September 1, 2012 (Vol. 32, No. 15)

Supreme Court Decision Left BPCI Intact, Clearing Pathway for FDA Final Ruling

Following the U.S. Supreme Court’s decision to leave intact the Patent Protection and Affordable Care Act, the development of biosimilars to treat a wide variety of diseases and health conditions is poised to surge. The Act contains important provisions that create a pathway for the FDA to approve “biosimilar” versions of previously approved biotechnology drugs.

The Act created an abbreviated licensure pathway for biological products in the part of the law known as the Biologics Price Competition and Innovation Act. Under the BPCI Act, a biological product may be demonstrated to be “biosimilar” if data shows that, among other things, the product is “highly similar” to an already approved biological product.

Anthony J. Fitzpatrick

The U.S. Supreme Court, in upholding the legislation, also removed the uncertainty over the immediate future of biosimilars. Now, biotech and pharmaceutical companies will likely quicken an already accelerating pace of partnership agreements, mergers and acquisitions, and technology deals to enable the production of biosimilars. The stakes are high:

  • Biologics are forecast to account for 7 out of 10 of the top prescription drugs by 2014.
  • Biosimilars are expected to cost 20–25% less than originator products due to reduced clinical trials and result in more patients having access to treatment.
  • The market for biologics is growing at a rate of two to three times faster than that for oral solid pharmaceutical products.
  • An estimated $63 billion of global biological sales products are due to come off patent by 2016—making partnerships with pharmaceutical companies an attractive continued revenue stream for reference drug developers.
  • The global biosimilar market is forecast to grow from $243 million in 2010 to almost $4 billion by 2017.
  • Several strategic partnerships between biotech companies and generics manufacturers are in place and clinical trials are under way, with several major deals announced since December 2011:
  • In January 2012, Sandoz initiated two Phase III trials for biosimilar versions of two Amgen biologics. One trial is for filgrastim, a biosimilar of Amgen’s Neupogen, and the other is for its global pegfilgrastim development program, a biosimilar of Amgen’s Neulasta. The filgrastim study is evaluating Sandoz’ biosimilar filgrastim versus Neupogen in breast cancer patients eligible for myelosuppressive chemotherapy treatment. Likewise, the pegfilgrastim study is being conducted in breast cancer patients undergoing myelosuppressive chemotherapy treatment. Filgrastim is already marketed under the brand name Zarzio in more than 30 countries.
  • Hospira began Phase III trials in January to compare the safety and efficacy of its biosimilar erythropoietin (EPO) and the reference product, Amgen’s Epogen, in patients with renal dysfunction who have anemia. Erythropoietin is a treatment for anemia associated with chronic renal failure. Hospira’s program will enroll approximately 1,000 patients on hemodialysis who have already been treated with Epogen. Results are scheduled for 2013. Hospira already sells a biosimilar EPO in Europe: Retacrit.
  • Amgen and Watson Pharmaceuticals reached an agreement in December 2011 to develop and market biosimilar treatments for cancer, with Amgen developing and manufacturing the biogenerics and Watson providing marketing and financial support.
  • Baxter International and Momenta Pharmaceuticals entered into a global collaboration in December 2011 to develop and commercialize up to six follow-on biologic compounds.
  • Samsung and Biogen Idec announced in December 2011 that they have entered into an agreement to establish a JV to develop, manufacture, and market biosimilars.
  • Additional companies that market biosimilars abroad are conducting trials in the U.S. Biosimilars were first approved in Europe in 2006 and companies with facilities in the EU have gained technical and regulatory experience there that can give them an advantage in the U.S.

Vincent L. Capuano, Ph.D.

The battleground over biosimilars is expected to move next to the scope of clinical trials required by the FDA—which promises to be a hotly contested issue. Biologic License Application (BLA) holders will contend that certain studies are required to maintain safety while biosimilar applicants will argue that extensive studies are not needed since those studies have already been conducted for the original product, and that the differences between the biosimilar product and the reference product are sufficient to establish clinical similarity, without repeating the clinical studies carried out with the reference product.

The industry is waiting for final rulemaking from FDA, and biosimilar applications are expected to be filed with the FDA shortly thereafter.

In February 2012, the FDA issued three draft guidance documents on biosimilar product development regarding key scientific and regulatory factors involved in submitting applications for biosimilar products to the agency:

Scientific Considerations in Demonstrating Biosimilarity to a Reference Product:

The draft guidance is intended to assist companies in demonstrating that a proposed therapeutic protein product is biosimilar to a reference product for the purpose of submitting a 351(k) application to the FDA. This draft guidance describes a risk-based “totality-of-the-evidence” approach that the FDA intends to use to evaluate the data and information submitted in support of a determination of biosimilarity of the proposed product to the reference product.

Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product:

This guidance provides an overview of analytical factors to consider when assessing biosimilarity between a proposed therapeutic protein product and a reference product for the purpose of submitting a 351(k) application. This includes the importance of extensive analytical, physicochemical, and biological characterization in demonstrating that the proposed biosimilar product is highly similar to the reference product notwithstanding minor differences in clinically inactive components.

Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009:

The draft provides answers to common questions from companies interested in developing biosimilar products. The question and answer format addresses questions that may arise in the early stages of product development, such as how to request meetings with the FDA, addressing differences in formulation from the reference product, how to request exclusivity, and other topics.

The FDA provided a 60-day period for stakeholders to offer comments. The comment period has ended and the FDA will issue final regulations, respond to comments, or both, later this year, probably in the third quarter.

The FDA received submissions from an array of stakeholders, including the Biotechnology Industry Organization (BIO). BIO has advocated that the FDA expand the requirements to prove biosimilarity significantly beyond the minimum tests mandatory in the statute, and generally recommends policies that make it more difficult to obtain expedited approval created under the BPCI Act.

Congressional intervention is unlikely at this stage. The Supreme Court’s upholding of the BPCI Act as part of the Affordable Care Act now clears the way for final FDA rulemaking and the beginning of a new era of U.S. healthcare that will include affordable biosimilar medicines.

Vincent L. Capuano, Ph.D. ([email protected]), and Anthony J. Fitzpatrick are partners at Duane Morris

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