Articles Posted in Biologics

leerink.pngOn February 12 and 13, 2014, Leerink Partners LLC (“Leerink”) held its annual Global Healthcare Conference at the Waldorf-Astoria Hotel in New York, New York. Each year the Conference includes emerging themes in healthcare, where Leerink’s equity analysts moderate discussions with MEDACorp specialists to provide unique and timely insights.

In addition to the company presentations, this year’s line up featured the following panels or keynote speakers with some observed comments or trends:

• Panel: The Future of Medical Devices in an Evolving Landscape: A Shifting Emphasis to Patient Monitoring and Customizable Solutions

  • Patients view surgeons that incorporate robotics in their practice as the better doctors, driving more surgeons to utilize them in their practice. As surgeons become more familiar with these devices, patients may have more options for surgical procedures and implants.
  • Larger companies are looking at controlling infections caused by implanted medical devices with special coatings–either anti-infectives or antibiotics, particularly for use in higher-risk patients. There is an increasing need, however, for implants to have built-in tools for monitoring the devices. But as medical devices become more complex, such as hip, knee, or total joint replacements, these devices will require preapproval marketing applications (“PMAs”) with clinical data rather than less costly and time-consuming 510(k)-type premarket clearance applications. Since PMAs cost companies more than 510(k) applications, these newer devices will cost third party payors and patients more.
  • Hospitals continue to be under a lot of pressure not to lose patients, so they may seek lower margins by having surgeons add anti-infective coatings or antibiotics rather than purchasing more costly versions with the coatings or by importing “generic” implants from other countries that may not be as rugged as the versions cleared for use in the U.S. FDA’s new unique device identifiers and improved monitoring, however, may reduce use of such imported devices with unclear pedigrees.

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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 www.biocenturytv.com 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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genetherapy.jpgOn February 25-26, 2014, FDA will hold a meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee. A majority of the meeting will concern oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease or treatment of infertility. While FDA will post meeting materials at least two business days before the meeting, one item that will likely be discussed is a workshop held in September 2002 on Evidence Based Assisted Reproductive Technologies (ART) that concerned oocyte modification. Approximately half of the second day will focus on considerations for the design of early-phase clinical trials of cellular and gene therapy products, which was the topic of a revised guidance published on July 2, 2013. This meeting was originally scheduled for October 22-23, 2013 but was postponed “due to resource constraints arising from the government shutdown.”

The July Draft Guidance provided recommendations to assist in designing early-phase clinical trials of cellular therapy (“CT”) and gene therapy (“GT”) products, collectively referred to as “CGT products”, which covers most Phase 1 trials and some Phase 2 trials. FDA considers clinical study designs for CGT products to be different because of the way the products work and the potential for substantial risk. In the past, FDA halted CGT therapies due to experiences that included: (1) multiple-organ failure and death of a subject receiving a GT product for ornithine transcarbamylase deficiency, (2) late-onset T-cell leukemia in subjects who received a GT product for X-linked severe combined immunodeficiency, and (3) the development of tumors in the brain and spinal cord of a patient who received intrathecal allogenic stem cells for ataxia telangiectasia.

FDA’s Guidance on early-phase clinical trials explained that unlike many small molecule drugs, there is much less experience across a broad population with CGT products, leading to more uncertainty with clinical study design and controls. Some CGT products persists in humans for an extended time period and the administration may involve surgery or other invasive procedures that may require use of an investigational medical device. Allogenic CT products, GT vectors, and proteins that may be produced by CGT products have the potential to produce an immune response that may produce an unintended adverse reaction or sensitivity to a CGT product in the future. CGT products are cellular products and so mimic the complex, dynamic nature of living cells, which can migrate within the recipient’s body.
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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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transfat.jpgFDA has tentatively found that partially hydrogenated oils (“PHOs”), the primary dietary source of trans fatty acids, are no longer generally regarded as safe (“GRAS”). While PHOs are used in a number of food products (e.g. margarine, shortening, and baked goods), they have been linked to significant health risks, such as coronary heart disease. FDA’s tentative determination that PHOs are no longer GRAS means that PHOs would now be classified as “food additives,” subject to Section 409 of the Federal Food, Drug, and Cosmetic Act (“FD&C Act”) (21 U.S.C. 348). FDA does not allow food manufacturers to sell food additives, directly or indirectly, without prior approval for us by FDA.

The FD&C Act defines a “food additive” as “any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food….” 21 U.S.C. 321(s). Except that GRAS substances are not considered food additives. A substance is GRAS if it is generally recognized to be safe under the conditions of its proposed use “among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures.” In addition, if the substance had been used in food before January 1, 1958, it could be considered GRAS based on experience form its “common use” in food. However, even common use in food cannot overcome new evidence demonstrating that a consensus no longer exists that the substance is safe.

While some GRAS substances are listed in the regulations, there is no comprehensive list of GRAS substances. With the passage of the Food Additives Amendment to the FD&C Act in 1958, FDA established a list of GRAS substances. And in 1972, FDA instituted a notice-and-rulemaking procedure for affirming certain substances as GRAS. However, in 1997, FDA instituted a voluntary notification program for GRAS substances, which does not require notice-and-comment rulemaking. Thus, in many cases, food manufacturers and users have been responsible for determining whether substances are GRAS in light of the views of experts. For example, partially hydrogenated soybean oil and partially hydrogenated cottonseed oil were considered GRAS based on common use prior to 1958, but are not listed as GRAS in any FDA regulation.
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biotechgiant.jpgOn October 3, 2013, the Tech Council of Maryland (“Tech Council”) hosted a Bioscience Series presentation “Industry Giants” in Bethesda, Maryland. The Tech Council’s is Maryland’s largest trade association for bioscience and technology companies employing more than 200,000 in the region. The Industry Giants event was kicked off by the Tech Council’s new Chief Executive Officer, Philip Schiff, formerly chief strategy officer of the American Association of Blood Banks (“AABB”) (also known as “Advancing Transfusion and Cellular Therapies Worldwide”, which is a not-for-profit trade association based in Bethesda, Maryland, that that advances the practice and standards of transfusion medicine and cellular therapies to optimize patient and donor care and safety.)

The Industry Giants panel was moderated by Ray Briscuso, Annual Conference Chief Executive AdvaMed, former Executive Director, Biotechnology Industry Organization (“BIO”), and featured speakers: Steven Dubin, former Chief Executive Officer of Martek Biosciences (“Martek”); Charles Fleischman, former President, Chief Operating Officer and Chief Financial Officer of Digene Corporation (“Digene”) (now Qiagen), and Tom Watkins, former Chief Executive of Human Genome Sciences (“HGS”). All three former executive speakers came from companies that were acquired for over a billion dollars yet have managed to maintain their ties to the life sciences field.

Dubin’s Martek focused on a microbial platform with a unique technology for nutrition and functional ingredients. Dubin recounted how it took a long time for the company to become profitable (18+years), which he thought would be a hard model to follow in today’s times, particularly since they went public at least 6-7 years before there was a profit. Dubin thought that he learned by getting involved in the biotech community and by bringing in people who he thought were smarter than he was to help build passion in the company culture, which he found critical. He thought that emerging biotechnology companies should not focus so much on the exit strategy and found going public a “huge distraction” for the company to continuously answer to its investors. When asked what he respected from individuals looking to provide services for his company, he said that he thought it was important to first build a relationship and understand the company’s problems before asking for work.
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