new pipeline report 1stqtr final - walgreens · 2014. 5. 14. · pipeline report first quarter 2013...

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Pipeline Report

First quarter 2013

To help keep you informed about medications in development, the Walgreens pipeline report provides a summary of specialty medications that may be approved by the FDA within the next few years. While not all-inclusive, this report focuses on medications in phase III studies that may impact treatment for certain specialty disease states or conditions. It also highlights select, recently approved or soon-to-be-approved specialty medications of interest to the marketplace.

Medications to watch Here is a closer look at a few recently approved or soon-to-be-approved medications that may have a significant impact on therapeutic classes and treatment for specific disease states and conditions.

Iclusig (ponatinib) Iclusig was recently approved for the treatment of patients with chronic phase, accelerated phase or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to prior TKI therapy. Iclusig is an orally administered pan-BCR-ABL inhibitor that is active against native and mutant forms of BCR-ABL, including the T315I mutation.

Patients with chronic, accelerated or blast phase refractory CML or with Ph+ ALL that were resistant or intolerant to Sprycel (dasatinib) or Tasigna (nilotinib) or with the T315I mutation were enrolled in a single-arm phase II trial and received Iclusig 45 mg once daily. This trial is ongoing but results presented in June 2012 showed that 54 percent of chronic phase CML patients

in the trial achieved a major cytogenetic response. The most common adverse events in the trial were thrombocytopenia, rash, dry skin, abdominal pain and headache.

Iclusig is designated as an orphan drug. ARIAD Pharmaceuticals completed a rolling new drug application (NDA) submission in September 2012. The FDA granted priority review status to the application in October 2012. Iclusig was approved December 14, 2012, which was three months ahead of schedule.

Iclusig is also being evaluated in a phase III trial in patients with newly diagnosed CML. The efficacy of Iclusig will be compared to Gleevec (imatinib) based on evaluation of the primary endpoint of major molecular response rate at 12 months. ARIAD expects to complete patient enrollment in this trial by the end of 2013.

Dabrafenib and trametinib GlaxoSmithKline has developed dabrafenib and trametinib for the treatment of BRAF V600 mutation-positive melanoma. Approximately half of all metastatic melanoma patients are believed to have BRAF V600 mutations. Over 90 percent of these are V600E mutations, 5 to 6 percent are V600K mutations and the rest are V600R, V600E2 and V600D mutations.

Zelboraf (vemurafenib) is currently the only product approved for the treatment of BRAF V600E mutation-positive metastatic melanoma. Similar to Zelboraf, dabrafenib and trametinib are also orally administered and inhibit cell growth and survival. Dabrafenib is a BRAF kinase inhibitor and trametinib is a mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor.

Information on recently approved, soon to be approved and phase III trial specialty medications.

In a randomized, open-label, phase II trial, 250 patients with previously untreated, unresectable stage III or stage IV BRAF V600E mutation-positive metastatic melanoma were enrolled and randomized to receive treatment with dabrafenib 150 mg twice daily or dacarbazine 1000 mg/m2 intravenous (IV) infusion once every three weeks. The primary endpoint of the trial was progression-free survival (PFS). Median PFS was 5.1 months for dabrafenib and 2.7 months for dacarbazine. The most common adverse events in the dabrafenib group were skin-related toxicities, fever, fatigue, joint pain and headache.

In a separate phase III trial, 322 patients with BRAF V600E/K mutation-positive metastatic melanoma were enrolled and randomized to receive trametinib 2 mg daily or chemotherapy (with dacarbazine IV infusion or paclitaxel IV infusion). The primary endpoint of the trial was also PFS. Median PFS was 4.8 months for trametinib and 1.4 months for chemotherapy. The most common adverse events in the trametinib group were skin rash, diarrhea, edema, hypertension and fatigue.

GlaxoSmithKline filed an NDA for dabrafenib in July 2012 and for trametinib in August 2012. Responses to the NDA are expected in May 2013 and June 2013, respectively. Both agents are designated as orphan drugs.

Apremilast Apremilast is an investigational medication for the treatment of psoriatic arthritis (PsA). There are four biologic disease-modifying antirheumatic drugs (DMARDs) approved for the treatment of PsA including Enbrel (etanercept), Humira (adalimumab), Simponi (golimumab) and Remicade (infliximab). Apremilast is an oral phosphodiesterase type 4 (PDE4) inhibitor that modulates the inflammatory response.

Apremilast has been evaluated in three phase III, double-blind, placebo-controlled trials. Patients with PsA who had received or failed oral DMARDs and/or biologic DMARDs were enrolled in these trials. In the PALACE-1 trial, patients were randomized to apremilast alone or in combination with oral DMARDs. The primary endpoint of the study was the proportion of patients who achieved the American College of Rheumatology criteria for a 20 percent improvement (ACR20), compared with baseline after 16 weeks of treatment. Statistically significant higher ACR20 responses were found in the apremilast 20 mg or 30 mg twice daily monotherapy groups (31.5 percent and 50.8 percent, respectively) compared with the placebo group (10.5 percent). No meaningful advantage was observed in adding oral DMARDs to apremilast. The primary endpoint of ACR20 at week 16 was also achieved for patients receiving apremilast 20 mg and 30 mg twice daily in the PALACE-2 and PALACE-3 trials.

Apremilast is also in phase III trials for the treatment of psoriasis and ankylosing spondylitis. Celgene plans to file an NDA for apremilast in the treatment of PsA in the first half of 2013.

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Medications recently approved Manufacturer/ Drug name

Indication Mechanism of action/Drug class

Route of administration

Approval date

Comments

Inflammatory diseases Abbott/Humira (adalimumab)

For inducing and sustaining clinical remission in patients with moderately to severely active ulcerative colitis who have had an inadequate response to immuno-suppressants, such as corticosteroids, azathioprine or 6-mercaptopurine

Targets tumor necrosis factor (TNF) alpha, which is involved in the inflammatory process/TNF inhibitor

Subcutaneous (SC) injection

9/28/2012 • Previously approved for the treatment of rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis, PsA, ankylosing spondylitis, Crohn’s disease and plaque psoriasis

Pfizer/Xeljanz (tofacitinib)

For the treatment of adult patients with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate

Interferes with the inflammatory and immune responses/ Janus kinase (JAK) inhibitor

Oral 11/6/2012 • First JAK inhibitor approved for the treatment of RA

Neuroendocrine disorders Novartis/Signifor (pasireotide diaspartate)

For the treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative

Binds somatostatin receptors/ Somatostatin analogue

SC injection 12/14/2012 • Also in phase III trials for the treatment of acromegaly

Oncology ARIAD Pharmaceuticals/ Iclusig (ponatinib)

For the treatment of adult patients with chronic phase, accelerated phase or blast phase CML or Ph+ ALL that is resistant or intolerant to prior TKI therapy

Inhibits native and mutant forms of BCR-ABL/ Pan-BCR-ABL inhibitor

Oral 12/14/2012 • Walgreens Specialty Pharmacy is a distributor of this medication

Bayer HealthCare/ Stivarga (regorafenib)

For the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with currently available therapies, including: fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an antivascular endothelial growth factor (anti-VEGF) therapy, and, if KRAS wild-type, an anti-epidermal growth factor receptor (anti-EGFR) therapy

Reduces tumor cell growth and blood supply/Multikinase inhibitor

Oral 9/27/2012 • Walgreens Specialty Pharmacy is a distributor of this medication

Medications recently approved (continued)

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Manufacturer/ Drug name



Approval date

Comments

Oncology Celgene/Abraxane (paclitaxel protein-bound particles)

For the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy

Promotes assembly and stabilizes microtubules, resulting in inhibition of cellular division/ Microtubule inhibitor

IV infusion 10/12/2012 • Previously approved for the treatment of breast cancer

Exelixis/Cometriq (cabozantinib)

For the treatment of progressive, metastatic medullary thyroid cancer (MTC)

Inhibits cell growth and survival/TKI

Oral 11/29/2012 • Second medication approved to treat MTC in the past two years

Johnson & Johnson/ Zytiga (abiraterone acetate)

In combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC)

Suppresses testosterone production/ Androgen biosynthesis inhibitor

Oral 12/10/2012 • Previously approved to treat metastatic CRPC in patients who had received prior chemotherapy containing docetaxel

Teva Pharmaceuticals/ Synribo (omacetaxine mepesuccinate)

For the treatment of patients with chronic or accelerated phase CML with resistance and/or intolerance to two or more TKIs

Inhibits protein translation of oncoproteins/ Cetaxine

SC injection 10/26/2012 • Administered by a healthcare professional

Ophthalmology Regeneron Pharmaceuticals/ Eylea (aflibercept)

For the treatment of macular edema following central retinal vein occlusion

Binds VEGF and placental growth factor/Antiangio-genesis inhibitor

Intravitreal injection

9/21/2012 • Previously approved for the treatment of neovascular age-related macular degeneration (AMD)

ThromboGenics/ Jetrea (ocriplasmin)

For the treatment of symptomatic vitreomacular adhesion

Targets the fibronectin, laminin and type IV collagen fibers that adhere the vitreous to the retina/ Proteolytic enzyme

Intravitreal injection

10/18/2012 • First medication approved for this indication

Osteoporosis Amgen/Prolia (denosumab)

For the treatment to increase bone mass in men with osteoporosis at high risk for fracture

Inhibits bone destruction/ Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor

SC injection 9/20/2012 • Previously approved for the treatment of postmenopausal osteoporosis and cancer, induced bone loss

Thrombocytopenia GlaxoSmithKline/ Promacta (eltrombopag)

For the treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy

Stimulates platelet production/ Thrombopoietin receptor agonist

Oral 11/19/2012 • Previously approved for the treatment of chronic immune thrombocytopenia

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Pipeline medications in phase III trials Manufacturer/ Drug name



Comments

Bleeding disorders Baxter/BAX 326 (recombinant factor IX)

For the treatment and prevention of bleeding in patients with hemophilia B

Replaces deficient factor/Factor replacement therapy

IV infusion • Biologics license application (BLA) filed September 2012

Biogen Idec/ Recombinant factor VIII Fc fusion protein

For the treatment and prevention of bleeding in patients with hemophilia A


IV infusion • BLA filing planned for the first half of 2013

Biogen Idec/ Recombinant factor IX Fc fusion protein



IV infusion • BLA filing planned for the first half of 2013

Inspiration Biopharmaceuticals/ IXinity (trenonacog alfa, IB1001)



IV infusion • BLA filed April 2012

Inspiration Biopharmaceuticals/ OBI-1 (recombinant porcine factor VIII)

For the treatment of hemophilia A in patients with inhibitory antibodies


IV infusion • FDA granted fast-track status • BLA filing planned for the first

half of 2013

Novo Nordisk/ Turoctocog alfa (NN7008)

For the treatment and prevention of bleeding in patients with hemophilia A


IV infusion • BLA filed October 2012

Chronic fatigue syndrome Hemispherx Biopharma/ Ampligen (rintatolimod)

For the treatment of chronic fatigue syndrome

Stimulates the immune system/Toll-like receptor 3 agonist

IV infusion • Designated as an orphan drug • NDA accepted for review

July 2008 • Received a complete

response letter November 2009

• NDA resubmitted July 2012 • A response to the NDA is

expected February 2013 Familial lipid disorders

Aegerion Pharmaceuticals/ Lomitapide

For the treatment of homozygous familial hypercholesterolemia (HoFH)

Interferes with the production of lipoproteins/Microsomal triglyceride transfer protein inhibitor (MTP-I)

Oral • Designated as an orphan drug

• NDA filed February 2012 • A response to the NDA is

expected December 2012 Genzyme and Isis Pharmaceuticals/ Kynamro (mipomersen)

For the treatment of HoFH

Prevents the production of apolipoprotein B/ Apolipoprotein B synthesis inhibitor

SC injection • Designated as an orphan drug

• NDA filed March 2012 • A response to the NDA is

expected January 2013 Fertility

Merck/ Corifollitropin alfa

For the development of multiple follicles and pregnancy in women participating in an assisted reproductive technology program

Stimulates ovarian follicular growth/ Sustained follicle stimulant

SC injection • Primary endpoint achieved in phase III trial October 2012

• NDA filing anticipated in 2013

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Pipeline medications in phase III trials (continued)




Comments

Hepatitis Gilead Sciences/ Sofosbuvir

In combination with ribavirin for the treatment of patients with genotype 2 or 3 chronic hepatitis C virus (HCV) infection who are not candidates for interferon

Prevents virus replication/Nucleotide analogue polymerase inhibitor

Oral • Positive phase III results reported November 2012

• Two other phase III trials ongoing

• First regulatory submission expected in mid-2013

Tibotec Pharmaceuticals/ Simeprevir (TMC435)

In combination with peginterferon alfa and ribavirin for the treatment of chronic HCV infection in treatment-naive and treatment-failure patients

Prevents virus replication/NS3/4A protease inhibitor

Oral • FDA granted fast-track status • Phase III trials ongoing • NDA filing anticipated in the

first half of 2013

Hereditary angioedema Pharming Group NV and Santarus/ Ruconest (C1 inhibitor)

For the treatment of acute attacks in patients with hereditary angioedema

Replaces deficient C1 inhibitor/C1 inhibitor replacement therapy

IV infusion • Designated as an orphan drug

• Primary endpoint achieved in phase III trial November 2012

• BLA filing is expected in the first half of 2013

Human immunodeficiency virus Gilead Sciences/ Cobicistat

To increase blood levels of certain protease inhibitors to enable once-daily dosing

Inhibits cytochrome P4503A/ Pharmacoenhancer

Oral • NDA filed June 2012 • A response to the NDA is

expected April 2013

Gilead Sciences/ Elvitegravir

For the treatment of human immunodeficiency virus (HIV) in treatment-experienced patients

Prevents virus replication/Integrase inhibitor

Oral • NDA filed June 2012 • A response to the NDA is

expected April 2013

ViiV Healthcare/ Dolutegravir

In combination with other antiretrovirals for the treatment of HIV

Prevents virus replication/Integrase inhibitor

Oral • NDA filed December 2012

Inflammatory diseases AstraZeneca/ Fostamatinib

For the treatment of RA

Blocks signaling in multiple cell types involved in inflammation and tissue degradation/ Spleen tyrosine kinase inhibitor

Oral • First set of data from phase III trials expected in the first half of 2013

• NDA filing planned for the second half of 2013

Celgene/Apremilast For the treatment of PsA Modulates the inflammatory response/PDE4 inhibitor

Oral • NDA filing is expected in the first half of 2013

Novartis/ Secukinumab (AIN457)

For the treatment of plaque psoriasis

Interferes with the inflammatory response/ Interleukin-17A (IL-17A) inhibitor

SC injection • Results from phase III trial expected in 2013, with regulatory submissions to follow shortly thereafter

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Pipeline medications in phase III trials (continued) Manufacturer/ Drug name



Comments

Lysosomal storage diseases Amicus Therapeutics and GlaxoSmithKline/ Amigal (migalastat HCI)

For the treatment of Fabry disease

Binds to and stabilizes alpha-galactosidase/ Alpha-galactosidase A enhancer

Oral • Designated as an orphan drug

• Completed enrollment in second phase III trial October 2012

• Results from the first phase III trial are expected in the fourth quarter of 2012

BioMarin Pharmaceuticals/ GALNS

For the treatment of mucopolysaccharidosis type IVA (Morquio A syndrome)

Replaces deficient N-acetylgalactosamine-6 sulfatase/Enzyme replacement therapy

IV infusion • First regulatory submission is expected in the first quarter of 2013

Genzyme/ Eliglustat

For the treatment of Gaucher disease

Reduces the production of glucocerebroside/ Glucosylceramide synthase inhibitor

Oral • Designated as an orphan drug • Primary endpoint met in first

phase III trial October 2012 • Results from second

phase III trial are expected in early 2013

Multiple sclerosis Biogen Idec/ BG-12 (dimethyl fumarate)

For the treatment of relapsing-remitting multiple sclerosis (MS)

Activates the Nrf2 transcriptional pathway, which regulates the antioxidant response/ Gene transcription modulator

Oral • NDA filed February 2012 • A response to the NDA was

expected December 2012; however, the FDA has extended the review period

• A response is now expected March 2013

Teva Pharmaceuticals/ Laquinimod

For the treatment of relapsing-remitting MS

Inhibits autoimmune and inflammatory disease activity/ Immunomodulatory agent

Oral • Teva to initiate a third phase III trial following an agreement with the FDA on the special protocol assessment (SPA)

Neurogenic disorders Chelsea Therapeutics/ Northera (droxidopa)

For the treatment of symptomatic neurogenic orthostatic hypotension in patients with primary autonomic failure, dopamine beta-hydroxylase deficiency and nondiabetic autonomic neuropathy

Increases norepinephrine levels in the nervous system/Synthetic catecholamine

Oral • Designated as an orphan drug with fast-track status

• NDA filed September 2011 • Received a complete

response letter March 2012 • FDA recommended an

additional clinical trial

Neutropenia Teva Pharmaceuticals/ Lipegfilgrastim

To reduce the duration of severe neutropenia in cancer patients undergoing chemotherapy

Long-acting granulocyte colony-stimulating factor

SC injection • Primary endpoint achieved in phase III trial June 2011

• BLA filing anticipated in 2012

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Pipeline medications in phase III trials (continued) Manufacturer/ Drug name



Comments

Oncology AVEO Oncology and Astellas/ Tivozanib

For the treatment of advanced renal cell carcinoma (RCC)

Reduces tumor cell growth and blood supply/VEGF receptor inhibitor

Oral • NDA filed September 2012 • A response to the NDA is

expected July 2013

Bayer HealthCare/ Alpharadin (radium-223 chloride)

For the treatment of patients with CRPC and bone metastases

Mimics the behavior of calcium in the bone to target areas of high bone turnover in and around bone metastases/ Alpha-pharmaceutical

IV infusion • FDA granted fast-track status • Primary endpoint achieved in

phase III trial June 2011 • First regulatory submission

planned for the second half of 2012

Celgene Corporation/ Pomalidomide

For the treatment of relapsed/refractory multiple myeloma (MM) and myelofibrosis

Possesses immunomodulatory, anti-inflammatory and antiangiogenic properties/Thalidomide analogue

Oral • Data from phase III trial in myelofibrosis expected by the end of 2012

• NDA filed for MM in the first quarter of 2012

• A response to the NDA is expected February 2013

Cell Therapeutics/ Opaxio (paclitaxel poliglumex)

For the treatment of ovarian cancer

Promotes assembly and stabilizes microtubules, resulting in inhibition of cellular division/Microtubule inhibitor

IV infusion • Links paclitaxel to a biodegradable polyglutamate polymer that delivers more chemotherapy to tumor cells

• Interim analysis of phase III trial may be available in 2013

Eisai/Lenvatinib For the treatment of thyroid cancer


Oral • NDA filing planned for 2013

GlaxoSmithKline/ Dabrafenib

For the treatment of BRAF V600 positive melanoma

Inhibits cell growth and survival/BRAF kinase inhibitor

Oral • Designated as an orphan drug • NDA filed July 2012 • A response to the NDA is

expected May 2013 GlaxoSmithKline/ Trametinib

For the treatment of BRAF V600 positive melanoma

Inhibits cell growth and survival/MEK inhibitor

Oral • Designated as an orphan drug • NDA filed August 2012 • A response to the NDA is

expected June 2013 Novartis/ Dovitinib

For the treatment of RCC Inhibits cell growth and survival/Fibroblast growth factor receptor inhibitor


Onconova Therapeutics/ Rigosertib

For the treatment of refractory myelodysplastic syndromes

Targets alpha and beta isoforms of PI-3 kinases/Multikinase inhibitor

IV infusion • An oral formulation is also in development

• NDA filing planned for 2013

Spectrum Pharmaceuticals/ Belinostat

For the treatment of relapsed or refractory peripheral T-cell lymphoma

Inhibits cell growth and survival/Histone deacetylase inhibitor

IV infusion • Designated as an orphan drug • NDA filing planned for

mid-2013

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Pipeline medications in phase III trials (continued)




Comments

Primary immunodeficiency Biotest/Bivigam Replacement therapy for

primary immunodeficiency

Replaces deficient immunoglobulin/ Replacement therapy

IV infusion • BLA filed November 2010 • A response to the BLA was

expected in the third quarter of 2012

• FDA requested more information August 2012

• Additional data submitted to the FDA October 2012

Pulmonary arterial hypertension Actelion/Opsumit (macitentan)

For the treatment of pulmonary arterial hypertension (PAH)

Reduces vascular smooth muscle constriction/ Endothelin receptor antagonist

Oral • Designated as an orphan drug • NDA filed October 2012

Bayer HealthCare/ Riociguat

For the treatment of PAH Reduces vascular smooth muscle constriction/Soluble guanylate cyclase stimulator

Oral • First regulatory submission planned for the first half of 2013

Short bowel syndrome NPS Pharmaceuticals/ Gattex (teduglutide)

For the treatment of short bowel syndrome by reducing patients' dependence on IV feeding

Promotes gastrointestinal regeneration/Analogue of glucagon-like peptide-2


• Rolling BLA completed December 2011

• A response to the BLA was expected September 2012; however, the FDA has extended the review period

• A response is now expected December 2012

Thrombocytopenia Eisai/ Avatrombopag

For the treatment of chronic immune thrombocytopenia

Stimulates platelet production/ Thrombopoietin receptor agonist


New dosage forms in the pipeline Manufacturer/ Drug name


Current route of administration

Investigational route of administration*

Comments

Cystic fibrosis Novartis/TOBI Podhaler (tobramycin)

For the treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients

Disrupts protein synthesis/ Aminoglycoside antibiotic

Solution for inhalation

Powder for inhalation

• NDA filed December 2011

• A response to the NDA is expected October 2012

• Received a complete response letter October 2012; the FDA identified deficiencies in a third-party manufacturing facility and did not request additional clinical data

*Dosage form is not available. Only investigational route of administration is available at this time.

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*Dosage form is not available. Only investigational rate of administration is available at this time.

New dosage forms in the pipeline (continued)



Current route of administration

Investigational route of administration*

Comments

Cystic fibrosis Pharmaxis/ Bronchitol (mannitol)

For the treatment of CF

Hydrates the lungs/Osmotic diuretic

IV infusion, inhalation

Inhalation • Designated as an orphan drug

• NDA filed May 2012 • A response to the NDA is

expected March 2013 Inflammatory diseases

Janssen/Simponi (golimumab)


Targets TNF alpha, which is involved in the inflammatory process/TNF inhibitor

SC injection IV infusion • BLA filed September 2012

Lysosomal storage diseases Raptor Pharmaceuticals/ Procysbi (cysteamine bitartrate delayed-release)

For the treatment of nephropathic cystinosis

Reduces cystine levels in cells/ Aminothiol

Oral Oral • Formulated to be sprinkled onto food for administration

• Designated as an orphan drug

• NDA filed March 2012 • A response to the NDA is

expected January 2013 Multiple sclerosis

Biogen Idec and Abbott/ Daclizumab HYP (high-yield process)


Binds to the CD25 receptor on T cells/Therapeutic antibody

IV infusion SC injection • Phase III results expected in 2014

• Marketed as Zenapax for the prevention of acute kidney rejection

Teva Pharmaceutical/ Copaxone (glatiramer acetate)


Modulates the immune system/ Disease modifying therapy

SC injection SC injection • Higher dose formulation administered three times a week instead of daily

• NDA filing is expected in the first quarter of 2013

Oncology Genentech/ Trastuzumab emtansine (T-DM1)

For the treatment of HER2-positive metastatic breast cancer

Inhibits the proliferation of tumor cells that overexpress HER2/Antibody-drug conjugate

IV infusion IV infusion • Links trastuzumab antibody to anticancer agent

• BLA filed August 2012 • FDA granted priority

review status • A response to the BLA is

expected February 2013 Roche/Herceptin (trastuzumab)

For the treatment of HER2-positive early breast cancer

Inhibits the proliferation of tumor cells that overexpress HER2/Monoclonal antibody

IV infusion SC injection • Coprimary endpoints achieved in phase III trial October 2011

• Two additional studies are currently ongoing

Pulmonary arterial hypertension United Therapeutics/ Treprostinil diethanolamine

For the treatment of PAH

Dilates pulmonary blood vessels/ Prostacyclin analogue

Continuous SC or IV infusion and inhalation

Oral • NDA filing accepted February 2012

• Received a complete response letter October 2012

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New indications in the pipeline Manufacturer/ Drug name

Current indication

Investigational indication

Mechanism of action/Drug class


Comments

Inflammatory diseases Genentech/ Actemra (tocilizumab)

For the treatment of RA and systemic juvenile idiopathic arthritis (SJIA)

For the treatment of polyarticular juvenile idiopathic arthritis

Blocks IL-6 receptors/ Monoclonal antibody

IV infusion • sBLA filed June 2012 • A response to the sBLA

is expected April 2013

Janssen/Simponi (golimumab)

For the treatment of RA, PsA and ankylosing spondylitis

For the treatment of ulcerative colitis

Targets TNF-alpha, which is involved in the inflammatory process/TNF inhibitor

SC injection • sBLA filed July 2012 • A response to the sBLA

is expected May 2013

Novartis/Ilaris (canakinumab)

For the treatment of cryopyrin-associated periodic syndromes (CAPS)

For the treatment of SJIA

Targets IL-1 beta/IL-1 beta inhibitor

SC injection • sBLA filing planned for the fourth quarter of 2012

Regeneron Pharmaceuticals/ Arcalyst (rilonacept)

For the treatment of CAPS, including familial cold auto-inflammatory syndrome and Muckle-Wells syndrome

For the prevention of gout flares in patients initiating uric acid-lowering therapy

Binds and neutralizes IL-1/ Long-acting IL-1 inhibitor

SC injection • sBLA filed September 2011

• Received a complete response letter July 2012

• Development for gout has been discontinued

Swedish Orphan Biovitrum (Sobi)/ Kineret (anakinra)


For the treatment of neonatal-onset multisystem inflammatory disease

Inhibits IL-1 binding to the IL-1 type I receptor/ IL-1 receptor antagonist


• sBLA filed June 2012 • FDA granted priority

review status • A response to the

sBLA is expected December 2012

UCB Pharma/ Cimzia (certolizumab pegol)

For the treatment of Crohn’s disease and RA

For the treatment of PsA

Targets TNF alpha, which is involved in the inflammatory process/TNF inhibitor

SC injection • sBLA filing anticipated by the end of 2012

Multiple sclerosis Genzyme/ Lemtrada (alemtuzumab)

For the treatment of B-cell chronic lymphocytic leukemia (CLL)

For the treatment of relapsing MS

Binds to the CD52 antigen on B cells and T cells/ Therapeutic antibody

IV infusion • FDA granted fast-track status

• sBLA filed June 2012 • Received a refuse to file

letter from the FDA August 2012

• Refiling is on track • Marketed as Campath

for CLL indication Neuroendocrine disorders

Novartis Signifor (pasireotide diaspartate)

For the treatment of Cushing’s disease

For the treatment of acromegaly

Binds somatostatin receptors/ Somatostatin analogue


• Primary endpoint achieved in phase III acromegaly trial May 2012

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New indications in the pipeline (continued)


Current indication




Comments

Oncology Astellas/Tarceva (erlotinib)

For the treatment of NSCLC after failure of at least one prior chemo-therapy regimen, for maintenance treatment of NSCLC and for the treatment of pancreatic cancer

For the first-line treatment of EGFR-mutation-positive NSCLC

Reduces tumor cell growth and blood supply/ TKI

Oral • sNDA filed November 2012

Bayer HealthCare/ Stivarga (regorafenib)

For the treatment of metastatic CRC

For the treatment of metastatic and/or unresectable gastrointestinal stromal tumors (GIST)

Reduces tumor cell growth and blood supply/ Multikinase inhibitor

Oral • Designated as an orphan drug with fast-track status

• NDA filed August 2012 • FDA granted priority

review status • A response to the

NDA is expected February 2013

Novartis/Tasigna (nilotinib)

For the treatment of chronic and accelerated phase Ph+ CML in patients resistant or intolerant to prior therapy that included Gleevec, and for the first-line treatment of Ph+ CML

For the treatment of c-Kit-positive melanoma


Oral • sNDA planned for 2014

Peyronie’s disease Auxilium Pharmaceuticals/ Xiaflex (collagenase clostridium histolyticum)

For the treatment of Dupuytren’s contracture with a palpable cord

For the treatment of Peyronie’s disease

Breaks down collagen deposits/ Purified collagenase

Injection • Designated as an orphan drug

• sBLA filed November 2012

• Requested a priority review

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New indications in the pipeline (continued)


Current indication




Comments

Pulmonary arterial hypertension Novartis/ Gleevec (imatinib)

For the treatment of CML, ALL, myelodysplastic/ myelo-proliferative diseases, aggressive systemic mastocytosis, hypereosinophilic syndrome, chronic eosinophilic leukemia, dermato-fibrosarcoma protuberans and GIST

For the treatment of PAH

Improves pulmonary vascular resistance and increases cardiac output/TKI

Oral • sNDA filed in February 2012

• Filing withdrawn in the third quarter of 2012

Transplant Novartis/Zortress (everolimus)

For the prevention of organ rejection in patients receiving a kidney transplant

For the prevention of organ rejection in patients receiving a liver transplant

Inhibits proliferation of T-cells/ Mammalian target of rapamycin inhibitor

Oral • sNDA filed in the fourth quarter of 2011

• A response to the sNDA is expected in the fourth quarter of 2012

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Glossary of terms Accelerated approval – allows pharmaceutical companies to obtain approval for products based on less clinical data than typically required for a normal approval, and is used for patients considered to have unmet medical needs.

BLA – stands for “biologics license application,” similar to an NDA, but used for investigational medications that are considered to be biologic agents.

Complete response letter – issued to let the applicant know that the review period for an investigational agent is complete and that the NDA or BLA is not yet ready for approval.

Cystic fibrosis – CF.

Double-blind trial – a type of study in which the participants and the investigators are blinded to treatment; this type of study has less bias than nonblinded studies.

Expanded access program – manufacturer programs that allow the distribution of new medications prior to FDA approval for patients with a life-threatening condition who cannot be treated successfully with currently available medications.

Fast track – designation granted by the FDA to an investigational agent indicating an expedited review of the NDA or BLA; usually applies to medications that treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs.

Hereditary angioedema – HAE.

Multiple sclerosis – MS.

NDA – stands for “new drug application,” the process by which a manufacturer submits information to the FDA to gain approval for the agent; conducted after phase III development is completed.

Orphan drug – a medication that treats a rare disease that affects fewer than 200,000 Americans. A medication granted orphan drug status is entitled to seven years of marketing exclusivity.

Phase II – second phase of medication development; typically involves several hundred patients to determine safety and preliminary data on efficacy.

Phase III – last phase of medication development; involves safety and efficacy trials of the new medication. This phase of development can take years to complete.

Priority review – designation granted by the FDA to an investigational agent after it has been submitted to the FDA for approval; a priority designation means that the FDA will review and take action on the application (approve or not approve) within six months instead of the standard 10 months for all other medication filings.

Pulmonary arterial hypertension – PAH.

Randomized controlled trial – a study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. It is the most powerful study design in clinical research.

Refusal to file letter – a letter the FDA issues to the applicant if it determines the application is not sufficiently complete.

Rheumatoid arthritis – RA.

Risk evaluation and mitigation strategy (REMS) – a strategy to manage a known or potential serious risk associated with a drug or biological product. This strategy will be required if the FDA finds that a REMS is necessary to ensure that the benefits of the drug or biological product outweigh its risks.

Rolling submission – usually applies to fast-track medications; indicates that the review process can be started even before the FDA receives all the information. However, the FDA requires all the information before a final decision about approval can be made.

sBLA – stands for “supplemental biologics license application,” similar to sNDA but used for already approved investigational medications that are considered to be biologic agents.

sNDA – stands for “supplemental new drug application,” the process by which a pharmaceutical company submits information to the FDA to gain approval for a new indication for an agent that has already been approved by the FDA.

SPA – stands for “special protocol assessment,” an agreement with the FDA that the manufacturer’s clinical protocol for a phase III trial is acceptable to support an NDA or BLA.

Treatment-naive – patients who have never been treated before for a particular condition.

15

References Journals: Ascierto PA, Kirkwood JM, Grob JJ, et al. The role of BRAF V600 mutation in melanoma. J Transl Med. 2012;10:85.

Cortes JE, Kim DW, Pinilla-Ibarz J, et al. PACE: a pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. J Clin Oncol. 2012;30(suppl):abstract 6503.

Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380:358-365.

Hauschild A, Grob JJ, Demidov LV, et al. Phase III, randomized, open-label, multicenter trial (BREAK-3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAF V600E mutated melanoma. J Clin Oncol. 2012;30(suppl):abstract LBA8500.

Robert C, Flaherty KT, Hersey P, et al. METRIC phase III study: efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAF V600E/K mutant advanced or metastatic melanoma (MM). J Clin Oncol. 2012;30(suppl):abstract LBA8509.

Schett G, Wollenhaupt J, Papp K, et al. Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012;64(10):3156-3167.

Websites: Adis Insight - http://bi.adisinsight.com

ClinicalTrials.gov - www.clinicaltrials.gov

Manufacturers’ websites

U.S. Food and Drug Administration - www.fda.gov

Information in the report is current as of December 2012, and was accessed on December 17, 2012. This report is for educational purposes only and is not deemed as an endorsement by Walgreen Co., its subsidiaries or affiliates. Claims made in this report about the efficacy of medications or the results of studies have been made by the medication manufacturer, the FDA or another third party.

Editorial Board - Editor Stacy Goldman Author Amy Pfeifer, PharmD Project Lead Tim Kosmaczewski Designer Edmond He

©2013 Walgreen Co. All rights reserved. 12SP0111-0113

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