Prospects in Congress have improved this year for passage of landmark legislation that would allow the US Food and Drug Administration (FDA) to approve marketing of follow-on biologics or biosimilar drugs once patents had expired on pioneer biopharmaceuticals. With the introduction of this legislation in the House in March, combined with a comparable bill that passed a Senate committee last June, lawmakers appear closer to reaching bipartisan consensus on key elements of a regulatory pathway for approving biosimilar biological products.
But in a reversal of stereotyped roles, the generics biopharmaceutical industry opposes the current legislative thrust while the branded industry supports it. The “Pathway for Biosimilars Act” (HR 5629), introduced in March by Reps. Anna Eshoo (D-Calif.) and Joe Barton (R-Texas), key members of the House Energy and Commerce Committee, would create a framework for approving follow-on biological products, comparable in many ways to the Hatch-Waxman Act. This 1984 law essentially created the generic drug industry by allowing manufacturers to demonstrate bioequivalence to chemical drugs without supplying additional (and expensive) safety and efficacy data.
In exchange for creating a regulatory pathway for biopharmaceutical drugs, the House bill would give pioneer or innovator companies a base of 12 years (and up to 14.5 years in some cases) of market exclusivity before generics manufacturers would be permitted to compete. Because of this, the House measure “is a pathway to the wrong destination for patients in need of safe and affordable biogenerics,” said Kathleen Jaeger, president of the Generic Pharmaceutical Association (GPhA). She said granting an additional 14.5 years of market exclusivity “beyond the years companies already have under their existing patents” would be “unwarranted,” “unprecedented,” and “unjustifiable.”
But the Biotechnology Industry Organization (BIO), which is urging lawmakers to extend to the market exclusivity base for pioneer products to 14 years, nevertheless said that the exclusivity period should run concurrent with the drug’s patent term, not in addition to it. The generic drug industry, said BIO President Jim Greenwood, “keeps pushing misinformation to the news media, policymakers and others that is flat out wrong.”
While the back and forth makes for amusing political drama, the stakes are nothing to laugh at. Biopharmaceuticals—large molecules or complex proteins that are synthetic or recombinant versions of natural biological substances, such as human growth hormone, insulin, erythropoietin, and blood coagulation factors—represent 10% to 15% of the world’s pharmaceutical market. Sales of biological drugs in the US are expected to reach $50 billion by 2010.
But while patents on dozens of biologics having annual sales of between $10 billion to $15 billion have either expired or will do so over the next several years, no follow-on biotech drug has been approved in the United States. For unlike their small-molecule chemical counterparts, biological drugs are difficult to produce with consistency, even by the same manufacturer. And because biologics are derived from specific cell lines, manufacturers argue that generic versions cannot be truly identical.
Because of this, the House bill requires a biosimilar applicant to conduct analytical studies demonstrating the product is “highly similar” to the reference product; conduct animal studies; and also conduct at least one clinical study including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics. Both the House bill and last year’s Senate bill (S 1695), which has the support of such heavyweights as Sens. Edward Kennedy (D-Mass.), Hillary Rodham Clinton (D-N.Y.) and Orrin Hatch (R-Utah), give the FDA discretion to waive these studies. But the House bill, unlike the Senate version, requires FDA to have first issued guidance on data requirements for immunogenicity.
Both the House and Senate bills would require FDA to determine interchangeability based on whether a biosimilar can be expected to show the “same clinical result” in “any given patient” as the innovator product, and that risks are not increased by switching. Both bills give the first biosimilar to win approval its own period of market exclusivity (one year in the Senate version and two years in the House). While both versions give innovator companies a market exclusivity base of 12 years, the House version adds two additional years for a “medically significant new indication” and six more months in exchange for pediatric studies for a potential of 14.5 years.
“In conjunction with the bipartisan Senate legislation, the Pathway for Biosimilars Act signals an emerging consensus on key issues,” said Donald R. Ware and Kalah Auchincloss, pharmaceutical and intellectual property attorneys with Foley Hoag LLP in Boston. “The result may be an increased likelihood of enactment of comprehensive and balanced legislation creating an abbreviated approval pathway for biosimilars with enhanced incentives for biomedical innovation,” they wrote in a policy paper.
Even if a biosimilars bill were to be passed and signed into law, immediate results are unlikely. This is because the FDA would likely be at least required to develop guidance documents and hold public hearings as part of the regulatory process. In the past, the agency has been notably slow in this area. After holding public workshops in 2004 and 2005, the FDA announced it would issue a white paper on the biosimilars to be followed by guidance documents on policy, technical characterization, and immunogenicity. The white paper came out two years later.
Vaccines under trial
Despite recent setbacks highlighted by last year’s surprising failure of Merck and Co.’s leading AIDS vaccine candidate and, later, the company’s recall of about 1.2 million doses of its Haemophilus b Conjugate and Haemophilus influenzae type B/hepatitis B vaccines over sterility concerns, vaccine development continues apace:
• Tuberculosis. Researchers at the University of North Carolina have successfully tested a new, inhalable form of BCG or bacille Calmette-Guérin vaccine for tuberculosis. Beneficial for developing countries, this version does not require refrigeration, needles or water.
• Meningococcal disease. A new vaccine has been tested in a randomized controlled trial involving nearly 400 infants and found safe and effective against meningococcal disease. If approved, the vaccine could lead to major reductions in meningitis during infancy, when rates are at their highest.
• Breast cancer. Several vaccines are being developed to treat and prevent breast cancer. One promising candidate is undergoing a Phase 1 study at the Sidney Kimmel Cancer Center for recurrent breast cancer. If successful, it would be the first cancer vaccine specifically designed for the aged immune system.
About the Author
Contributing editor Ted Agres, MBA, is a veteran science writer in Washington, DC. He writes frequently about the policy, politics, and business aspects of life sciences.
This article was published in Drug Discovery & Development magazine: Vol. 11, No. 5, May, 2008, pp. 12-14.
Filed Under: Drug Discovery