Articles Posted in Biosimilars

On Sunday, February 16, BioCentury This Week television examined the policies surrounding the expected competition of innovator biologic products with biosimilar versions. Featured in the program were interviews with:

  • Geoffrey Eich, Executive Director of R&D Policy at Amgen Inc.
  • Craig Wheeler, President & CEO of Momenta Pharmaceuticals Inc.
  • Brian Malkin Partner at Frommer Lawrence & Haug LLP and former Regulatory Counsel in the Office of the FDA Commissioner and the Center for Drug Evaluation and Research

Links to the interviews may be found below:


Brian Malkin

BioCentury 02/16/14 Safety v. Competition


Geoffrey Eich

BioCentury 02/16/14 Brand-Name Confidence


Craig Wheeler

BioCentury 02/16/14 Substitution Confusion

BioCentury 02/16/14 Competing Interests


BioCentury This Week.pngSunday, February 16: The Battle Over Biosimilar Business Models.

Biosimilars — lower-cost versions of expensive biologics — are coming to pharmacy shelves in the U.S. But biosimilars players disagree about how they should compete.

Should biosimilars be sold like inexpensive generic drugs? Or should they be sold at higher prices like branded drugs?

On Sunday, February 16, BioCentury This Week television examines the policies the two sides are fighting over with:

  • Geoffrey Eich, Executive Director of R&D Policy at Amgen Inc.
  • Craig Wheeler, President & CEO of Momenta Pharmaceuticals Inc.
  • Brian Malkin, Partner at Frommer Lawrence & Haug LLP and former Regulatory Counsel in the Office of the FDA Commissioner and the Center for Drug Evaluation and Research

Key opinion leaders; sophisticated questions Always on BioCentury This Week television
Watch the Broadcast 8:30 – 9:00 a.m. EST WUSA Channel 9 in Washington, D.C.

Watch on the Web Continuously available starting at 9:00 a.m. EST
Get BioCentury This Week alerts on your mobile phone every week text “BIO” to 25543 (standard text messaging rates apply).

DNApurple.jpgOn February 4, 2014, the U.S. Federal Trade Commission (“FTC”) held a Workshop entitled: “Follow-On Biologics Workshop: Impact of Recent Legislative and Regulatory Naming Proposals on Competition“. The Workshop was well attended and sought to solicit a variety of views on the marketing of follow-on biologics, currently referred to as “biosimilars” under the Biologics Price Competition and Innovation Act (“BPCIA”).

Briefly, the BPCIA defines “biosimilarity” as “[T]he biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components” and “there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.” A biosimilar is submitted as a 351(k) application, which must contain, among other things, information demonstrating that the biological product is biosimilar to a reference product based upon data derived from analytical studies, animal studies, and a clinical study or studies, unless FDA determines, in its discretion, that certain studies are unnecessary. To meet a higher standard of “interchangeability,” an applicant must provide sufficient information to demonstrate biosimilarity, and also to demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient and, if the biological product is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch. According to the BPCIA, interchangeable biosimilar products may be substituted for the reference product without the intervention of the prescribing healthcare provider.

As explained by Edith Ramirez, FTC Commissioner, many state legislatures have either passed or are considering legislation to explain how to handle biosimilars that are not interchangeable (and sometimes including interchangeable biosimilars), which may affect competition for the market at this juncture before even one biosimilar has been approved. In particular, many of the state laws or bills include provisions for prescriber notification of possible biosimilar substitution for the referenced innovator biologic product. FDA and other regulatory bodies are still considering universal nomenclature for biosimilars, which may either create the same or similar names for biosimilars and their referenced innovator biologic products. The FTC sees similarities between biosimilars and how generics were first perceived and opportunities to either facilitate or hinder acceptance of biosimilars in the market that they wanted to explore in this Workshop.
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Jnj.jpgJohnson and Johnson (“J&J”) recently joined the discordant chorus of stakeholders and commentators who have weighed in on the issue of naming for biosimilar products. On the one hand, some advocate for shared International Non-Proprietary Naming (“INN”) system names between a biologic approved under Section 351(k) of the Biologics Price Competition and Innovation Act of 2010 (“BPCIA”) and the reference protein product (“RPP”). Conversely, others argue that biosimilars and RPPs should be assigned unique INNs. Whether biosimilar products are given the same or unique names matters: biosimilar products with unique names will likely require independent marketing and detailing (i.e., automatic substitution will not be available). For its part, J&J requests that FDA “require biosimilars to bear nonproprietary names that are similar to, but not the same as, those of their reference products or other biosimilars.”

J&J cites to its experience with Eprex®/Erypo® recombinant human erythropoietin (epoetin alfa), to inform its position on biosimilar naming. In particular, J&J identified four considerations that arose from its experience: (1) reliable pharmacovigilance mechanisms are necessary for postmarket safety; (2) products may undergo clinically-meaningful changes over time; (3) effective pharmacovigilance can only occur when it is possible to identify the product administered to a patient; and (4) switching products can interfere with determining which product is responsible for any given adverse effect. For example, J&J received reports of erythopoetin antibody-mediated pure red cell aplasia in Thailand between 2004-2007 but were unable to pinpoint the adverse event reports to a specific epoetin product due to incomplete documentation and frequent product switching.

Based on this experience, J&J argues that giving a biosimilar product the same name as the RPP would interfere with pharamacovigilance. For example, J&J states that, “to the extent that adverse event reports identify a product solely by nonproprietary name, shared names would complicate if not prevent tracing a safety signal to a specific product.” J&J also states that physicians may submit adverse event reports that incorrectly identify the responsible product if switching occurs without the knowledge of the physician.
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Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for dna.jpg[Update: The Workshop was cancelled on December 10, 2013, due to weather-related closure of the federal government. On December 30, 2013, FTC announced the Workshop would be held on February 4, 2014, at the FTC Conference Center at 601 New Jersey Avenue, NW, Washington, D.C. and will be webcast. FTC will publish an updated agenda and list of speakers. The comment period is unaffected by the rescheduling of the event, i.e., due by March 1, 2014.]

On December 10, 2013, the Federal Trade Commission (“FTC”) will host a Workshop on the Competitive Impacts of State Regulations and Naming Conventions Concerning Follow-on Biologics. FDA has yet to receive its first biosimilar application filed under the Biologics Price Competition and Innovation Act of 2010 (“BPCIA”). Despite this, the FTC believes that some state legislatures have already passed laws that may affect substitution of biosimilars for their referenced innovator biologic products. As a result, the FTC is concerned that these laws may deter the development of biosimilars and raise the costs for consumers without biosimilar options.

FTC’s Workshop plans to cover some of the following questions:

  • How would the new state follow-on biologic substitution laws passed this year, or similar proposals pending in other states, affect the competition expected between or among biosimilar, interchangeable and reference biologic medicines?
  • What are the rationales behind new state proposals and laws for regulating follow-on biologic substitution?

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dna.jpgYears have passed since enactment of the Biologics Price Competition and Innovation Act of 2009 (“BCPIA“), and we have been waiting for developments–from government, industry, and/or law–that would spark life into the biosimilars’ industry. But, with FDA taking a wait-and-see approach, industry unwilling to act without more FDA guidance, and the courts not having any cases to decide, progress on the biosimilars’ front has been slow.

Some of that may change though after a judicial decision coming out of the Northern District of California this week. There, Judge Maxine Chesney nixed Sandoz’s early challenge to two Hoffman-La Roche (“Roche”) patents covering etanercept, a human tumor necrosis factor receptor. Amgen, the exclusive licensee of the patents, claims they cover its Enbrel® product. Sandoz, who is currently conducting clinical trials to test an etanercept product, stated that once the trials were complete, it intended to file an application for licensure of its etanercept product as biosimilar to Enbrel®. Accordingly, Sandoz sought a declaration that its claimed biosimilar product did not infringe either patent, and that both patents were invalid and unenforceable.

Sandoz contended that declaratory relief was appropriate, because it had provided notice of commercial marketing. In opposition, Roche and Amgen made two related arguments: (1) the district court did not have standing to consider the patent dispute, because Sandoz had not yet submitted an application to FDA and (2) there was no cognizable case or controversy. The court agreed with Roche and Amgen, finding a number of problems with Sandoz’s position.
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Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for gpha-headerLogo.gifOn September 17, 2013, the Generic Pharmaceutical Association (“GPhA”) formally jumped into the biosimilars naming fray by recently submitting a Citizen Petition to FDA on the issue. GPhA’s Petition argues that a biologic approved under Section 351(k) of the Biologics Price Competition and Innovation Act of 2010 (“BPCIA”) should share the same International Non-Proprietary Naming (“INN”) system name as the reference protein product (“RPP”). GPhA’s position stands in sharp contrast to a position voiced by the Biotechnology Industry Organization (“BIO”) and Pharmaceutical Research and Manufacturers Association (“PhRMA”), which was outlined in a letter addressed to Margaret Hamburg last year. The BIO/PhRMA letter asserts that biosimilars are merely similar to–but not the same as–an RPP, and therefore each product should be assigned a unique INN. Requiring a unique INN will very likely require biosimilar applicants to market and detail biosimilar products themselves (instead of relying on the automatic substitution which occurs for generic small molecule drugs in most states).

The BPCIA does not provide a naming convention for biosimilar products. GPhA argues that FDA’s experience with biologic products that undergo post-approval manufacturing changes should serve as an exemplar for biosimilars. For example, GPhA argues that FDA applies “conceptually the same standard” to approving biologic manufacturing changes as the “highly similar” standard required by the BPCIA. And for biologic manufacturing changes, FDA allows the RPP product to maintain the same INN as prior to the manufacturing change. Thus, GPhA argues that FDA should apply its naming standard for manufacturing changes to biosimilars as well. If FDA determines that biosimilars require different INN names than the RPP, then GPhA argues that FDA will be forced to require “new INNs for any product, originator or biosimilar, which undergoes a manufacturing change using comparability.”

GPhA also addressed concerns that shared RPP and biosimilar INNs would interfere with product tracking. GPhA counters that notwithstanding a shared INN, biosimilar product labeling will contain sufficient information for tracking, such as manufacturer name, brand name, lot number, and NDC code. What is more, the results of a survey commissioned by GPhA reveal that “[h]ealth professionals typically report multiple elements whenever possible and include only the INN as the sole data point less than 30% of the time.” On the other hand, GPhA argued that requiring a unique INN for each biosimilar could jeopardize patient safety by resulting in: (1) prescribing errors by clinicians, such as the possibility of double-dosing, (2) untreated patients due to compromised access, and (3) a failure to pick up safety issues that would only be apparent in aggregated data.
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Obamabudget.jpgOver the past months, there has been a lot of speculation (see recent blogs here , here, and here) whether the White House’s proposed budget would cause a sequester situation for FDA, resulting in potential layoffs or program cuts, in an era of new user fees for generic drugs and biosimilar biological products. While initial reports and temporary budget fixes (called continuing resolutions) appeared to keep FDA’s user fees intact and available for use, FDA’s Commissioner, Margaret A. Hamburg, M.D., recently reported to members of a biotechnology trade association, the Massachusetts Biotechnology Council (“MassBio”), that it was not clear what would happen with user fees in the new federal budget.

Released on April 10, the White House’s proposed fiscal year 2014 budget is a mixed bag that has been called a “political document rather than a serious piece of legislation” with a “series of bargaining positions” that “would bleed pharma.” On the one hand, the plan would appear to confirm that FDA’s user fees would not be sequestered, given that it supported the $4.7 billion in total program budget requested by FDA, which included user fees that would help fund over 90 percent of the requested increases. On the other hand, the budget includes a myriad of proposals that would change the way the government pays for medical care and products. For example, Medicare (senior citizens’ drug coverage) Part D manufacturer discounts for branded drugs would be increased from 50% to 75% in 2015 (rather than 2020) and low-income individuals would be pushed more to generic drugs by increasing certain copayments for branded drugs and lowering certain copayments for generic drugs.

Many of the more controversial proposals were nestled in a document called “Reducing the Deficit in a Smart and Balanced Way”. Here, the White House proposes, among other things, several items to purportedly lower drug costs, including: 1) authorizing the Federal Trade Commission to stop companies from entering into certain “pay-for-delay” agreements (see below) and 2) beginning in 2014, to reduce biologic product exclusivity from 12 years to 7 years and prohibit additional periods of exclusivity for minor changes to product formulations. These two items could open up some unanticipated debate regarding the White House’s budget.
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dna.jpgOn April 1, FDA issued a Federal Register Notice announcing a new draft biosimilars guidance, “Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants“. This is the latest in FDA’s new biosimilar guidances for 2013, which FDA has announced in earlier meetings this year would be coming to help spur the filing of a biosimilars application, which FDA has called 351(k) applications based on the section in the Public Health Service Act (“PHS Act”). As of a few weeks ago at the Massachusetts Biotechnology Association’s (“MassBio’s”) Annual Meeting, which we blogged on here, FDA’s Commissioner, Margaret A. Hamburg, M.D., continued to report that FDA has not received a single 351(k) application to date.

The Guidance focuses on formal meetings for 351(k) applications and the associated requirements or performance goals from the Biosimilar User Fee Act of 2012 (“BsUFA”), which was enacted as part of the Food and Drug Administration Safety and Innovation Act (“FDASIA”). In particular, the Guidance discusses the principles of good meeting management practices (“GMMPs”) and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings.
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monoclonal antibodies.pngOn March 14-15, the Massachusetts Biotechnology Council (“MassBio”) held its Annual Meeting in Cambridge, Massachusetts. The Meeting also featured a Keynote from FDA Commissioner Margaret A. Hamburg, M.D. (see related blog here). Key themes at the Meeting were the importance of the Cambridge/Boston biotechnology community for advancing new therapies and the unique resources available in the area that have made it an industry leader. Some of the Cambridge/Boston advantages discussed were the intellectual research capital (local universities such as Harvard and Massachusetts Institute of Technology), venture capital, and local biotechnology businesses, such as Biogen Idec and Genzyme, as well as other biotechnology companies that now have offices in the Cambridge/Boston area and are seeking partnerships to develop new products, such as AstraZeneca, Pfizer, Merck, Novo Nordisk, and Sanofi.

On the second day, Hamburg described here “special affection” for the Cambridge/Boston region dating back to her days at Harvard, saying that she hopes D.C. “would be as efficient and congenial as here.” Hamburg said that the Cambridge/Boston region is a life sciences enterprise fueled by top notch research and medical care with the top five NIH-funded hospitals and a “biotech supercluster second to none” with “a remarkable 500 biotech and pharma companies here, and some thirty venture capital firms.”

Hamburg described FDA as striving for true collaboration and regulatory flexibility with industry, including MassBio, and has been hearing that industry wants more clarity, certainty, transparency with decisions. Hamburg said that FDA is trying to have creative approaches–not a one size-fits-all approach. To this end, Hamburg described approaches that FDA has taken with four new products from the Massachusetts area: 1) Inclusig® for two rare forms of leukemia, 2) Juxtapid® (an orphan drug), 3) Linzess® for irritable bowl syndrome, and 4) Kalydeco® for cystic fibrosis. In addition, Hamburg highlighted new provisions in the Food and Drug Administration Safety and Innovation Act (“FDASIA”) for expedited approvals, citing 31 breakthrough therapy designation requests, of which 9 have been granted, 10 denied, 11 pending, and 1 withdrawn. To help with more companies taking advantage of this new process, FDA will be publishing a new guidance shortly, Hamburg announced.
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