On July 24, 2020, we still await the first FDA-designated interchangeable biosimilar. This may not be a surprise: All of the biosimilars launched to date are administered in the physician’s office, hospital, or outpatient clinic. Without pharmacy distribution, there can be no automatic substitution, the prize at the end of this journey.
The last time we addressed interchangeability in earnest on this piece of Web real estate was more than 2 years ago. Then, in October 2018, we followed Boehringer Ingelheim’s quest for the elusive designation for Cyltezo®. The company’s phase 3 VOLTAIRE-X study was underway. The hope was that this pharmacokinetics and switching trial would check the remaining boxes for FDA.
In that article, we interviewed Molly Burich, MS, Boehringer’s Director of Public Policy. The listing on the government’s ClinicalTrials.gov website indicated a study completion date of July 2020. In preparing to write today’s post, a visit back to the VOLTAIRE-X page noted that the trial was actually completed in April 2019 after enrolling 259 patients. Unsure of whether there was an error, we reached out to Ms. Burich earlier this month, who confirmed that the study was indeed completed. “We’re in the process of submitting data for presentation,” she said in an Email. “We continue to have conversations with the FDA to confirm next steps for filing for the designation.”
Not reading very deeply into the response, it is clear that an official filing has not yet occurred. The purpose of this article is not to speculate on the content of those conversations between the FDA and Boehringer. The wait continues. There is really no rush, however: Cyltezo’s launch is not scheduled until July 2023, and no other manufacturer of an eligible biosimilar has publicly announced the intention to seek the interchangeability designation.
SWITCHING, INTERCHANGEABILITY, AND OFFICE-ADMINISTERED BIOLOGICS
For now, the problem boils down to whether a Part B or office-administered biosimilar product can be easily and safely switched for a reference product. Today, it is no longer a question of safety—ample evidence exists to support the use of biosimilars in place of originator drugs. This point was driven home and put to bed by Barbier and colleagues’ May 2020 review of 178 biosimilar switching studies. This analysis revealed virtually no adverse events or drop in efficacy amongst the trials.
Hillel P. Cohen, PhD, Executive Director, Scientific Affairs, Sandoz, went one step further today, stating during an Academy of Managed Care Pharmacy webinar, “From a science standpoint, there is really no reason why one biosimilar cannot be switched for another.” He indicated that there were perhaps 3 peer-reviewed studies and 3 abstracts (regarding filgrastim, infliximab, and etanercept) studying this question.
One reason for the more limited evidence of biosimilar-to-biosimilar switching is the small number of drug categories with sufficient competition. This is growing, with the addition of multiple trastuzumab and bevacizumab biosimilars launching in the last 12 months. Biosimilar-to-biosimilar switches will likely be the more important topic henceforth, as individual payers begin to prefer one biosimilar to the reference product or another biosimilar. When people inevitably switch health plans over time, biosimilar preferences, as listed on the drug formulary, will change.
Without an interchangeability designation and a strict policy, biosimilar coverage policies are still being enacted. Some payers, like Kaiser Permanente, are demonstrating a clear preference for biosimilars over reference products. The extent to which these policies apply to treatment-naïve patients and established patients vary, but in Kaiser’s case anyway, the health plan expects all patients to be switched to the preferred biosimilar.
Without this type of commitment, biosimilar switches may more likely be driven by patient–physician conversations, particularly around out-of-pocket costs. As Dr. Cohen emphasized in his presentation, interchangeability is only a regulatory construct. “Physicians can prescribe whatever product they believe is appropriate for their patients.” If they believe that a biosimilar is interchangeable or “switchable” with a reference product, they don’t have to wait for the FDA to issue an interchangeability designation. They just have to believe that prescribing the biosimilar product (whether covered by the medical or the pharmacy benefit) is in everyone’s best interest.
Overall, there seems to be less physician resistance to biosimilars in the US than a few years ago. It is more a question of physician incentives to prescribe them (or patients to request their use). The ability to employ interchangeability is in the hands of physicians. The ability to mandate switching is in the hands of whoever makes the coverage decision.