclopedia,

Hypotension, op. cit.36 S. Reents et al., Clinical Pharmacology, Gold Standard Multi-

media, Inc., Midodrine, http://cp.gsm.com (accessed 3 August

2005).

37 Women and Pulmonary Hypertension, fact sheet, http://www.

phassociation.org/media/fact_women.pdf.

38 R. Stewart et al., “Pregnancy and Primary Pulmonary

Hypertension: Successful Outcome with Epoprostenol Therapy,”

Chest 119 (2001): 973–975.

39 Women and Pulmonary Hypertension, op. cit.40 Food and Drug Administration, “First Treatment for Crohn’s

Disease Approved” (24 August 1998), http://www.fda.gov/bbs/

topics/NEWS/NEW00651.html (accessed 13 September 2005).

41 National Institute of Diabetes and Digestive and Kidney

Diseases, Crohn’s Disease, http://digestive.niddk.nih.gov/

ddiseases/pubs/crohns/#caus (accessed 10 September 2005).

42 Food and Drug Administration, “First Treatment for Crohn’s

Disease Approved,” op. cit.43 S. R. Targan et al., “A Short-Term Study of Chimeric

Monoclonal Antibody cA2 to Tumor Necrosis Factor for

Crohn’s Disease,” The New England Journal of Medicine 337, no.

15 (1997): 1029–1036.



op. cit.45 National Institute of Diabetes and Digestive and Kidney

Diseases, National Kidney and Urological Diseases Information

Clearinghouse, Interstitial Cystitis, http://kidney.niddk.nih.gov/

kudiseases/pubs/interstitialcystitis (accessed 11 May 2005).

46 Interstitial Cystitis Network, Patient Handbook: About InterstitialCystitis (25 February 2005), http://www.ic-network.com/

handbook/basics.html (accessed 14 September 2005).

47 National Kidney and Urologic Diseases Information

Clearinghouse, “Interstitial Cystitis/Painful Bladder Syndrome,”

http://kidney.niddk.nih.gov/kudiseases/pubs/interstitialcystitis/

(accessed 20 January 2006).

48 Interstitial Cystitis Network, op. cit.49 S. Reents et al., Clinical Pharmacology, Gold Standard Multi-

media, Inc., Elmiron® (Pentosan), http://cp.gsm.com (accessed

11 May 2005).50 Interstitial Cystitis Network, Patient Handbook: About Oral

Medications (25 February 2005), http://www.ic-network.com/

handbook/oral.html (accessed 14 September 2005).

51 Ibid.52 Food and Drug Administration, Office of Orphan Products

Development, http://www.fda.gov/orphan.

53 Centocor, Inc., “John’s Story,” Remicade®, http://www.remicade.

com/crohns/your_crohns/crohns_johns_story.jsp (accessed 4

October 2005).

54 Food and Drug Administration, “FDA Approves First in a New

Class of Drugs to Treat Hyperparathyroidism Associated with

Renal Failure and in Patients with Parathyroid Cancer,” 8 March

2004, http://www.fda.gov/bbs/topics/ANSWERS/2004/

ANS01282.html (accessed 29 July 2005).



op. cit.56 S. Reents et al., Clinical Pharmacology, Gold Standard Multi-

media, Inc., Cinacalcet, http://cp.gsm.com (accessed 3 August

2005).

57 National Institute of Diabetes and Digestive and Kidney Diseases,

Acromegaly, http://www.niddk.nih.gov/health/endo/pubs/acro/

acro.htm (accessed 9 September 2005).

58 National Library of Medicine, MedlinePlus Drug Information,

Pegvisomant, http://www.nlm.nih.gov/medlineplus/druginfo/

uspdi/500469.html (accessed 9 September 2005).

59 Pfizer Inc., “What Is Somavert?” Somavert, http://www.somavert.

com/about/about.html (accessed 14 July 2005).

60 Food and Drug Administration, “FDA Approves First in a New

Class of Drugs to Treat Acromegaly,” (26 March 2003), http://

www.fda.gov/bbs/topics/NEWS/2003/NEW00885.html


61 University of Maryland Medical Center, “Endocrinology Health

Guide: Acromegaly,” University of Maryland Medical Center,http://www.umm.edu/endocrin/acromegaly.htm (accessed 18

August 2005).


Development,” op. cit.63 Andre R. Roussimoff Testamentary Trust, “Biography,” Andre

the Giant, http://www.andrethegiant.com/bio.html (accessed 4

October 2005).

64 eMedicine.com, Inc., “Acromegaly: Acromegaly Treatment,”

eMedicine Consumer Health, http://www.emedicinehealth.com/

articles/38312-6.asp (accessed 4 October 2005).

65 U.S. Department of Health and Human Services, Centers for

Disease Control and Prevention, http://www.cdc.gov/mmwr/

preview/mmwrhtml/ss4907a1.htm.

66 Centers for Disease Control and Prevention, What IsCryptosporidium?, http://www.cdc.gov/ncidod/dpd/parasites/

cryptosporidiosis/factsht_cryptosporidiosis.htm# (accessed 14

July 2005).

67 Centers for Disease Control and Prevention, http://www.cdc.gov/

ncidod/dpd/parasites/giardiasis/factsht_giardiasis.htm (accessed

14 July 2005)

68 National Organization for Rare Disorders, Giardiasis, http://www.

rarediseases.org/search/rdbdetail_abstract.html?disname=

Giardiasis (accessed 1 August 2005).

69 National Library of Medicine, MedlinePlus Drug Information,

Nitazoxanide, http://www.nlm.nih.gov/medlineplus/druginfo/

medmaster/a603017.html (accessed 14 July 2005).

70 Food and Drug Administration, “FDA Approves New Treatment

for Parasitic Infections in Pediatric Patients,” 2 December 2002,

http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01178.

html (accessed 3 October 2005).

28

71 Food and Drug Administration, “First Treatment Approved for

Rare Parasitic Infections,” 13 June 1996, http://www.fda.gov/bbs/

topics/ANSWERS/ANS00738.html (accessed 1 August 2005).

72 Centers for Disease Control and Prevention, Fact Sheet:Cysticercosis, http://www.cdc.gov/ncidod/dpd/parasites/

cysticercosis/factsht_cysticercosis.htm (accessed 3 October 2005).


Rare Parasitic Infections,” op. cit.74 National Library of Medicine, MedlinePlus Medical Encyclopedia,

Echinococcus, http://www.nlm.nih.gov/medlineplus/print/

ency/article/000676.htm (accessed 3 October 2005).


Rare Parasitic Infections,” op. cit.76 Ibid.77 National Library of Medicine, MedlinePlus Drug Information,

Albendazole (Systemic), http://www.nlm.nih.gov/medlineplus/

druginfo/uspdi/202668.html (accessed 3 October 2005).


Rare Parasitic Infections,” op. cit.79 Food and Drug Administration, “FDA Clears Tuberculosis Drug

for Marketing,” 23 June 1998, http://www.fda.gov/bbs/topics/

ANSWERS/ANS00880.html (accessed 15 September 2005).

80 American Lung Association, “Tuberculosis Fact Sheet,”

American Lung Association, http://www.lungusa.org/site/pp.asp?

c=dvLUK9O0E&b=35804 (accessed 15 September 2005).


media, Inc., Rifapentine, http://cp.gsm.com (accessed 3 August

2005).

82 Food and Drug Administration, “FDA Clears Tuberculosis Drug

for Marketing,” 23 June 1998, http://www.fda.gov/bbs/topics/

ANSWERS/ANS00880.html (accessed 15 September 2005).


Development, “List of All Approved Orphan Products Through

the Year 2005,”op. cit.84 M. Sarrel, “A History of Tuberculosis,” New Jersey Department of

Health and Senior Services, http://www.state.nj.us/health/cd/

tbhistry.htm (accessed 4 October 2005).

85 Merck & Co., Inc., “Thrombocytopenia,” The Merck ManualOnline Medical Library: Home Edition for Patients and Caregivers,http://www.merck.com/mmhe/sec14/ch173/ch173d.html

(accessed 14 July 2005).


media, Inc., Heparin®, http://cp.gsm.com (accessed 14 July

2005).

87 Berlex Laboratories, Inc., “Product Overview,” Refludan®,http://www.refludan.com/product/index.htm (accessed 15 July

2005).


Development (OOPD), Approved Orphan Spreadsheet, op. cit.89 National Heart, Lung, and Blood Institute, What Is Hemophilia?,

http://www.nhlbi.nih.gov/health/dci/Diseases/hemophilia/

hemophilia_what.html (accessed 14 July 2005).

90 Food and Drug Administration, “New Recombinant Product for

Hemophilia B,” 11 February 1997, http://www.fda.gov/bbs/topics/

ANSWERS/ANS00786.html (accessed 14 July 2005).


“Leprosy,” http://www.nlm.nih.gov/medlineplus/ency/

article/001347.htm (accessed 12 September 2005).

92 World Health Organization, Leprosy, http://www.who.int/

mediacentre/factsheets/fs101/en (accessed 12 September 2005).


“Leprosy,” op. cit.94 International Foundation of Anti-Leprosy Associations, “The

Management of Erythema Nodosum Leprosum,” ILEP TechnicalBulletin 9 (May 1996), http://www.ilep.org.uk/documents/

tb09eng.pdf (accessed 1 August 2005).

95 Food and Drug Administration, Thalidomid® ConsumerInformation, http://www.fda.gov/cder/news/thalinfo/thalomid.

htm (accessed 3 October 2005).

96 Food and Drug Administration, “FDA Approves Thalidomide

for Hansen’s Disease Side Effect, Imposes Unprecedented

Restrictions on Distribution,” 16 July 1998, http://www.fda.

gov/bbs/topics/ANSWERS/ANS00887.html (accessed 3

October 2005).


Development,” op. cit.98 “History of Leprosy,” Leprosy, http://www.stanford.edu/class/

humbio103/ParaSites2005/Leprosy/history.htm (accessed 4

October 2005).

99 American Lung Association, “Respiratory Distress Syndrome

of the Newborn Fact Sheet,” American Lung Association,http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35693



Respiratory Distress Syndrome in Infants, http://www.nlm.nih.

gov/medlineplus/ency/article/001563.htm (accessed 27

September 2005).

101 National Organization for Rare Disorders, Respiratory DistressSyndrome, Infants, full report, http://rarediseases.org/search/

rdb_fullreport_pf (accessed 29 July 2005).

102 Food and Drug Administration, Infasurf, 25 July 2000, http://

www.fda.gov/cder/consumerinfo/druginfo/infasurf.htm



media, Inc., Nitric Oxide, http://cp.gsm.com (accessed 3 August

2005).


media, Inc., Poractant Alfa, http://cp.gsm.com (accessed 3 August

2005).

105 Food and Drug Administration, “FDA Approves Drug to Treat

Rare Pediatric Liver Disease,” 22 January 2002, http://www.fda.

gov/bbs/topics/ANSWERS/2002/ANS01131.html (accessed 3

October 2005).

106 Ibid.

29

107 Tercica, Understanding Short Stature, http://investor.tercica.

com/releases.cfm (accessed 29 September 2005).

108 Drugs.com, “Increlex,” Drugs.com, http://www.drugs.com/

increlex.html (accessed 29 September 2005).

109 M. Herper, “FDA Approves Tercica’s Increlex,” Forbes.com,31 August 2005, http://www.forbes.com/markets/2005/08/

31/fda-increlex-tercica-0830markets01.html?partner=yahootix


110 Drugs.com, op. cit.111 Food and Drug Administration, “Office of Orphan Products

Development,” op. cit.112 C. Smith, “Lessons from a Boy Growing Old Before His Time,”

Seattle Post-Intelligencer, 16 September 2004, http://seattlepi.

nwsource.com/specials/seth/190908_progeriamain.asp

(accessed 4 October 2005).

113 M. Fox, “Cancer Drugs May Treat Aging Syndrome in Children,”

Reuters UK, 30 August 2005, http://today.reuters.co.uk/

news/newsArticle.aspx?type=healthNews&storyID=2005-08-

30T132533Z_ 01_MAR870933_RTRIDST_0_HEALTH-HEALTH-

AGING-DC.XML.

114 National Institute of Neurological Disorders and Stroke,

Narcolepsy, fact sheet, http://www.ninds.nih.gov/disorders/

narcolepsy/detail_narcolepsy.htm (accessed 24 August 2005).

115 National Organization for Rare Disorders, “Narcolepsy,” RareDisease Database, http://www.rarediseases.org/search/rdblist.

html (accessed 13 June, 2005).

116 National Library of Medicine, MedlinePlus Medical Encyclo-

pedia, Cataplexy, http://www.nlm.nih.gov/medlineplus/

print/ency/article/000802.htm (accessed 26 August 2005).

117 Food and Drug Administration, “FDA Approves Xyren for

Cataplexy Attacks in Patients with Narcolepsy,” 17 July 2002,

http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01157.

html (accessed 28 July 2005).


Narcolepsy Information Page, http://www.ninds.nih.gov/

disorders/narcolepsy/narcolepsy.htm (accessed 12 May 2005).

119 National Organization for Rare Disorders, “Narcolepsy,” op. cit.120 S. Reents et al., Clinical Pharmacology, Gold Standard Multi-

media, Inc., Provigil®, http://cp.gsm.com (accessed 12 May 2005).

121 HealthCommunities.com, SleepChannel, “Narcolepsy,”

http://www.sleepdisorderchannel.net/narcolepsy (accessed 12

May 2005).


Narcolepsy, op. cit.123 Food and Drug Administration, “FDA Approves Xyren for

Cataplexy Attacks in Patients with Narcolepsy,” op. cit.124 ALS Association, What Is ALS?, http://www.alsa.org/als/what.

cfm?CFID=1107473&CFTOKEN=16335905 (accessed 12

September 2005).

125 National Organization for Rare Disorders, “Amyotrophic

Lateral Sclerosis,” Rare Disease Database, http://www.rare

diseases.org/search/rdblist.html (accessed 2 June, 2005).

126 National Library of Medicine, MedlinePlus Medical

Encyclopedia, Amyotrophic Lateral Sclerosis, http://www.nlm.

nih.gov/medlineplus/ency/article/000688.htm (accessed 12

September 2005).

127 National Organization for Rare Disorders, “Amyotrophic Lateral

Sclerosis,” op. cit.128 Food and Drug Administration, “FDA Approves First Drug for

Lou Gehrig’s Disease,” press release, 12 December 1995,

http://www.fda.gov/bbs/topics/NEWS/NEW00522.html


129 Food and Drug Administration, “Glimmer of Hope for People

with ALS,” FDA Consumer Magazine (September 1996),

http://www.fda.gov/fdac/features/796_als.html (accessed 12

September 2005).

130 Ibid.131 National Organization for Rare Disorders, http://www.

rarediseases.org/info/about.html.

132 American Cancer Society, Inc., Cancer Facts and Figures 2005,http://www.cancer.org/downloads/STT/CAFF2005f4PWSecured.

pdf (accessed 8 September 2005).

133 Brain Tumor Society, Patient Resources: Common Brain Tumors,http://www.tbts.org/itemDetail.asp?categoryID=292&itemID

=16532 (accessed 15 July 2005).

134 S. Ubelacker, “New Drug Offers Hope to Brain Cancer Victims,”

Canadian Press (9 March 2005).

135 Brain Tumor Society, op. cit.136 S. Ubelacker, op. cit.137 Schering-Plough Corporation, “First New Chemotherapy Agent

for Brain Tumors in 20 Years,” press release, 11 August 1999,

http://virtualtrials.com/temodar%5Cpress.cfm (accessed

21 September 2005).

138 Pharmaceutical Research and Manufacturers of America, NewDrug Approvals in 1999 (Washington, DC: PhRMA, 2000).

139 R. Stupp et al., “Radiotherapy Plus Concomitant and Adjuvant

Temozolomide for Glioblastoma,” The New England Journal ofMedicine 352, no. 10 (10 March 2005): 987–986.

140 Pharmaceutical Research and Manufacturers of America,

Innovation.org, http://www.innovation.org/data/newsletter/

archives/?id=84 (accessed 3 October 2005).

141 American Cancer Society, Inc., “What Is Non-Hodgkin

Lymphoma?” American Cancer Society, http://www.cancer.org/

docroot/CRI/content/CRI_2_4_1X_What_Is_Non_Hodgkins_

Lymphoma_32.asp (accessed 3 October 2005).

142 Lymphoma Information Network, “Monoclonal Antibody

Therapy: Bexxar®,” Lymphoma Information Network: YourComprehensive Guide to Hodgkins and Non-Hodgkins Lymphoma,http://www.lymphomainfo.net/therapy/immunotherapy/

bexxar.html (accessed 3 October 2005).

143 Doctor’s Guide Publishing Limited, “FDA Approves Bexxar in

Patients with Follicular Non-Hodgkin’s Lymphoma,” Doctor’sGuide Personal Edition, http://www.docguide.com/news/content.

nsf/news/8525697700573E1885256D55004B52E3 (accessed 8

September 2005).

30

144 Lymphoma Information Network, op. cit. 145 National Cancer Institute, “Newly Approved Cancer Treatments:

Bexxar®,” National Cancer Institute, http://www.cancer.gov/

clinicaltrials/developments/newly-approved-treatments/page10

(accessed 21 November 2005).

146 Food and Drug Administration, “FDA Approves First Drug for

Rare Type of Cancer,” February 2004, http://www.fda.gov/bbs/

topics/NEWS/2004/NEW01018.html (accessed 29 August

2005).

147 Eli Lilly and Company, “Thoracic Cancer Patients Find New

Reasons for Hope with Alimta®,” press release, 3 July 2005,

http://newsroom.lilly.com/ReleaseDetail.cfm? ReleaseID=167952


148 National Cancer Institute, “Clinical Trial Results: Largest-Yet

Mesothelioma Study Shows Survival Benefit with New Drug,”

National Cancer Institute, May 2002, http://www.cancer.gov/

clinicaltrials/results/mesothelioma-study0502 (accessed 7

September 2005).

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Trisenox.HTM (accessed 27 September 2005).

155 “Definition of Acute promyelocytic leuemia, MedicineNet.com,

http://www.medterms.com/script/main/art.asp?articlekey

=19758.

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158 Pharmaceutical Research and Manufacturers of America,

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microsite/people_health/innovator_stories_mylotarg.htm


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Development,” op. cit.169 Ibid.170 Food and Drug Administration, “FDA Approves Arranon for

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31 October 2005, http://www.fda.gov/bbs/topics/NEWS/

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171 Food and Drug Administration, “FDA Approves First Oral Drug

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(accessed 10 February 2006).

172 Food and Drug Administration, “FDA Approved New Treatment

for Advanced Kidney Cancer,” 20 December 2005,

http://www.fda.gov/bbs/topics/NEWS/2005/NEW01282.html


173 Food and Drug Administration, “FDA Approves New Treatment

for Myelodysplastic Syndrome,” 28 December 2005,

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174 Adis R&D Insight Database, 15 February 2006.

31

175 T. Hampton, “Looking Beyond Imatinib: Next Line of Targeted

Drugs for CML Shows Promise,” The Journal of the AmericanMedical Association 295, no. 4 (2006): 369–370.

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177 Medical News Today, “Wyeth Initiates Clinical Trial with

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February 2005, http://www.medicalnewstoday.com/medicalnews.

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178 Muscular Dystrophy Campaign, “Myostatin Inhibitor (MYO-029)

Trial Announced By Wyeth,” 24 February 2005,

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179 Astellas US LLC, “Business Development: Immunology,”

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February 2006).

180 PR Newswire Europe Ltd., news release, “FK778, a novel com-

pound with multiple modes of action—a breakthrough in

transplant immunosuppression?,” 23 September 2003,

http://www.prnewswire.co.uk/cgi/news/release?id=108689


Much has been done…

...but the work continues.

The number of orphan drugs being

developed is going up: In 2004, there

were a record 160 applications for

orphan status, representing a 30 percent

increase over the average (124 per year)

of the prior four years.

Pharmaceutical Research and Manufacturers of America950 F Street, NW, Suite 300 • Washington, DC 20004

www.phrma.org

April 2006

advances in the treatment of rare...

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