MOUNTAIN VIEW, Calif.—Noting that Teva and Lonza haverecently terminated their 2009 joint venture agreement to co-developbiosimilars based upon the realization that the development costs and time tomarket were beyond initial estimations, Frost & Sullivan Senior IndustryAnalyst Deborah Toscano observes: "When biosimilars were first a hot topic, itwas a common perception that the scenario would parallel producing generic copiesof conventional small-molecule drugs, which can typically steal up to 90percent of the originator drug's sales with miniscule development costs, bycomparison. When you combine this erosion potential with the high price tags ofbiologic drugs, you get a seemingly easy path to billion dollar revenues.However, as many companies are realizing, copying a biologic drug close enoughto pass regulatory standards is proving to be more technologically andeconomically challenging than originally thought."
Case in point: In Europe, where biosimilars are marketed,they have garnered a meager 11-percent market share. Toscano notes that manyU.S. companies are still awaiting final U.S. Food and Drug Administration (FDA)guidance. She cites a case where a patient died after taking a biosimilar.
"There are many issues at stake, most importantly patientsafety," she says. "One amino acid can throw the immune system off. Successfulbiosimilars will not only have to pass regulatory muster, but will also have toearn the confidence of the prescribing physicians who will rely on strongclinical data and not necessarily only on FDA approval, since they will not be,by definition, identical to the originator biologic drug."
Safety issues are of sufficient concern that Genentech hasissued a formal statement, which says in part that switching between aninnovator biologic and a biosimilar "should only be done followingdemonstration through clinical studies that switching back and forth … causesno greater harm than using the innovator alone." The statement adds anothercautionary note by stating that "each claimed indication for a biosimilarshould be established by indication specific clinical trials, unless there is asolid scientific rationale to justify extrapolation of the clinical safety andefficacy data from one indication to another."
If this sort of scenario prevails, the required costs andexpertise behind the advanced technology, clinical trials, regulatorynegotiations and marketing efforts may be beyond the capabilities of manywould-be biosimilar players. Additionally, as Toscano points out, others maydecide that application through the full Biologics License Application (BLA)pathway or development of biobetters rather than biosimilars makes better financialsense because the overall development costs may not be significantly differentin the long run—and a BLA provides 12-year patent protection.
In Europe, twocompanies have recently been granted marketing authorization for a biosimilarmonoclonal antibody: Celltrion for Remsina, and Hospira for Inflectra. Both arebiosimilar versions of Remicade (infliximab) marketed by Merck and Johnson &Johnson. While some are exiting the playing field, other larger, moreexperienced companies such as Sandoz (Novartis), Hospira and Pfizer are forgingahead.
"Sandoz and Hospira already have vast experience launchingbiosimilars in Europe and elsewhere, giving them a significant advantage overless experienced players," Toscano says. "Sandoz is running several late-stageclinical trials ahead of the FDA's final guidance, and Pfizer has initiatedseveral early-stage clinical trials for their versions of blockbustermonoclonal antibodies such as Herceptin, Rituxan, Remicade and Humira. Likewise, Eli Lilly, no stranger toinsulin therapy for diabetes, has initiated two late-stage trials of theirversion of Lantus, the blockbuster long-acting insulin from Sanofi."
As of June, the FDA had received no applications, but hasreceived requests to meet with various biosimilar developers, stressing theneed to meet early and often. The agency has still not ruled out dealing withbiosimilar issues on a case-by-case basis and continues to emphasize that theywill weigh analytical data very highly and maybe back off on the requirementsfor clinical trials to some extent. Yet another unknown: once biosimilars areintroduced, will third-party payers in effect force physicians to prescribethem?