Also pending is an application for ABP-215, a biosimilar version of Avastin that Amgen and Allergan are developing. The companies said a BLA submitted in November was based on data from a phase III trial demonstrating comparable efficacy, safety, and immunogenicity between the ABP-215 and Avastin in adult patients with nonsquamous non–small cell lung cancer.16
Further details have not been disclosed.
One question that has emerged about biosimilars is whether findings from an equivalency trial in 1 indication can be extrapolated into an approval for other disease settings in which the reference product has been approved. For instance, Zarxio, the biosimilar version of Neupogen, has been approved for the same indications as the original drug, while patent protections have prevented similarly extensive labeling for copies of at least 2 other branded drugs, according to Friends of Cancer Research.17
Although would-be biosimilar candidates might be able to demonstrate statistically identical perfor- mance on trials with hundreds of patients, that evidence is not enough to win biosimilars the sort of approval that many observers think they need to bring real competition to the biologic market: approval as interchangeable agents. Under the pathway for biosimilars approved in 2009, the FDA rst determines whether candidates must meet technical and clinical standards as “highly similar” products and then decides whether they are interchangeable.
Thus far, none of the biosimilars approved in the United States can be freely substituted for reference products the way that generic drugs can be freely substituted for name brand drugs in most states because they have not been deemed to be interchangeable. If a doctor prescribed “Neupogen,” a pharmacist cannot look at a patient’s drug plan and give the patient “Zarxio” to reduce the co-pay. Even if the doctor prescribes the theoretically generic “filgrastim” the pharmacist cannot use the biosimilar because the differences in its structure led it to receive a slightly different generic name, “filgrastim-sndz.”
In January, the FDA released long-awaited draft guidance on what it will likely take to earn interchangeable approvals: additional trials that involve patients switching back and forth between the reference drug and the biosimilar.18
“In order to meet the higher standard of interchangeability, a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product,” FDA spokeswoman Sandy Walsh wrote in an email.
Meanwhile, regulations for substituting biosimilars for branded drugs on prescriptions, which are controlled at the state level, have been debated throughout the country and 27 states have now enacted laws, according to the National Conference of State Legislatures.19 Most states agree that the FDA must recognize a biosimilar as interchangeable before it can be substituted for a branded product and that the prescribing physician would be able to prevent substitution by specifying “dispense as written” or “brand medically necessary.”19
Ginestro and other analysts believe that biosimilars cannot reach their full price-saving potential unless it is easy to substitute to the less expensive product at the point where it is dispensed. Physicians would be hard-pressed to keep track of which competing products would be the least expensive in any particular month and keep changing their scripts accordingly, particularly when the most cost-effective brand might vary from patient to patient, based upon each patient’s insurer.
“The field of oncology is a potential bright spot in this respect because most biologic medications are given in the office. Practices would have a strong incentive to shop around for the cheapest comparable product, just as they shop for the cheapest provider of paclitaxel rather than buying Taxol,” said Harold J. Burstein, MD, PhD, an oncologist at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School. “Cancer patients will get value-based care when the person writing the prescription is guided by the best medical information, and then chooses between equivalent options based on price.”
It might be some time before such options are available, not only because the approval process is lengthy and expensive, but also because the makers of reference products have fought aggressively against biosimilar products in the courts.