The sessions from the Drug Information Association Biosimilars 2020 virtual meeting held earlier this month touched on some very important points for the biosimilar community. In addition to our previous meeting report, I thought some others needed to be mentioned briefly, with a bit of commentary.
One Biosimilar Class That Poses Difficulties for Comparative Pharmacokinetic Analysis
Andrea Laslop, MD, Head of Scientific Office, Austrian Medicines and Medical Devices Agency (AGES), Austria, reminded that in consideration of efforts to streamline the biosimilar development and approval process, some biologics may require special considerations. She pointed to locally acting biologics like ranibizumab, aflibercept, and dornase alfa. When these agents are utilized, they result in “very low systemic levels, which makes a comparison of [pharmacokinetic] endpoints between the biosimilar and reference product very difficult.” She believes that pharmacodynamic endpoints in comparative studies may be used to compensate for this gap in the analytical data.
Comment: Both ranibizumab and aflibercept, ophthalmologic agents, are undergoing active biosimilar development for the US market, and these prospective manufacturers generally have planned or are in the midst of phase 3 trials. For these next-wave biosimilars, the Food and Drug Administration (FDA) may decide to weigh the phase 3 trial results a bit more heavily than for other systemic biosimilars, just for this reason.
Countering Negative Anecdotal Biosimilar Reports
Ali McBride, PharmD, MS, BCOP, Clinical Coordinator, University of Arizona Cancer Center and President of the Association of Community Cancer Centers, reminded attendees of the continued importance of biosimilar education. “I’m still hearing questions about why clinical studies haven’t occurred for extrapolated indications,” he said. Some of the negative information about biosimilars comes from small or anecdotal studies, according to Dr. McBride. We need to counter these reports with greater education: “Pharmacovigilance (including national registries and Medwatch reporting) will have a big role in addressing these one-off reports.”
Comment: Publication of any case studies or negative outcomes associated with biosimilars has been sparse, and certainly overwhelmed with information about successful switches, positive clinical trial results, and impressive cost savings. Dr. McBride is right, however, in that published pharmacovigilance data will help further establish the quality of biosimilars. Expect the BBCIC to be a greater player in this effort.
Workflow Challenges to Onboarding Biosimilars
Dr. McBride also covered the practical aspects of incorporating biosimilars into practice. He made an excellent point about the workflow challenges: “EMR implementation can actually be more difficult than obtaining P&T review!” Rya Haumschild, PharmD, MS, Director of Pharmaceutical Services at Emory Healthcare, agreed, “Updating the EMR is so important and time consuming when adding a biosimilar.” Dr. McBride pointed to the problem of incorrect order entry, which includes not only using the wrong drug name (though EMRs have done a good job of addressing the four-letter suffixes), as well as E-prescribing chargemaster elements, like dosing and drug quantity.
In the case of pegylated (long-acting) filgrastim, “every physician will refer to Neulasta® but very few will specifically designate OnPro®,” he said. This causes more issues for the finance department than it does for patient care (because they think all of these patients are receiving the prefilled syringe formulation). There is the separate issue of stocking multiple biosimilars based on different health plans’ formulary preferences.
Comment: Incorporating biosimilars into the everyday workflow of a practice is critical to smoothly increasing uptake of biosimilars. Yet, this topic is rarely covered in detail. It is good to hear that EMR vendors like EPIC have been meeting this challenge.
Role of Pharmacists in Biosimilar Education
Shubha Bhat, PharmD, MS, BCACP, Ambulatory Care Clinical Pharmacy Specialist—Gastroenterology, Center for Digestive Disorders and Crohn’s and Colitis Program, Boston Medical Center (BMC), described the BMC’s transition from Remicade® to Inflectra®, which was approved by the medical center’s P&T Committee in December 2017. Pharmacists were at the forefront of gaining the physician’s buy-in for the program, which included clinical monitoring of patient outcomes, switching to the biosimilar for patients whose conditions were stable for at least 6 months (or naïve to treatment). From March 2018 to June 2019, 97% of eligible patients were given the biosimilar. Only five patients did not transition to the biosimilar (discontinued infliximab treatment or lost to follow-up). Dr. Bhat noted, “None of the discontinuations were related to the biosimilar switch. Our real-time monitoring of patients revealed no differences in outcomes or safety.”
Comment: The pharmacist’s role in terms of drug information and biosimilar education cannot be overemphasized. Health systems and health plans have learned to rely on pharmacists to help ease any concerns prescribers may have regarding biosimilars. And not only P&T Committees but individual prescribing physicians need their expertise in transitioning programs like this one.
Orphan Biosimilars Pose Analytic Challenges
There is no guarantee of financial success when developing orphan biosimilars, and Dr. Laslop raised an additional practical issue that may raise the stakes further. Under current regulatory guidelines, clinical noninferiority studies of biosimilars generally that the biosimilar perform within 10% or 15% equivalency margins in terms of efficacy and safety. With some biologics to treat orphan diseases (like eculizumab or romiplostim), the number of available patients for study is much smaller than for rheumatoid arthritis or breast cancer, for example. Therefore, Dr. Laslop said, “The low number of patients precludes stringent equivalence margins and the development of a comprehensive safety database prelicensing.” This is a very good point and may mean that other (unspecified) statistical approaches in comparative trials may be more useful in the assessment of orphan biosimilar candidates.