pinksheet...pricing prescription drugs, and how access might be affected, under a single-payer...

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SheetPinkpink.pharmaintelligence.informa.com Vol. 81 / No. 18 May 6, 2019

F R O M T H E E D I TO R S O F S C R I P R E G U L ATO RY A F FA I R S , T H E R P M R E P O RT , G O L D S H E E T , P I N K S H E E T DA I LY A N D P I N K S H E E T

REGULATORY UPDATE

Real-World Evidence: Observational Studies Deserve More Respect In US FDA Framework, p. 8

REIMBURSEMENT

Medicare Part D Spending in 2019 Lower Than Expected Because Of Rebates, p. 14

NEW PRODUCTS

ViiV’s Potential HIV Blockbuster Among Latest Drugs To Win EMA Nod, p. 11

CONTINUED ON PAGE 4

UK Plan To Speed Access To ‘Cutting-Edge’ ProductsIAN SCHOFIELD [email protected]

T he UK government says that cutting-edge medicines, diag-nostic tools and digital services will be made available on the national health service (NHS) more quickly as a result of improvements to the Accelerated Access Collaborative.

The AAC, which was set up in 2018 to speed up access to ground-breaking products for conditions like cancer, dementia and diabetes, is to become the new “umbrella organization for UK health innovation.”

It will act as the “front door” for innovative companies seeking to have their products funded by the NHS, and will “provide support to overcome barriers that can prevent the best medical innova-tions from reaching patients,” the government said. A new unit will be established in NHS England and NHS Improvement, led by Sam Roberts, NHS England’s director of innovation, as chief executive.

The revamped AAC was announced on 2 May by health minister Nicola Blackwood, who said: “I want the NHS to be at the forefront of cutting-edge treatments and medical innovations – but often it can take too long for products to get from the bench to the bedside.”

She said the AAC would now be able to speed up this process “so patients and the NHS can be the first in the world to benefit from the most transformative technologies and treatments as part of our Long Term Plan.”

In its new incarnation, the AAC is intended to implement a sys-tem that can identify the best new innovations, “make sure the NHS is ready to make use of them,” and help the service adopt clinically and cost-effective innovations more quickly, the government said.

It will also set up a “globally leading testing infrastructure” that allows innovators to “generate the evidence they need to get their products into the NHS.”

These moves will complement efforts that have already been made to bring the NHS into the “horizon scanning” system and ensure that it is prepared for highly innovative products coming down the pipeline so that they can be made available to patients as quickly as possible, as part of the new voluntary pricing and ac-cess scheme that took effect at the beginning of this year. (Also see

“ABPI Exec Lauds Innovation And Access Provisions In New UK Volun-tary Scheme” - Pink Sheet, 29 Apr, 2019.)

Other objectives of the revamped AAC are:

• To provide a single point of call for innovators working inside or outside the NHS, so that they can “understand the system and where to go for support.”

• To signal the needs of clinicians and patients “so innovators know which problems they need to solve.”

• To oversee a health innovation funding strategy that “ensures public money is focused on the areas of greatest impact for the NHS and patients.”

Blackwood presented the changes at today’s conference of the Association of the British Pharmaceutical Industry, one of the member organizations of the AAC. Speaking ahead of the event, ABPI CEO Mike Thompson said: “This is a real step forward in mak-

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exclusive online contentCO V E R UK Plan To Speed Access To ‘Cutting-Edge’ Products

R E G U L ATO RY U P D AT E 4 ABPI Exec Lauds Innovation And Access Provisions

In New UK Voluntary Scheme

8 Real-World Evidence: Observational Studies Deserve More Respect In US FDA Framework

10 Canada Develops RWE Guide Anticipating Increased Submissions

D R U G S A F E T Y 6 US FDA Converges With Other Regulators On Insomnia

Drug Warnings, But Broader Safety Disagreements Persist

C L I N I C A L T R I A L S 11 Indian Guide Offers Consolidated Advice

On New Clinical Trial Requirements

N E W P R O D U C T S 11 ViiV’s Potential HIV Blockbuster Among Latest Drugs

To Win EMA Nod

R E I M B U R S E M E N T 14 Medicare Part D Spending in 2019 Lower Than Expected

Because Of Rebates

15 Medicine Price Transparency Under Scrutiny At Next World Health Assembly

16 Novel Procurement Deal To Rid England Of Hepatitis C

A D V I S O RY CO M M I T T E E S 18 Recent And Upcoming US FDA Advisory Committees

inside: 11 cover 10

Ammunition Against ‘Medicare For All’? CBO Notes Possible Threats To Drug Accesshttps://pink.pharmaintelligence.informa.com/PS125223

Congressional Budget Office describes possible approaches to pricing prescription drugs, and how access might be affected, under a single-payer health care system in the US.

ANDA Modifications: US FDA Wants More Formal Facility-Initiated Withdrawalshttps://pink.pharmaintelligence.informa.com/PS125121

Facilities that cannot coax an ANDA sponsor to amend their application to exclude a center will have to convince a “less comfortable” FDA with a larger record.

Fresh Funds For Trials Of Novartis’s Novel Malaria Combo In Africahttps://pink.pharmaintelligence.informa.com/PS125202

New funding has been provided for more trials of Novartis’s combination malaria treatment in west and central Africa, adding to ongoing efforts to tackle the disease on the continent.

Next IMI Projects To Include Advanced Therapies And CAR-Tshttps://pink.pharmaintelligence.informa.com/PS125186

Advanced therapy medicinal products, CAR-Ts and patient-reported outcomes are among the topics that are expected to be the subject of the next round of calls by Europe’s Innovative Medicines Initiative.

Two More Member States Join US-EU Inspections Dealhttps://pink.pharmaintelligence.informa.com/PS125208

The number of European countries whose drug manufacturing site inspections the US regulator can rely on in place of its own inspections has grown.

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4 | Pink Sheet | May 6, 2019 © Informa UK Ltd 2019

R E G U L AT O R Y U P D AT E

ing sure UK patients get the latest breakthrough treatments. It sends a clear message that the UK intends to build an innovation-led economy alongside a more productive, innovation-ready NHS. We fully support Sam Roberts in making this a huge success that will change the lives of patients in the UK.”

HOW THE AAC WORKSAccording to health technology assessment body NICE, which hosts the AAC’s secretariat, key areas of interest for the collabora-tive include products that have evidence of clinical and cost effec-tiveness, address a significant unmet need, treat large populations or have a high budget impact, or enable a novel mode of action or “significant changes to the care pathway.”

Products designated as high potential will receive additional support, advice and direction from the AAC, with a “tailored package of support with dedicated case management,” NICE says. This support includes running processes in parallel, gener-ating real-world evidence, the potential for flexible commercial arrangements, and pathway transformation to drive adoption of products by the NHS.

Last year, the AAC identified 12 “rapid uptake” products in seven high-potential technology areas that were to be made available more quickly to enable patients with conditions such as cancer, heart disease and multiple sclerosis to gain early access to them.

NHS England said that these products “could improve the lives of around 500,000 patients and save the NHS up to £30m.”

They include the following:

• Sanofi’s alirocumab and Amgen’s evolocumab for primary hypercholesterolemia and mixed dyslipidemia: two “cost-effective” drugs that significantly lower cholesterol.

• Merck’s Mavenclad (cladribine) for highly active relapsing-remitting multiple sclerosis: “A drug for multiple sclerosis with a novel mode of action, high efficacy and a low treatment and monitoring burden.”

• A range of tests for heart blood flow analysis, suspected pre-eclampsia, myocardial infarction, colorectal cancer and benign prostatic hyperplasia.

The AAC was launched last year in response to the independently chaired Accelerated Access Review published in 2016, with the aim of making the process of getting transformative technologies to pa-tients quicker, cheaper and easy for both innovators and the NHS.

Its member organizations include the ABPI, the BioIndustry Association, the Association of Medical Research Charities, NHS England, and the UK medtech industry group, the Association of British HealthTech Industries.

Published online 2 May 2019

CONTINUED FROM COVER

ABPI Exec Lauds Innovation And Access Provisions In New UK Voluntary SchemeIAN SCHOFIELD [email protected]

O ne of the most important features of the new UK volun-tary scheme for branded medicines pricing and access (VPAS) is an enhanced horizon scanning and planning process that is expected to help the national health service pre-pare more effectively for the arrival of highly innovative treatments such as gene and cell therapies.

The scheme will also give companies and the NHS the flexibility to agree on more “creative” commercial arrangements that could enable earlier patient access to truly innovative new drugs, as well as help to identify the key new treatments that offer the most sig-nificant health gains for the population.

Like its predecessor, the Pharmaceutical Price Regulation Scheme, the new voluntary scheme was negotiated by the Associ-ation of the British Pharmaceutical Industry and the Department of Health and Social Care. It covers all branded medicines used on the national health service. (Also see “New UK Price Deal To Save NHS £930m & Speed Up Access To Innovation” - Pink Sheet, 26 Nov, 2018.)

Nearly four months after the scheme took effect at the begin-ning of this year, industry and government speakers at a Westmin-

mailto:[email protected]



ster Health Forum meeting in London last week discussed its key aspects and potential benefits for industry, the NHS and patients.

Paul Catchpole, director of value and access at the ABPI, outlined the objectives of the scheme and its key provisions, noting that it was intended to support innovation and the life sciences industry while offering value for money and financial stability for the NHS.

He said that the UK was “probably the leading country in Eu-rope” in terms of horizon scanning, but that the mechanism was built mostly around the needs of health technology assessment (HTA) bodies and “did not hardwire the NHS in those dialogues.” The aim, he said, was to bring in NHS England and the NHS more broadly so as to allow them to “plan for better introduction” of new therapies.

Speaking with the Pink Sheet after the meeting, Catchpole said that the enhanced horizon scanning feature was a key aspect of the new scheme in terms of improving access to new drugs, and that it would build upon the existing UK PharmaScan database of medicines in development.

PharmaScan, which allows companies with drugs in develop-ment to put information into the database, was originally de-signed mainly for use by the health technology assessment bod-ies to help them with their forward planning, “and it has worked really well,” Catchpole said. “But over the years we learned that you have to involve all players in the system, given the end-to-end pathways that we are trying to create for new medicines.”

Industry and the DHSC therefore agreed that there was “a real opportunity in this current scheme for us to work with NHSE on defining the really useful information that is needed to do good horizon scanning, and once we have done that to further develop UK PharmaScan.”

He stressed that it was not just about the database itself, but about defining the processes that need to be put in place to bet-ter integrate horizon scanning with the NHS’s business, service and budgetary planning systems. “The new scheme gives us the chance to look more widely at how we can better align with NHS service planning, and how we can get NHSE and the NHS more broadly involved earlier on in that process.”

A good example of how this can work, he said, was the way

that the CAR-T therapies were dealt with. As they are personal-ized treatments involving the extraction, treatment and return of the patients’ cells, they require “huge amounts of work” setting up the procedures in NHS Trusts, the services and pathways that are needed to introduce them, and “it takes time to get all this in place.” With the Gilead and Novartis products, Catchpole said, “the only way that could happen was to start work very early in NHSE and the Trusts on planning services and pathways.”

That, he said, was “a good example of where everyone got to-gether earlier than normal” instead of working in sequence – reg-ulatory issues followed by appraisal by the HTA body NICE, then NHS commissioning – these stages can be done more in paral-lel “so that everything is ready for when the medicine becomes available.” The two CAR-T therapies, Gilead’s Yescarta and Novar-tis’s Kymriah, were a good example, he said: once the NICE guid-ance was complete, “everything was ready for their introduction.”

Areas that could most benefit from this approach, Catchpole said, included cell and gene therapies, where a great deal of ser-vice and pathway planning would be needed. “Not everything will need it, but some disease areas and types of treatment could benefit.”

MORE COMMERCIAL FLEXIBILITIESAnother key focus of the scheme is to offer greater “commercial flexibilities” for the most cost-effective new medicines, building on existing arrangements like patient access schemes (PASs) and the Cancer Drugs Fund but going further and offering “enhanced commercial arrangements” for “value propositions at even greater levels of cost effectiveness, plus any applicable QALY [quality-ad-justed life year] weightings.”

Asked to elaborate on what this might mean in practice, Catch-pole noted that the previous two PPRSs had a mechanism for com-mercial flexibility in the form of PASs, from simple discounts to more complex schemes.

However, he said this mechanism was “quite rigid” in terms of what form these schemes could take, so “the thinking now is that in order to match the high level of innovation in new medicines coming down pipelines, we need to be more creative in allowing companies to come up with very innovative access proposals.”

This would involve “making sure we have the right processes to allow companies to work with NHSE and NICE on co-designing these schemes, with less rigidity on what they might be, in order to unleash some more creative thinking about the sorts of solutions that might be required in the future.”

“We have intentionally left it open,” Catchpole said, although he added that “everyone knows the sort of things we are thinking about – outcomes-based payment schemes where you collect pa-tient outcomes and are reimbursed on those rather than on the price of the drug. That kind of arrangement is quite exciting and might also be more suited to new innovations in the pipeline, such as in gene therapy, which is a one-off, high-cost treatment. This is an area where innovative payment schemes could come in, where you are paying for outcomes achieved in each year. These are the kinds of things we are thinking about.”

Catchpole said that the enhanced horizon scanning

feature is a key aspect of the new scheme and would build upon the existing UK

PharmaScan database.

pink.pharmamedtechbi.com



Catchpole also noted that the ABPI, NHSE and the DHSC are working on a set of metrics that can be used to monitor the overall effectiveness of the new scheme “to see if we are going in the right direction. We have to come up with some creative metrics in the access and uptake area, so hopefully we will have a nice suite of measures that will allow progress to be moni-tored in totality.”

GREATEST HEALTH GAINSA third aspect of the scheme highlighted by Catchpole was the decision to identify the five products or product groups that offer the greatest health gains for the population, and to take action to boost their use. The official target is to reach the “upper quartile of uptake” of these products in relation to their uptake in comparator countries.

“This is another really important commitment that we are very excited about,” the ABPI executive said. “We won’t do it for everything because we can’t accelerate everything – but are there some groups of medicines that are really making a difference, perhaps because they are in disease areas with a large unmet need or that place a high burden on the NHS.”

Once the products have been identified, “we will look at what comparable countries are doing and compare that with the UK, and see whether we can draw some lessons and im-prove uptake and access. This is a new thing we haven’t done before and it has opened up an interesting debate.”

“We are now moving into implementation mode,” Catch-pole continued. “It is not a straightforward job, so the chal-lenge we are working through with NHSE is thinking about how we identify these areas and the types of medicines.”

He stressed that it was not just about cost effectiveness or value for money. “A medicine might be great value for mon-ey, but it might not necessarily be a product that you want to drive uptake for. It is also a function of the health benefit at a population level, and which products are showing the biggest health benefit for the population. It is a new way of thinking and we have to come up with a rational approach for doing it.”

The idea is that the products should have been identified by NHSE, and their usage boosted, half-way through the five-year life of the new scheme. “So basically we have two and a half years to do the job and move the needle on usage,” Catchpole said. Identification of the products would need to happen “reasonably quickly” – hopefully within two or three months’ time.

NICE ASPECTSThe new scheme also provides for all new active substances or major new indications to undergo a NICE appraisal unless there is a clear rationale for not doing so. In addition, the accelerated assessment times that are already in place for cancer drugs will be matched for non-oncology drugs as far as possible.

Published online 29 April 2019

US FDA Converges With Other Regulators On Insomnia Drug Warnings, But Broader Safety Disagreements PersistMICHAEL CIPRIANO [email protected]

D espite a broader trend of disagreement among national pharma regulators over instances for which to issue drug safety alerts, there appears to be some degree of convergence on warnings regarding certain insomnia drugs.

The US Food and Drug Administration issued a drug safety communication on 30 April announcing that it would be adding boxed warnings to the labels and Medication Guides of certain Rx insomnia drugs following reports of serious injury or death resulting from complex sleep behaviors exhibited by patients on these medications.

The impacted drugs, which include eszopiclone (Sunovion Pharmaceuticals Inc.’s Lunesta), zaleplon (Pfizer Inc.’s Sonata), and zolpidem (Sanofi’s Ambien, Orexo AB’s Edluar, Purdue Pharma LP’s Intermezzo, and Aytu BioScience Inc.’s Zolpimist), will also have contraindications added to their labels for patients who have previously experienced an episode of complex sleep behavior while on these products.

Using adverse event reports to the agency and medical liter-ature, the FDA identified 66 cases of complex sleep behaviors, such as sleepwalking, sleep driving and unsafely using a stove, occurring with these drugs over the past 26 years that have led to serious injury, including 20 instances of death.

“These cases included accidental overdoses, falls, burns, near drowning, exposure to extreme cold temperatures leading to loss of limb, carbon monoxide poisoning, drowning, hypother-mia, motor vehicle collisions with the patient driving, and self-injuries such as gunshot wounds and apparent suicide attempts,” the FDA said.

Lunesta previously had its labeling updated to include a lower starting dose and language cautioning against driving or other activities that require complete mental alertness for those taking a higher dose. (Also see “Merck Insomnia Drug Belsomra Has Warn-ing That It Makes You Sleepy” - Pink Sheet, 14 Aug, 2014.)

SIMILAR STEPS FROM OTHER REGULATORS … The FDA appears to be achieving some degree of convergence with other national drug regulators in this instance.

The Australian Therapeutic Goods Administration, for in-stance, issued a safety alert in February 2008 announcing that it

D R U G S A F E T Y



added a boxed warning to documents pertaining to zolpidem fol-lowing reports of “bizarre and sometimes dangerous sleep related behaviours such as sleep walking and sleep driving in some users of zolpidem.”

According to the TGA, there had been 1,032 Australian reports of suspected reactions to zolpidem products entered into the agency’s adverse reactions database, including 687 of these reports being en-tered just within the preceding 12 months.

The boxed warning states that “Zolpidem may be associated with potentially dangerous complex sleep-related behaviours which may include sleep walking, sleep driving and other bizarre behaviours. … Caution is needed with other CNS depressant drugs. Limit use to four weeks maximum under close medical supervision.”

Similarly, Health Canada published a safety communication related to zolpidem. When zolpidem was first approved in Canada in 2011 under the brand name Sublinox, the agency issued an alert noting that, “On the international market, zolpidem has been reported in as-sociation with cases of complex sleep behaviours, where people rise from bed while not fully awake and engage unknowingly in activities which they do not remember doing the following morning, such as driving a car, leaving the house, eating food and making phone calls. Complex sleep behaviours are rare but potentially dangerous.”

And in 2009, Health Canada also raised the alarm about complex sleep behaviors in a series of insomnia drugs, including zolpidem and zaleplon. Although both drugs were not yet approved (zaleplon was

cleared under the brand name Starnoc in 2010), the regulator noted that they may become available in the future and that their labels would contain the safety information.

… BUT NOT A BROADER TRENDBut this instance of convergence does not appear to be indicative of a broader trend.

A 29 April research letter published in JAMA Internal Medicine found that the FDA, Health Canada, the TGA and the UK Medicines and Healthcare products Regulatory Agency rarely ever issue safe-ty advisories that cover the same drug risk issue.

Specifically, the analysis, which examined the period from 2007-2016, identified 1,441 advisories across the four countries covering 680 drug-risk issues. Of the 680 drug issues, only 70 times (10.3%) did regulators issue advisories in every country where the drug was market. There were also 573 issues where all four countries approved the drug, and only 40 times (7%) did all four regulators publish an advisory on the issue. (See graphic.)

The researchers, led by corresponding author Barbara Mintzes from the University of Sydney, write that the results likely reflect differences in each country’s approach to pharmacovigilance.

“National medicines policy determines the activities of the medi-cines regulator and resource availability, including the capacity to undertake postmarket monitoring and its administrative burden,” the research letter says.

The analysis also found that the MHRA was the most likely to release

a safety alert for drug risk issues, while the TGA was the least likely.

SHARPLESS BECOMING ACTIVE IN COMMUNICATIONSIt already appears that recently-departed FDA commissioner Scott Gottlieb has set a precedent for his successors. Gottlieb became known during his time at the FDA for the frequency which he was personally quoted in the agency’s press releases.

Now, acting commissioner Norman Sharpless is picking up right where Gottlieb left off, as the former National Cancer Institute head has been quoted already in two FDA announcements in just his first few weeks on the job.

The agency concurrently issued a press release quoting Sharpless with the insomnia drug safety communication, who commented that “While these incidents [of complex sleep behavior] are rare, they are serious and it’s important that patients and health care professionals are aware of the risk. These incidents can occur after the first dose of these sleep medicines or after a longer period of treatment, and can occur in patients without any history of these behaviors and even at the lowest recommended doses.”

Sharpless also issued a joint statement with deputy commission-er Frank Yiannas on 30 April on food safety. It similarly took close to a month for Gottlieb to be personally quoted in a release as well following his swearing in as commissioner. (Also see “US FDA Com-munications Post-Gottlieb: No Slow-Down In Statements, But Attri-bution Changes “ - Pink Sheet, 28 Apr, 2019.)

Published online 1 May 2019

Level Of Concordance Among Regulators In Releasing Safety Warnings

Each shape indicates the number of drug-risk issues for which regulators have issued advisories.The chart includes 573 drug-risk issues for which all four regulators had approved the drug.

Source: JAMA Internal Medicine

D R U G S A F E T Y

FDA TGA

HC MHRA

122

89 69

136

50

48

40

14

27 21

25 4

15

9 11

pink.pharmamedtechbi.comadvisories.The



REAL-WORLD EVIDENCE: Observational Studies Deserve More Respect In US FDA FrameworkSUE SUTTER [email protected]

T he US Food and Drug Administra-tion should take a more welcoming view on the use of observational studies to support new efficacy claims for approved drugs, the pharmaceutical in-dustry believes.

Concerns about bias and the lack of randomization in observational studies need not derail the use of such real-world evidence to support efficacy claims but, rather, can be addressed through avail-able methods of bias reduction, industry representatives said in comments on the agency’s RWE framework.

By using these methods, “FDA can, in appropriate cases, achieve confidence in the RWE generated from non-randomized observational data,” the Pharmaceutical Research and Manufacturers of America’s comments state.

While the pharmaceutical industry is urging the FDA to open the door wider to reliance on observational studies, includ-ing non-randomized designs, insurer Kai-ser Permanente is pushing the agency to maintain a narrow opening given the limi-tations in the real-world data sources used for such studies.

FDA’S CAUTIOUS VIEW …Released in December, the framework was a deliverable under the 21st Century Cures Act, which directed the agency to explore how RWE can be used to support approval of new indications for existing drugs and to satisfy post-approval study requirements.

The framework defines RWD and RWE, explains the scope of the RWE program un-der Cures, and details considerations for use of RWD/RWE in making decisions about the effectiveness of drugs and biologics.

It also lists a host of guidance documents the agency plans to issue or is considering publishing, including one on observa-tional study designs using RWD. (Also see “Real-World Evidence: US FDA Framework Emphasizes Data Fitness And Study Qual-

ity” - Pink Sheet, 9 Dec, 2018.)The framework reflects the FDA’s long-

standing cautious view on the use of ob-servational studies to support drug efficacy claims. (Also see “US FDA Is Hesitant About Using Observational Studies In Real-World Evi-dence Framework “ - Pink Sheet, 6 Dec, 2018.)

This wariness stems from a number of factors, including the potential for bias resulting from non-random treatment assignment, particularly in retrospective

observational studies, and the risk that sponsors will keep repeating studies with slightly altered parameters until they get their desired result.

However, industry comments suggest these concerns are surmountable.

… DOES NOT SIT WELL WITH INDUSTRYThe FDA should “work creatively to embrace use of RWD – and observational data in particular – to generate RWE that supports regulatory decision-making,” PhRMA said.

The trade association highlights advan-tages of observational data relative to clini-cal trial data.

“Observational RWE can better reflect the broader patient populations, settings, and drug uses that are typical of clinical prac-tice,” the group said. “Well-designed obser-vational RWE studies can be conducted in a much more cost-effective and efficient way than traditional randomized clinical trials.”

All study designs, whether observational or randomized, may be susceptible to se-lection and measurement bias, and ran-domization is not the only suitable method to reduce bias, PhRMA said, asserting that non-randomized observational data may generate RWE acceptable for regulatory de-cision-making on treatment effectiveness.

“Fortunately, there is emerging consen-sus regarding methodological standards and good procedural practices for obser-vational studies of treatment effectiveness and safety,” PhRMA said.

“There are multiple methods capable of reducing bias and other concerns about us-ing non-randomized observational data to generate RWE,” the comments state. “Exist-ing study design approaches (e.g., new user design and active comparator) and statisti-cal methods (e.g., propensity score analysis, marginal structural models, and instrumen-tal variable analysis) can address potential biased estimates of treatment effect.

“Additionally, the academic literature de-

“PhRMA urges the FDA to consider methods

beyond randomization when looking to define acceptable methods to increase the confidence in efficacy claims from observational data.”




scribes several conditions that increase the confidence in the validity of observational research results demonstrating a potential cause of treatment effect,” PhRMA said.

The FDA has previously accepted such methods to support regulatory decisions based on observational safety studies, which also have the potential for bias and confounding due to lack of randomization, PhRMA said.

“With the availability of methods and conditions to reduce bias when using non-randomized observational data to estab-lish causal inferences, PhRMA urges the FDA to consider methods beyond random-ization when looking to define acceptable methods to increase the confidence in ef-ficacy claims from observational data.”

The Biotechnology Innovation Organi-zation’s comments echo those of PhRMA. However, BIO also calls on the FDA to convene a public workshop focused on methodologies for observational studies and their applications to different study designs incorporating RWD.

TRIAL REPLICATION PROJECTSUnder its RWE program, the FDA is assess-ing whether rigorously designed observa-tional studies using existing electronic ad-ministrative health care data can replicate the results from approximately 30 com-pleted Phase III randomized controlled trials. (Also see “Real-World Data Could Get Boost From Trial Replication Project” - Pink

Sheet, 26 Apr, 2018.)The project, RCT DUPLICATE, is being

conducted in partnership with Brigham and Women’s Hospital and recently was expanded to include seven Phase IV trials that currently are ongoing. The replication effort is one of several RWE demonstration programs underway at the agency. (Also see “Real-World Evidence Demo Projects From US FDA To Include New Mobile App” - Pink Sheet, 6 Nov, 2018.)

The Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Har-vard, in partnership with OptumLabs, also has initiated a project known as OPERAND that will use retrospective observational data to determine if results can confirm previously published randomized clinical trial results.

Comments from ISPOR, the professional society for health economics and out-comes research, say that while such trial replication efforts are important, “some level of variation in results can be expected even among the most rigorously designed and conducted observational study and a corresponding RCT.”

“Accordingly, additional insight is need-ed into the agency’s thinking on what is an ‘acceptable’ level of variation as well as what the additional quantity of such ef-forts the agency would like to see and who should conduct these analyses,” ISPOR’s comments state.

Janssen R&D LLC’s comments raise questions about the hypotheses and study design methods for the agency’s trial rep-lication project, including how feasibility of trial replication is assessed and which randomized, controlled trials will be the subject of replication efforts.

“What kinds of statistical approaches will be used to address potential confounding in the RWE studies?” Janssen’s comments ask. “What are the metrics for ‘agreement’ between RCT and RWE results? How much heterogeneity is tolerated to allow for the assessment of ‘replication’ considering dif-ferences in design and populations?”

A CALL FOR STRICT CRITERIA, INCLUDING RANDOMIZATIONIn a stark divergence from the views ex-pressed by pharma industry comments,

insurer Kaiser Permanent urged the FDA to set very strict criteria for RWE study designs that can be used to support approval of new indications, saying: “In general, randomized study designs using RWE would be best.”

Single-arm studies with an external RWD control and observational designs are particularly problematic, Kaiser said. “These designs are subject to numerous potential sources of confounding and bias, not all of which can be controlled for, par-ticularly in retrospective designs based on historical control using sources such as charts, claims data and medical records.

“Observational designs are better-suited to reveal correlations rather than causa-tion and are therefore unlikely to consti-tute substantial evidence in the absence of

more robust studies,” the comments state.Electronic health records, claims data,

charts, registries and other sources of ob-servational data present inconsistencies, confounders and biases that either do not exist, or are well-controlled, in randomized clinical trials, the insurer said.

“The intended function of an original data source will limit its utility and validity for supporting approvals of new indica-tions,” Kaiser said. Electronic health record and claims data “lack complete informa-tion about clinical events of interest that are not documented for billing or even pa-tient care purposes.”


Additional insight is needed into the agency’s

thinking on what is an “acceptable” level of variation in results

between a randomized clinical trial and an

observational study, ISPOR said.

“Observational designs are better-suited to

reveal correlations rather than causation and are

therefore unlikely to constitute substantial

evidence in the absence of more robust studies.”

– Kaiser Permanente

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Canada Develops RWE Guide Anticipating Increased SubmissionsVIBHA SHARMA [email protected]

H ealth Canada has developed a guidance document to help drug sponsors generate real-world evidence (RWE) that is consistent with the regulatory standard of evidence in place in Canada and internationally.

The guidance document includes an overview of some of the issues that spon-sors should address in protocol develop-ment, and characterizes some of the data quality concerns observed within submis-sions containing RWE, the government de-partment explained.

Entitled “Elements of Real World Data/Evidence Quality throughout the Drug Life Cycle,” the document is expected to help companies that are considering using RWE in their drug submission collect and submit high-quality RWE that meets the evidence requirements for approval.

Sponsors seeking to use RWE in a drug submission to Health Canada, particularly if it is to be used as pivotal evidence, should refer to this document, the department said. The expectation is that new drug submis-sions containing RWE will clearly report the various elements outlined in the guide, and that “justification and appropriate rationale for their omission will be provided,” it added.

Health Canada said that while it already reviews drug submissions that include evi-dence gathered from real-life settings, es-

pecially in the field of cancer, it expects to receive new submissions in areas such as pediatrics in the future. The guidance docu-ment has therefore been developed to fa-cilitate drug submissions that include RWE.

The document has been issued as part of ongoing efforts by Health Canada to optimize the use of RWE for regulatory de-cisions “to improve the extent and rate of access to prescription drugs in Canada.” A project on “Strengthening the Use of Real World Evidence for Drugs” has been devel-oped to achieve this goal and the depart-ment is currently working with industry and health technology assessment (HTA) bodies to establish an approach to using RWE “across the drug life cycle that is both systematic and transparent.”

As part of these plans, Health Canada also intends to issue another document later this year on how to optimize and formalize the use of RWE across the life cycle of a drug. For this, the department explained that it has collaborated with its HTA partners – the Canadian Agency for Drugs and Technologies in Health, and the Institut national d’excellence en santé et en services sociaux (INESSS). “Lessons learned from this collaborative approach will be shared with partners both in Canada and internationally,” it said.

Under the initiative, the department is

also inviting high-quality, RWE submis-sions from industry:

• That aim to expand evidence-based indications for populations often excluded from clinical trials, such as children, elderly and pregnant women.

• For drugs/diseases where clinical trials are unfeasible, such as rare diseases.

• Where clinical trials are unethical, such as during emergencies where dosages from animal studies may need to be extrapolated to treat humans potentially exposed to chemical or biological threats.

QUALITY OF RWEThe quality of RWE evidence – which is de-termined by factors such as data reliability and validity, scientific question of inter-est, study design, statistical methods and analysis, and interpretation of results – in-forms the extent to which Health Canada considers such information in regulatory decision-making.

In its new guidance document, Health Canada has listed 15 key elements that it says should be considered by sponsors for each protocol. These elements are reflec-tive of the “checklist for study protocols” developed by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance and the International Society for Pharmacoepidemiology’s good practice guidance.

Health Canada suggests that both pro-spective and retrospective designs should attempt to address each element listed in the guide, or justification should be pro-vided on why these elements may not be applicable to the specific study. The de-partment said it would update the guid-ance document as its expertise and experi-ence in assessing RWE evolves.




C L I N I C A L T R I A L S

Indian Guide Offers Consolidated Advice On New Clinical Trial Requirements VIBHA SHARMA [email protected]

I ndia’s Central Drugs Standard Control Organization has issued a guidance doc-ument offering consolidated advice to the pharmaceutical industry on the “New Drugs and Clinical Trials Rules 2019” that were implemented in March.

The guidance document, issued in FAQ format, delves into various topics covered by the new rules, such as the introduction of strict timelines for granting permissions for clinical trials, bioavailability/bioequivalence studies and manufacturing of new drugs.

It also further elaborates on a key topic for foreign sponsors – the circumstances under which a waiver can be granted from the requirement to conduct local Phase III clinical trials to support the ap-proval of a new drug already approved in other countries. Industry experts had earlier commented that allowing such waivers was a step in the right direction as it could help speed up patient access and shorten launch timelines for new in-

novative therapies. In addition, the FAQ document clarifies

that the requirement to submit non-clinical and clinical data may be “relaxed, abbrevi-ated, omitted or deferred” on a case-by-case basis for drugs that target life-threatening, serious or rare diseases. This is also relevant for drugs intended to treat diseases of “spe-cial relevance to the Indian scenario,” those targeting unmet medical needs or for use in disaster or special defense circumstances (for example, drugs for hemostatic use and quick wound healing, products that can en-hance oxygen carrying capacity or address radiation safety, and medicines for combat-ing chemical, nuclear and biological inflic-tion, etc).

The document also elaborates on a new “accelerated approval process,” which may be allowed for a new drug for a disease or condition, taking into account its severity, rarity or prevalence and the availability or lack of alternative treatments, provided

that there is prima facie evidence that the product offers a meaningful therapeutic benefit over existing treatments.

It also offers details on a compassion-ate use program – created under the new rules – whereby government hospitals and medical institutions can import a drug that is not approved in India but is approved for marketing in the country of origin, for treating a patient suffering from a life-threatening disease, a disease that can cause serious permanent disability, or a disease requiring therapies for unmet medical needs. The FAQ document stresses that the compassionate use program does not cover investigational products and that only drugs approved for marketing in the country of origin can be imported for this purpose.

The full FAQ document, addressing 122 questions, is available online.


ViiV’s Potential HIV Blockbuster Among Latest Drugs To Win EMA Nod NEENA BRIZMOHUN [email protected]

T he European Medicines Agency has recommended that 13 drugs be approved for sale across the EU in-cluding ViiV Healthcare’s Dovato (dolute-gravir/lamivudine), a single-pill, two-drug regimen for HIV, for which a blockbuster future has been forecast.

Ultomiris (ravulizumab), Alexion Phar-maceuticals’ follow-up to its blockbuster paroxysmal nocturnal hemoglobinuria treatment, Soliris (eculizumab), was also among the products granted a positive opinion by the EMA, as were Novo Nord-

isk’s Esperoct (turoctocog alfa pegol), for treating hemophilia A, and Dova Pharma-ceuticals’ Doptelet (avatrombopag), for se-vere thrombocytopenia.

The EMA recommended against the ap-proval of one product – a hybrid medicine that Teva Pharmaceutical Industries sub-mitted for the treatment of prostate can-cer, Cabazitaxel Teva (cabazitaxel). Hybrid applications rely in part on the results of preclinical tests and clinical trials of an al-ready authorized reference product and in part on new data)

N E W P R O D U C T S

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All the recommendations were made by the agency’s Committee for Medicinal Products for Human Use (CHMP), which dis-cussed the marketing authorization applica-tions (MAAs) for the products during its 23-26 April meeting. (Also see “New EU Market Hopefuls Await Their Fate; EMA Re-Adopting Zynteglo Opinion “ - Pink Sheet, 25 Apr, 2019.)

The other products that received a posi-tive opinion included:

• Regeneron Pharmaceuticals’ Libtayo (cemiplimab), for treating advanced cutaneous squamous cell carcinoma. The CHMP recommended a conditional marketing authorization for this product.

• Molteni Farmaceutici’s Sixmo (bu-prenorphine), a long-lasting implant to treat opioid dependence.

• Evolus Pharma’s Nuceiva (botulinum toxin type a), for temporary improve-ment of vertical lines between the eyebrows.

• Pfizer’s Talzenna (talazoparib), for treating adult patients with germline BRCA1/2 mutations who have HER2-negative locally advanced or metastatic breast cancer.

• GlaxoSmithKline’s Temybric Ellipta (fluticasone furoate/umeclidinium/vilanterol), for the maintenance treat-ment of adult patients with moderate to severe chronic obstructive pulmo-nary disease. The MAA for this prod-uct was submitted as an informed consent application, which makes use of data from the dossier of a previ-ously authorized medicine, with the marketing authorization holder of that medicine giving consent for the use of their data in the application.

One biosimilar, two generics and a hy-drid medicine were also granted positive opinions. These were:

• Juta Pharma’s Grasustek (pegfilgrastim), for prophylaxis against neutropenia in adult patients treated with cytotoxic chemotherapy.

• Mylan’s Ambrisentan Mylan (ambrisentan), for treating pulmonary arterial hypertension.

• CIS bio international’s Striascan (ioflupane (123I)), a radiopharmaceutical for diagnosing Parkinson’s disease and other related diseases and dementia.

• Nova Laboratories’ Xromi (hydroxy-carbamide), for preventing vaso-occlu-sive complications of sickle cell disease in patients over two years of age.

In addition, the CHMP recommended an extension of therapeutic indication for As-traZeneca and MSD’s PARP inhibitor, Lyn-parza (olaparib), as a first-line maintenance treatment of BRCA-mutated advanced ovarian cancer.

BLUEBIRD AND LILLYAlso at its meeting, the committee re-adopted the positive opinion it had issued last month for bluebird bio’s first-of-a-kind gene therapy for transfu-sion-dependent β-thalassemia, Zynte-glo. Its re-adoption of the opinion fol-lowed an administrative request by the European Commission regarding Zynte-glo’s product information. Bluebird told the Pink Sheet that it does not expect the re-adoption to delay the product’s approval by the commission, which is still expected during Q2 2019.

In addition, the CHMP concluded its assessment of Eli Lilly’s ANNOUNCE study of the company’s soft tissue sar-coma treatment, Lartruvo (olaratum-ab), which Lilly last week said it was withdrawing from the market globally after the drug failed to confirm a sur-vival benefit in post-marketing studies. (Also see “A Successful Failure? Lartruvo’s Speedy Withdrawal Sets New Bar For Ac-celerated Approval Drugs” - Pink Sheet, 25 Apr, 2019.)

As expected, the CHMP said its as-sessment found that Lartruvo with doxorubicin did not prolong the lives

of patients with soft tissue cancer more than doxorubicin alone, and it recom-mended that the EU conditional mar-keting authorization for the medicine be revoked.

CHMP opinions are forwarded to the commission for the final say; these le-gally binding decisions should be made by the commission within 67 days.

A POTENTIAL BLOCKBUSTER FOR VIIV?ViiV Healthcare’s Dovato, if approved by the commission, will become Europe’s first once-daily, single-pill, complete two-drug regimen for treating treat-ment-naïve HIV patients, according to the company.

A blockbuster future has been forecast for the product, which was recently ap-proved in the US for patients who have never received antiretroviral treatment. Dovato is expected to challenge the widely used three-drug combination HIV therapies, particularly those marketed by key competitor Gilead Sciences.

The US Food and Drug Administration, when it approved the product on 8 April, noted that Dovato gave patients who have never received antiretroviral treat-

ment the option of taking a two-drug regimen in a single tablet while elimi-nating additional toxicity and potential drug interactions from a third drug.

Datamonitor Healthcare has forecast Dovato sales to increase gradually to $1.1bn in 2026 in the five major EU mar-kets and the US. However, Biomedtracker analysts have warned that there may be residual physician concerns about the potential emergence of resistance af-ter long-term use, particularly in non-compliant patients, and the need for the new therapy to gain recommended sta-tus in treatment guidelines, which could

ViiV’s Dovato, if approved by the commission, will become Europe’s first once-daily, single-pill, complete two-drug regimen for treating treatment-naive HIV patients.



dampen its uptake.ViiV said that the CHMP’s recommen-

dation was based on the company’s landmark GEMINI 1 & 2 studies, which demonstrated non-inferior efficacy of dolutegravir + lamivudine compared with a traditional dolutegravir-based, three-drug regimen, in HIV-1 infected, treatment-naïve adults. It added that “no patient who experienced virologic fail-ure in either treatment arm developed treatment-emergent resistance.”

The CHMP’s recommendation covers the use of Dovato for treating HIV-1 infec-tion in adults and adolescents above 12 years of age weighing at least 40kg, with no known or suspected resistance to the integrase inhibitor class or to lamivudine.

ULTOMIRIS A NEW STANDARD OF CAREAlexion’s Ultomiris is the first and only long-acting C5 complement inhibitor and it could become the new standard of care for patients with paroxysmal nocturnal he-moglobinuria (PNH), the company said.

Ultomiris is administered every eight weeks, compared with Alexion’s aging complement inhibitor Soliris, which is ad-ministered once a week for the first four weeks, followed by a higher dose the next week, repeated every two weeks.

The CHMP has recommended Ultomiris be approved for the treatment of adult pa-tients with PNH with hemolysis and clinical symptoms indicative of high disease activ-

ity, and also for adult patients who are clin-ically stable after having been treated with Soliris for at least the previous six months.

Ultomiris has EU orphan drug designa-tion. It was approved for sale in the US in December 2018. (Also see “Keeping Track Of The US FDA’s Final Approvals Of 2018” - Pink Sheet, 2 Jan, 2019.)

ESPEROCT AND DOPTELETEsperoct, which also has EU orphan drug designation, is a long-acting Factor VIII re-placement therapy for hemophilia A. Novo is seeking to use it for the treatment and prophylaxis of bleeding in patients 12 years and above. The CHMP’s recommendation was based on the results from the largest pre-registration clinical program conduct-ed in hemophilia A, with the inclusion of 270 previously treated people with severe hemophilia A and more than five years of clinical exposure, the company said.

Esperoct was approved in the US in Feb-ruary, but its launch is being delayed until 2020 because of a patent deal the firm made. (Also see “Keeping Track: US FDA Ap-proves Esperoct, Tightens Chantix Label, Starts Review Of Alder’s CGRP Candidate “ - Pink Sheet, 24 Feb, 2019.)

As for Dova’s product, Doptelet has been recommended by the CHMP for treating severe thrombocytopenia in adult patients with chronic liver disease who are sched-uled to undergo an invasive procedure.

The product is a second generation, orally administered thrombopoietin receptor ago-

nist. It was approved in the US in May 2018.

WHY TEVA FAILED TO MAKE THE GRADERegarding the negative opinion the CHMP adopted for Cabazitaxel Teva, the EMA noted that because the product had been developed as a hybrid medicine, Teva had presented data from the published litera-ture to demonstrate that it was similar to Jevtana, and the company had also made reference to another medicine, Taxotere, which contains docetaxel.

“The CHMP did not agree that the data presented by the company were sufficient to support the claim that cabazitaxel and docetaxel should be considered the same active substance,” the EMA said. “Although cabazitaxel is a derivative of docetaxel, laboratory studies have shown that caba-zitaxel and docetaxel have different prop-erties, for example cabazitaxel can cross the blood-brain barrier while docetaxel cannot,” the agency explained.

“Additionally, laboratory data suggest that cabazitaxel can be effective at treat-ing cancer that is resistant to docetaxel. Data from clinical studies also showed differences in the safety profile of the two active substances. Furthermore, pa-tients receiving cabazitaxel are exposed to the unchanged substance plus two ac-tive breakdown products, which are not formed when docetaxel is given.”


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R E I M B U R S E M E N T

Medicare Part D Spending in 2019 Lower Than Expected Because Of Rebates CATHY KELLY [email protected]

S pending on Medicare Part D benefits will total $97.7bn in 2019, accord-ing to the latest Medicare Trustees Report, which is lower than the $103.3bn previously projected.

The spending estimate for 2019 has been reduced “primarily because of high-er rebates and slower overall drug price increases assumed in the short-range period in this year’s report,” according to the 2019 report, released 22 April. (Also see “Medicare Part D Spending Projected To Decline in 2018 As Rebates Increase” - Pink Sheet, 7 Jun, 2018.)

The trustees reiterate the expectation from previous reports that prescription drug rebates will become an increasingly important source of revenue for Medicare Part D plans in the coming years. They estimate rebates will grow steadily from an average of 25.3% of total drug costs in 2018 to more than 29% of costs in 2028. (See charts.)

Even with rebates, per capita drug costs are expected to increase an average of 4.9% annually over the next 10 years, up from an average of 3.2% annually over the past 10 years. Spending on Part D benefits will surge by more than $100bn between 2019 and 2028, according to the report.

The accelerated growth will result from a slowdown in generic drug dispensing and an ongoing increase in specialty drug costs, the report explains.

The report does not address the Admin-istration’s proposal to eliminate rebates in Medicare Part D, which could dramatically change the financials in the Part D pro-gram. (Also see “HHS Rebate Plan A Leap Of Faith? Lower Costs Hinge On Drug Firm, Plan Response” - Pink Sheet, 2 Feb, 2019.)

Part D plan sponsors and pharmacy ben-efit managers strongly object to the change, arguing it will lead to higher costs for plans, which will result in significant premium increases. Nevertheless, HHS is hoping to implement the rule beginning in 2020.

Trustees Highlight Part D Reliance On RebatesRebates as a percentage of costs expected to grow.

Source: 2019 Medicare Trustees Report

Part D Aggregate Benefit Spending ProjectionsIncrease of more than $100bn expected over next 10 years.

Source: 2019 Medicare Trustees Report

25.0

25.5

26.0

26.5

27.0

27.5

28.0

28.5

29.0

29.5

2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028

Reba

tes

Of N

et D

rug

Cost

s (%

)

200

180

160

140

120

100

80

60

40

20

02019 2020 2021 2022 2023 2024 2025 2026 2027 2028




REPORT UNDERSCORES IMPORTANCE OF REBATES, PAYERS SAYPayers described the Trustees report as further evidence that the proposed rule would not work as hoped to lower drug prices.

“The report’s projections on Part D reinforce our position that the rebate rule would hurt seniors, increase pre-miums and raise taxpayer spending – all while creating a windfall for drug makers,” America’s Health Insurance Plans said in an email.

“The consequences of eliminating a negotiating tool that is holding down drug prices for seniors, and relying on the hope that drug makers will lower prices on their own, are significant and concerning.”

Similarly, the Pharmaceutical Care Management Association maintained “the findings in the 2019 Medicare Trustees report confirm that one im-portant way pharmacy benefit man-agers are controlling Medicare Part D drug costs is through negotiations with drug makers for price conces-sions, or rebates.”

The group added it is “concerned that the Administration’s proposed rule … will cause disruption to the Part D ben-efit and the drug supply chain should PBMs’ ability to effectively negotiate and facilitate price concessions be di-minished.”

Nevertheless, PCMA added that if HHS moves ahead with implementa-tion, “PBMs have the infrastructure, tools, and data to best operationalize a restructured system.” (Also see “HHS Rebate Reform: An Air Of Inevitability In Stakeholder Comments “ - Pink Sheet, 22 Apr, 2019.)


Medicine Price Transparency Under Scrutiny At Next World Health Assembly FRANCESCA BRUCE [email protected]

A resolution calling on World Health Organization member states to work together on increasing transparency in medicine pricing is likely to be debated at the next World Health Assembly later in the month. The resolu-tion has been tabled by Italy, and has sup-port from other European countries.

The aim of the resolution is to give the WHO director general “an authoritative mandate” to strengthen the organiza-tion’s work on the transparency of drug and vaccine prices and related areas such as R&D costs, said Italy’s health minister, Giulia Grillo, in a letter to the WHO direc-tor general.

In the letter, Grillo says that interna-tional action is necessary to “improve the transparency in the reporting of prices, R&D costs and production costs of medicines and vaccines, including public sources.”

A first draft of the resolution was sub-mitted in February, and has since garnered the support of some 83 civil society orga-nizations, including Knowledge Ecology International, Médecins Sans Frontières Access Campaign, Non Communicable Disease Alliance of Kenya, Prescrire and Health Action International. The organiza-tions signed an open letter to the WHO, highlighting “deplorable asymmetries of access to information” relating to innova-tion and the medicines supply chain.

“This is a critical time for governments to consider reforms in pricing and incen-

tives for innovation for health technolo-gies. The transparency measures pro-posed in the resolution will ensure that consideration of such reforms will be based upon the best possible evidence,” said the open letter.

However, the pharmaceutical industry is unlikely to support the resolution. In-dustry claims that confidentiality allows companies to adapt their prices depend-ing on the specifics of different countries, such as disease prevalence and the nature of the health system. For example, it helps companies offer preferential prices to lower-income countries. Industry has also warned that transparent prices could also dissuade some companies from launch-ing in some markets if they believe prices will be impacted elsewhere, for example because of reference pricing.

NEW INCENTIVESThe resolution, which has been updated since February, urges member states to “undertake measures to publicly share in-formation on prices and reimbursement cost of medicines, vaccines, cell and gene-based therapies and other health tech-nologies.”

According to the updated resolution, published by Health Policy Watch, which reports on global health issues, member states should also demand annual reports on sales revenues, pricing and units sold. This should be a condition of registration for medicines, vaccines, cell and gene

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Novel Procurement Deal To Rid England Of Hepatitis CFRANCESCA BRUCE [email protected]

A s part of a “ground-breaking” pro-curement deal between National Health Service England and Gilead Sciences Inc., AbbVie Inc. and Merck & Co. Inc., the three drug companies will provide their hepatitis C treatments and help find as yet diagnosed hepatitis C patients.

The deal is part of NHS England’s am-bitious plan to eliminate hepatitis C in England by 2025, five years earlier than the goal of 2030 set by the World Health Organization.

The deal, announced this week by NHS England, followed extensive negotia-tions and a court case. NHS England says it provides all five new hepatitis C drugs “at the best price for NHS and tax payers,” although details of what those prices are have not been disclosed. According to MSD, the agreement is the fruit of a new procurement approach undertaken by NHS England that “maximizes competition between drug companies to secure the best possible deal.”

As part of the deal, the three companies will work with local health services, coun-cils and voluntary groups to find poten-tially undiagnosed patients and test them.

GROUND-BREAKINGNHS England announced its plan with the hepatitis C elimination target of 2025 in January 2018. It described the agreement with the three drug companies as ground-breaking and first-of-a-kind. “The NHS’s sophisticated and unashamedly rigorous negotiation on behalf of both patients and taxpayers means we’ve now been able

to strike affordable deals with our life sci-ences partners to save many more lives and meaningfully cut health inequalities,” said Simon Stevens, chief executive of NHS England.

“It is definitely an innovative and unique procurement approach,” Gilead told the Pink Sheet. The approach has brought to-gether the NHS, industry and third sector stakeholders to eradicate a disease, it said. “Gilead has had agreements with govern-ments to work towards elimination in many countries across the world but this approach is innovative in that it has explic-itly required industry to work in partner-ship with the NHS and other stakeholders to help eliminate this disease.”

Gilead added that the process was con-structive and that there was “a real dialogue between the industry and NHS England.” The company welcomed the collaboration and said that bringing ground-breaking treatments to the UK required “more dia-logue and flexibility on both sides.”

Gilead pointed to its existing partner-ship with the NHS and Change Grow Live, a charity that provides health and social care support, as an example of the type of initiative that might come about. Through the partnership, Change Grow Live iden-tifies service users who have hepatitis C

therapies and other relevant technologies, it says. The resolution also calls for member states to demand annual reports on the marketing costs for each registered prod-uct; R&D costs for each clinical trial that sup-ports the registration and any grants, tax credits or other public sector subsidies and incentives relating to regulatory approval.

Meanwhile, the WHO director general is urged to create a web-based tool for na-tional governments that would allow them to share information, including medicines prices, revenues and R&D costs, and public sector investments.

The resolution also says the WHO should

create a forum through which experts and industry representatives, payers, patients, NGOs and charities can develop alterna-tive incentives to patent monopolies to re-ward innovation and help health authori-ties attain universal health coverage.

The WHO is also urged to create “a bien-nial forum on the transparency of markets for medicines, vaccines and diagnostics, to evaluate progress toward the progressive expansion of transparency.”

The resolution is backed by Greece, Ma-laysia, Portugal, Serbia, Slovenia, South Af-rica, Spain, Turkey and Uganda.

The 72nd WHA is scheduled to take place

in Geneva, Switzerland on 20-28 May. It will follow the Fairer Pricing Forum that was co-hosted by the WHO and the South African government in Johannesburg last month. According to the WHO, at the forum “there was consensus that countries can take an initial step towards fostering greater trans-parency by sharing price information.”

The WHO says that it will soon launch a public online consultation “to collect views and suggestions for a definition of what actually constitutes a ‘fair price’ from rel-evant stakeholders.”

Published online 2 May 2019.




using dried blood spot testing and also works with specialist NHS services to pro-vide treatment.

Meanwhile, MSD told the Pink Sheet that “the NHS has led a first-of-its-kind process to combine the way it uses medicines with a range of innovative industry-led servic-es,” It added that it “has been pleased to

be part of that process and delighted to be part of its successful outcome.”

According to MSD, the precise scope of the specific service that the compa-ny will provide is yet to be decided as part of ongoing talks with NHS England. However, it added that it has proposed a range of services. These include pri-mary care informatic solutions, innova-tive testing methods targeted to key groups and patient support provided by people who have had the virus and experienced treatment.

Companies in this procurement were given gold, silver or bronze status de-pending on “the size of market share the

companies have been awarded through the procurement,” explained the NHS.

Gilead came away with gold status. “Gold was awarded to the company that provided the best value to the NHS both in terms of the price of their products as well as commitment and proven ability to support patient finding. As such we are de-

lighted that Gilead’s overall submission has been recognized by NHSE and that we will play a leading role in working together to deliver the NHS England ambition of elimi-nating HCV,” said the company.

COURT CASENHS England’s announcement of the deal was held up by six months because of legal action brought by AbbVie, which claimed that certain aspects of the rules governing procurement were unfair and were a breach of the duty of equal treat-ment. In January the High Court dis-missed the claims.

AbbVie welcomed the announcement

of the deal. “We have worked closely with NHS England to build an HCV elimination strategy and we appreciate that the NHSE tender model will ensure availability of all suitable treatments in England,” said Joette Gdovin, head of UK market access.

Some 113,000 people are thought to have hepatitis C in England. But because the virus lacks symptoms in its earlier phases, combined with suboptimal test-ing and low-awareness, some 69% of those with a current infection are not diagnosed, according to the hepatitis C trust. As such, the trust has welcomed this part of the deal. “The funding in the deal to help find those with hepatitis C and support them into treatment is ground-breaking,” said the trust’s chief executive, Rachel Halford.

More than 30,000 patients have so far been treated by the new curative drugs that have been made available on the NHS over the last few years. According to NHS England, these new treatments have led to a 16% fall in the rate of deaths from hepa-titis C -related liver diseases between 2015 and 2017. In addition, a 40% reduction in liver transplants over the same period has led to cost savings.

Published online 2 May 2019.

“ This approach has explicitly required industry to work in partnership with the NHS and other stakeholders to help eliminate this disease.” - Gilead

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Pulmonary-Allergy Drugs May 8

Daiichi Sankyo’s pexidartinib for adults with symptomatic tenosynovial giant cell tumor Oncologic Drugs May 14

Daiichi Sankyo’s quizartinib for adults with relapsed/refractory acute myeloid leukemia, which is FLT3-ITD positive as detected by an FDA-approved test

Oncologic Drugs May 14

Global Alliance for TB Drug Development’s pretomanid as part of a combination regimen with bedaquiline and linezolid in adults for treatment of pulmonary extensively drug resistant and treatment-intolerant or non-responsive multidrug-resistant tuberculosis

Antimicrobial Drugs June 6

Clinical utility and safety concerns with the higher range of opioid analgesic dosing (higher strength products and higher daily doses) in the outpatient setting

Drug Safety and Risk Management/Anesthetic and Analgesic Drug Products

June 11-12

Review and discussion of two target classes in the Relevant Pediatric Molecular Target List: targets linked to cell lineage, and targets on normal immune cells and cells in the tumor microenvironment

Oncologic Drugs Pediatric Subcommittee

June 20

Potential pediatric development plans for Oncoceutics Inc.’s ONC201 and OncoImmune Inc.’s CD24FcOncologic Drugs Pediatric Subcommittee

June 20

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