As I wrote yesterday, there’s every indication that generic biologics are coming – as far as Congress and the FDA are concerned, it’s just a question of how and when. But some leading biotech companies that market brand-name biologics see generic competition as a threat – and are using a number of strategies to derail them.
At the FDA meeting on scientific issues held earlier this month, Amgen called for a high standard in approving “follow-on” biologics:
Drugs produced by biotechnology "are unique products," Kenneth Seamon, Thousand Oaks-based Amgen's vice president for global regulatory affairs, told the FDA officers at the meeting in Gaithersburg, Md. "They must be held to the same high standards of safety, purity and potency as the innovator to insure patient safety."
Amgen urges caution in clearing biotech generics, Bloomberg News, 09/16/04
Amgen is the world’s largest biotech firm – according to Business Week, Amgen markets five drugs that each generate at least $1 billion in sales annually. Amgen’s blockbuster drugs include Aranesp (darbepoetin alfa), used to treat anemia – sometimes used during hepatitis C treatment to offset the side effects of ribavirin. Epogen and Procrit, other anemia drugs, are losing some of their patent protection this year, potentially clearing the way for generic versions. Amgen also markets Neupogen (figrastim), a drug sometimes used during hepatitis C treatment to offset certain side effects of interferon.
Meanwhile, another leading biotech, Genentech, filed a petition in April that ‘asks the agency to refrain from publishing the guidance, or approving generics of any Genentech drugs, because the company claims it would be impossible for the FDA to do so without infringing on Genentech's trade secrets. "We draw the line at agency reference to or reliance on Genentech trade secret and confidential commercial data and information to approve a competitor's product," the petition states.’ Genentech makes a brand-name version of human growth hormone – the drug for which Sandoz had developed a generic version, Omnitrope (see Genentech's Generic Battle, Forbes, 05/05/04).
The Biotechnology Industry Organization (BIO), biotech’s trade industry, claims that “minor changes in the biologic manufacturing process can result in unexpected alterations of the final product” at the recent FDA meeting (see BIO Comments On Follow-On Biologics Will Include Manufacturing Anecdotes, FDAAdvisoryCommittee.com, 09/17/04). BIO is poised to play a leading role in the generic biologics debate. This summer, Rep. James Greenwood (R, PA), a leading House critic of the pharmaceutical industry, announced that he will become the new president of BIO at the end of his term.
The FDA, for its part, expressed skepticism at Big Biotech’s arguments:
FDA raised concerns that innovators would have the agency establish a higher regulatory hurdle for follow-on biologics than is required for the innovator product.
“For post-approval changes, manufacturers routinely change master cell banks, they may make formulation changes, and they never demonstrate comparability. How can you justify a full-blown clinical study would need to be done for a follow-on biologic?” FDA Division of New Drug Chemistry II Chemist Janice Brown asked.
“Given the extensive amount of information out there on innovator products, some that have been on the market for 10 years, with well known both therapeutic effects and adverse effects, is there anything in all of that data, published and potentially available for study of the innovator’s product, that would...allow for any lesser degree of study in order to gain approval?” Rosenberg asked.
“That is something you’d have to assess on a case-by-case basis,” Pharmaceutical Research & Manufacturers of America VP-Scientific & Regulatory Affairs Caroline Loew responded.
So this is biotech’s strategy: deny access to data needed for comparison studies, raise the bar of approval so high that there’s no economic incentive for developing generic biologics, and sow confusion into the debate wherever possible.
Complicated webs of patents also pose a hurdle for generic biologics. Most drugs are covered by several layers of patents, and “innovator” companies can extend the life of their patents by modifying the original drugs to make them more effective or longer-lasting. For example, Aranesp is a longer-acting erythropoietin which can be taken less frequently from standard forms like Procrit.
That’s what’s happened with interferon – the original interferon patents were filed over 20 years ago, but newer pegylated versions of interferon are still under patent protection. In theory, companies could develop generic versions of standard interferon, but they wouldn’t be able to compete with the longer-lasting pegylated versions.
According to industry analyst Datamonitor, at least 10 biogeneric companies have looked to develop generic interferons, but “several of the biogenerics companies that had been developing versions of Schering-Plough's Intron have now discontinued development, as most patients are now prescribed PEG-Intron, the extended release version.” (Omnitrope deferral casts doubt over biogeneric development, Datamonitor, 092104)
Finally, even generic versions of pegylated interferon and other biologics used in hepatitis C treatment (e.g., EPO and Neupogen) won’t lead to rock-bottom prices. Whether brand-name or generic, these drugs will still be expensive to manufacture.
But pricing competition through generic biologics would ultimately lower prices, making treatment more affordable and accessible. And some companies marketing generic versions of ribavirin – notably Novartis' Sandoz and Teva – are considered leading contenders if and when a generic biologics market emerges. That’s why the hepatitis C community should keep a close eye on developments in the on-going debate around generic biologics.
The next major forum for discussing these issues will be at a web conference on October 6th & 7th sponsored by the Drug & Devices Dialogue, Following On Hatch-Waxman: Credentials for Success. Senators Hatch and Waxman will both speak about the impact and future of their Act, and its implications for generic biologics.
See also presentations from the September 2004 FDA public workshop.