Worth the Trouble?
“The entry barrier for biosimilars, in many cases, will be the money companies can afford to spend on clinical trials,” observes Paul Wotton, Ph.D., president and CEO of Antares Pharma, which specializes in biosuperiors based on enhanced delivery. “Faced with the prospect of long development times for a biosimilar, and uncertain revenues, companies may decide that a biobetter would be more worth their while.”
Another doubter is Bassil Dahiyat, Ph.D., CEO of Xencor, who describes biosimilars as a “low-risk, low-reward strategy,” while biosuperiors are “higher risk, higher reward.”
While clinical risk for biosimilars is lower than for biosuperiors and new biological entities, it is not zero. Add to that manufacturing start-up costs, human testing requirements, uncertain reimbursement, competition, no pharmacy-level substitution, the burden of demonstrating similarity, and the almost assured need to employ a BLA-like sales and marketing force.
“A good case could be made to stay out of the biosimilars business altogether,” he explains, “particularly for complex molecules like antibodies.”
Most approved biosimilars are hormones and cytokines. Last autumn, EMEA released guidance on generic monoclonal antibodies, several years after issuing rules for somatropin, G-CSF, erythropoietin, alpha interferon, and insulin. Fourteen drugs have been approved under these guidelines. United States approvals amounted to four hormones: HGH
(Omnitrope®/Sandoz), calcitonin (Fortical nasal spray/Upsher-Smith), hyaluronidase (Hylenex/Baxter), and glucagon (GlucaGen pen delivery system/Novo Nordisk). All have a long history of safe use and were approved under the 505(b)(2) designation usually associated with generic small molecule drugs.
Teva, known for its small molecule knockoffs, has been selling its version of Amgen’s Neupogen (filgrastim) in Europe since 2008. The eponymously named product, TevaGrastim, was approved under abbreviated BLA-like tracks but U.S. approval, which has been delayed for about 18 months, is expected under a full-blown BLA.
Interestingly, the downside to Amgen is limited since it has already moved on to a biobetter. U.S. sales from Neupogen total $900 million, while revenue from Neulasta, a PEGylated version, exceeds $2.5 billion.
“The tumor necrosis factor market is one big biobetter,” notes Sonny Gal, Ph.D., senior analyst at Bernstein Wealth Management. These include the antibody TNF blockers Enbrel, Humira, and Remecaid.