Category: FDA

In 2015, FDA issued a number of final guidance documents for biosimilars but many fundamental questions remain unsettled, including the requirements for labeling of biosimilars, interchangeability, and naming.   There is much ahead for the US biosimilars pathway in 2016.

On January 26, 2016, the World Health Organization (WHO) unveiled the final version of its proposal for a worldwide biosimilar naming convention. The WHO proposes to add a “biologic qualifier” (BQ), which consists of four random consonants and an optional two-digit checksum, as an identifier that follows the nonproprietary name of each biologic and biosimilar product. This proposal resembles FDA’s biosimilar naming proposal, which adds four random consonants as a suffix to nonproprietary names. Industry and healthcare stakeholders have criticized FDA’s proposal to use random suffixes, instead of meaningful—and therefore memorable—ones, due to a greater likelihood of reporting and prescription errors with meaningless names. The WHO proposal, which uses a randomly generated separate identifier, is likely to draw similar criticism.

On November 19, 2015, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion, recommending marketing authorization of Samsung Bioepis’s Benepali, the first biosimilar of Enbrel (etanercept), in Europe.  Enbrel is a blockbuster treatment for rheumatoid arthritis and a number of other autoimmune conditions associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), a protein that plays an important role in promoting inflammation.  The CHMP recommended approval of Benepali for these conditions.  In the US, FDA recently accepted Sandoz’s regulatory application for its proposed biosimilar of Enbrel for review.  Sandoz is seeking approval for all of Enbrel’s indications.  FDA’s review of Sandoz’s proposed biosimilar will provide important information on the requirements for biosimilarity and extrapolation for complex biologic products.

In its draft guidance, FDA proposed distinguishable nonproprietary names for biosimilars to promote the safety of patients receiving biologic medicines and minimize inadvertent substitution of biologics that have not been determined to be interchangeable.  FDA did not make a proposal for naming interchangeable biological products.  Instead, FDA requested comments on how to name such products in addition to seeking comments on its approach to naming biosimilars.  Stakeholders’ comments are now in.  Innovator companies (including those that also develop biosimilars), healthcare providers and patient advocacy groups favor distinguishable nonproprietary names for biosimilars.  Biosimilar makers, insurers, pharmacies, and the FTC, by contrast, largely fall into a different camp; they argue that distinct names are unnecessary for monitoring biosimilars and will likely bias providers against prescribing them.  Notably, the two camps came together on the naming of interchangeable products.  Since interchangeable products will likely first be approved as biosimilars, both camps advocated keeping the initial biosimilar name rather than changing it after approval as an interchangeable product.  As a result of this unified view, FDA is likely to expand the naming approach it ultimately adopts for biosimilars to interchangeable products.  

The first biosimilar makers to file regulatory applications with FDA attempted to bypass all or a subset of the patent litigation provisions of the Biologics Price Competition and Innovation Act of 2009 (BPCIA). Apotex, the third biosimilar maker to file an application for approval of a biosimilar product with FDA, chose a different course. Apotex participated in and completed the BPCIA’s pre-suit information exchanges (also known as the “patent dance”) for its proposed biosimilar of Amgen’s Neulasta (pegfilgrastim). As Amgen’s recent lawsuit shows, Apotex followed the patent dance again for its proposed biosimilar of Amgen’s Neupogen (filgrastim).    

The FDA approved label for the first U.S. biosimilar, Sandoz’s Zarxio, has raised concerns.  Zarxio was launched on September 3, 2015 with a label that does not state that the product was approved as a biosimilar to Amgen’s Neupogen and that it has not been determined to be interchangeable to Neupogen.  Instead, Zarxio’s label is nearly identical to that of Amgen’s Neupogen and does not identify the information provided by Sandoz to FDA to obtain Zarxio’s approval, including information on immunogenicity specific to Zarxio. AbbVie has supplemented its citizen petition urging FDA not to allow biosimilars to be labeled like generic drugs since biosimilars, unlike generic drugs, are not identical to the originator product and requesting distinct labeling for biosimilars.  In briefing U.S. senators on September 17, FDA promised to issue guidance on labeling of biosimilars.  

The FDA has issued a long-awaited draft guidance document and proposed rule on the nonproprietary names for biosimilar medicines.  FDA proposes to give biosimilars a “core name” shared with all related biological products and a four-letter suffix, unique to each product.  The four-letter suffix, unlike the placeholder name for the first US biosimilar, Sandoz’s Zarxio (filgrastim-sndz), does not identify the product’s manufacturer.  Instead, it is a random collection of four letters, “devoid of meaning.”  Patient groups and physicians have applauded FDA’s use of unique suffixes to differentiate biological products but innovator companies prefer meaningful suffixes, such as the one for Zarxio, and biosimilar manufacturers argue for no distinguishing names at all.  

A number of biosimilar makers have turned  to inter partes review (IPR) proceedings to challenge innovator patents prior to submitting their biosimilar applications to FDA.  IPRs have been attractive to biosimilar makers because in addition to offering procedural and substantive advantages for challenging patents they do not require the filing of a biosimilar application.  As a result, they make it possible for biosimilar makers to obtain patent certainty at a time when litigation under the Biologics Price Competition and Innovation Act of 2009 (BPCIA) is premature and, depending on the results of the IPRs, may be avoided entirely.  The first such IPRs, however, are yielding mixed results, leaving potential patent disputes for later BPCIA litigation.  

The BPCIA created an abbreviated pathway for FDA approval of biological medicinal products that are “biosimilar” to an already FDA-approved product.  The FDA recently approved the first U.S. biosimilar – Sandoz’s biosimilar of Amgen’s Neupogen – and is currently reviewing at least four other proposed biosimilars.  Many innovators and biosimilars manufacturers are responding to the changing landscape for biologics by developing “biobetters”:  new and improved versions of biologic medicinal products.  While biobetters require discovery and an original Biologics License Application (BLA) with a full complement of pre-clinical and clinical data for marketing approval, they also offer many advantages.  By offering superior and longer-acting medicine, biobetters provide a competitive advantage over biosimilar products.  In addition, unlike biosimilars, they generally would be entitled to patent protection and 12 years of non-patent exclusivity under the BPCIA.  

On May 13, the FDA released additional draft question-and-answer guidance on the implementation of the BPCIA.  The draft document resurrects a number of the questions from FDA’s original 2012 draft guidance that were omitted from last month’s final version of the 2012 document.  As a result, FDA’s final answers to important questions from three years ago may not be forthcoming for some time. 

On March 6, the Food and Drug Administration (FDA) approved the first biosimilar in U.S. history—Sandoz’s biosimilar of Amgen’s blockbuster drug used to prevent infections in cancer patients, Neupogen. Sandoz, a Novartis company, reaped tremendous savings in cost and time by taking advantage of the new biosimilar pathway rather than submitting a full biologics license application (BLA) to the FDA and undertaking all the studies that Amgen had to perform to obtain approval for Neupogen. The extent to which these savings will be passed on to the U.S. health care system as envisioned by the Obama administration, however, is less clear.

Zarxio is the first biosimilar approved under the 351(k) pathway, but it is not the first “biosimilar” to be approved in the U.S.  For a small category of follow-on biologics, there is another pathway for marketing approval -- and it is only available for the next five years.

The exclusivity period for biologic drugs has recently become a hot topic in both domestic and foreign policy. At home, the Obama administration’s latest budget proposes reducing the exclusivity period to seven years, down from its current 12. Abroad, the exclusivity period for biologics has developed into a sticking point in negotiations over the Trans-Pacific Partnership.

Welcome to the Biologics Blog, which will track and analyze developments in intellectual property law related to biologic medical products as well as regulatory and legislative changes. Our impetus for starting the blog is the recent onset of regulatory activity and litigation under the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), which created a new regulatory and legal framework for biosimilar and interchangeable biologic products.