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Follow-on biologics for multiple sclerosis (MS) drugs such as Teva’s (NASDAQ:TEVA) Copaxone and EMD Serono and Pfizer’s (NYSE:PFE) Rebif are unlikely to happen in the near future, according to a number of industry experts interviewed by Pharmawire. This comes despite both products going off-patent within the next five years.
Although it remains likely a pathway for the approval of follow-on biologics will be included in any final health care reform bill, the process will be too difficult to expect any competition to emerge in the space in the near term, according to sources in Washington.
Most recently, innovators were given a boost when the Senate Health, Education, Labor and Pensions Committee (HELP) passed an amendment allowing for 12 years of data exclusivity, substantially more than some originally expected. And in the House, it now appears a proposal from Rep. Anna Eshoo (D-CA), which also includes 12 years data exclusivity, will be favored over a proposal from Rep. Henry Waxman (D-CA), according to an attorney following the progress of the debate. Just as importantly, the likely requirements on clinical testing will make follow-on biologics closer to developing an improved product than a classic generic, the attorney said.
Jayson Slotnik, an associate at Hogan & Hartson closely following the health reform debate, said he agrees a pathway will likely be included in any final bill. But Slotnik also said it would be years before any product makes it to the market. In the MS space, where competition already exists, Slotnik said it was hard to see FOBs making an impact for a very long time. “Outside of EPO no one knows where the market makes sense for many, many years,” he said. “From a business perspective we’re fighting over a principle.”
Copaxone continues to be the leading relapse-remitting MS therapy in the US and globally, with Q2 up 21% compared to the second quarter of 2008
In July 2008, the FDA accepted Momenta/Sandoz’s ANDA for a generic version of Copaxone. Teva has seven US Copaxone patents covering chemical composition and methods of use, which expire in May 2014. Rebif is scheduled to go off-patent in 2013.
Although the FDA regulates Copaxone as a drug - and not a biologic - its manufacturing process is highly complex, and a generic version could face problems in demonstrating comparability with the innovator.
”Given the complexity of Copaxone and the inability of state of the art methodology to fully characterize the multiple active ingredients in the product, it is Teva’s position the only way to ensure a product has no significant clinical differences in safety, efficacy and immunogenicity would be through full-scale, placebo-controlled clinical trials with measured clinical endpoints,” according to a Teva spokesperson.
”When it comes to MS, and the potential for follow-ons, it is very complex and there are many things to consider,” said Dr Jerry Wolinsky, a consultant to Teva and the Bartels Family and Opal C. Rankin Professor of Neurology at the University of Texas Medical School at Houston.
Wolinsky, who recently co-authored a paper in Neurology discussing this topic, highlighted in this paper that it may be necessary to demonstrate free substitution directly in clinical studies that show that repeated switching between an FOB and its innovator has no negative clinical impact on safety or efficacy.
These issues may be particularly relevant for FOBs for current MS biologics, according to his recent paper, as among the three available interferon beta innovator biologics, there are (intentional) manufacturing differences in the bioreactor/cells in which the products are produced, amino acid composition, and post-translational modifications such as glycosylation. There are a lot of discussions ongoing about follow on biologics and setting the appropriate guidelines for this process.
The issue of follow-on biologics is beyond the usual expertise of people in Congress, said Wolinsky. ”There is some legislation that is pending, but it probably will only set the overall guidelines within what the FDA should operate,” Wolinsky said. The FDA will then come up with its own policies in terms of how regulators are going to operate within the Congressional mandate. ”I’m sure there must be ongoing discussions on these within the FDA in anticipation of the legislation.”
“The Hill always has a lot of issues to deal with. This is one that probably isn’t always seen as on the top of the agenda,” Wolinsky said. Whatever enabling legislation the FDA will have from Congress to go forward will likely be a ”sketch” rather than providing all the details.
The FDA, undoubtedly, will then follow with draft position papers, and then come forward with its own guidelines on how pharma should behave, according to Wolinsky. ”Each one of these FOBs, when they come forward to FDA, will likely have the same kind of experience that innovative drugs have had.”
David Peterson, a director of GMP and quality systems at Kaplan EduNeering, a provider of compliance and knowledge management solutions, said companies are claiming that their biologic is identical, when in all probability it is not.
”It’s almost impossible to replicate a biologic. When I was at Pfizer, I headed up a lab on biologic testing,” Peterson said. One particular drug, which prevented kidney transplant rejection, had approximately 40 steps in the manufacturing process, and used all kinds of different animal proteins and purification methods. ”I don’t know how anyone can come up with [copying] that manufacturing process. You’ve got hundreds or components in there; it’s not possible,” he said.
The FDA may look to Congress for guidance, but it is ultimately up to the agency to determine what clinical trials or data it will want to see regarding the safety and efficacy of follow-on biologics, Wolinsky noted.
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