A study published this month proposes that biosimilars be assessed in a quantitative benefit-risk analysis to assess whether what the authors call “uncertainty in the clinical performance of biosimilars” can be countered by lower pricing.
Development of biosimilars generally involves, as a culminating step, a confirmatory study in the most sensitive population in which the biosimilar is proposed for use. These confirmatory studies, which are undertaken after preclinical models have shown no differences between the biosimilar and its reference, and after pharmacokinetic and pharmacodynamic evaluation has been conducted, are intended to resolve any residual uncertainty that developers or regulators may have about the similarity of the proposed product and its reference. Developers then provide scientific justification to regulators for the extrapolation of indications to disease states other than the one studied in the confirmatory trial.
The extrapolation of indications means that fewer clinical data are available for a biosimilar’s use in some disease states at the time of its launch, and that fact has led some clinicians to voice concerns about using biosimilars in treating diseases in which they were not directly studied in a confirmatory trial. One stated concern related to biosimilars has been the potential risk for increased immunogenicity, though more than 10 years and 700 million patient days of experience with biosimilars have not yielded evidence of such a risk.1
A study published this month proposes that biosimilars be assessed in a quantitative benefit-risk analysis to assess whether “uncertainty in the clinical performance of biosimilars,” primarily with respect to a hypothetical immunogenicity risk, arising from the extrapolation of indications can be “countered by their lower pricing.”2
The paper, published in PharamcoEconomics, used a 1-year decision-analytic model developed for CT-P13 (Inflectra, Remsima), an infliximab biosimilar, for the treatment of Crohn disease (CD). According to the paper’s authors, immunogenicity is a special concern with infliximab in CD as opposed to other disease states.
The authors designed a model of 1-year cost-effectiveness from the UK National Health Service (NHS) perspective. A hypothetical cohort of new starts with moderate to severe CD was simulated through the model. Immunogenicity was a key modifier; the rate of development of antibodies to infliximab were derived from meta-analysis assessing the brand-name infliximab, Remicade. Costs were taken from a 2009 Markov model, adjusted for inflation, and from NHS reference costs.
The base-case analysis resulted in an expected 1-year quality-adjusted life-year (QALY) of 0.803 for both the biosimilar and for its reference, with expected 1-year costs of £18,087 (US $25,109) and £19,176 (US $26,620), respectively.
However, the authors write that, “assuming 50% of patients develop [antidrug antibodies, ADAs] for Inflectra, compared with 12.4% who develop [ADAs] from Remicade,” then the biosimilar would only remain the preferred infliximab option if it were priced below £410 (US $498) per vial, versus £420 (US $510) per vial for the reference. The authors also put forth what they call a worst-case scenario in which 100% of patients exposed to the biosimilar develop ADAs, in which case the price for the biosimilar would need to drop to £395 (US $480) per vial to remain a preferred treatment. (However, the authors acknowledge that a recent head-to-head study of CT-P13 versus its reference in patients with CD, published in The Lancet, did not show any difference between the biosimilar and its reference in the population of patients with CD.3)
According to the current study’s authors, their model provides a basis for the quantitative evaluation of biosimilars to support health technology assessments, and can be used to “protect health systems” from “potential risks of biosimilars” when indications are extrapolated.
References
1. Cohen HP, Blauvelt A, Rifkin RM, Danese S, Gokhale SB, Woollett G. Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. [Published online March 3, 2018] Drugs. doi: 10.1007/s40265-018-0881-y.
2. Catt H, Bodger K, Kirkham JJ, Hughes DA. Value assessment and quantitative benefit-risk modelling of biosimilar infliximab for Crohn’s disease [published online August 2, 2019]. PharamcoEconomics. doi: 10.1007/s40273-019-00826-0.
3. Ye BD, Pesegova M, Alexeeva O, Osipenko M, Lahat A, Dorofeyev A. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn’s disease: an international, randomised, double-blind, phase 3 non-inferiority study [published online, March 28, 2019]. Lancet. doi: 10.1016/S0140-6736(18)32196-2.
Eye on Pharma: BI Cyltezo Partnership; Europe Ustekinumab Launch; Mexico Biosimilar Approval
July 24th 2024Boehringer Ingelheim (BI) partners with GoodRx to offer its unbranded adalimumab biosimilar to patients at an exclusive low price; a new ustekinumab biosimilar launches in Europe; and Mexican officials approve a bevacizumab biosimilar.
Biosimilars in America: Overcoming Barriers and Maximizing Impact
July 21st 2024Join us as we explore the complexities of the US biosimilars market, discussing legislative influences, payer and provider adoption factors, and strategies to overcome industry challenges with expert insights from Kyle Noonan, PharmD, MS, value & access strategy manager at Cencora.
Real-World Study: No Increase in Health Resource Costs After Infliximab Biosimilar Introduction
July 20th 2024Although biosimilars reduce drug purchasing costs for hospitals, it’s unclear whether those savings might be offset by increased health resource utilization following a non-medical switching initiative.
Biosimilars Gastroenterology Roundup for May 2024—Podcast Edition
June 2nd 2024On this episode of Not So Different, we review the biggest gastroenterology biosimilar stories from May 2024, covering new data from conferences and journals on infliximab and adalimumab products that demonstrate positive clinical results and confirm the safety of these biosimilars, as well as the feasibility of switching to them.
Hesitancy in MENA Nations to Adopt WHO Biosimilar Guidelines Hinders Market Development
July 17th 2024The World Health Organization’s (WHO) new guidelines for biosimilar approvals aim to save time and money for manufacturers in the Middle East and North Africa (MENA), but hesitancy among nations to adopt the guidelines is stifling market development of biosimilars.
BioRationality: Time to Get Rid of PBMs if Biosimilars Are to Succeed
July 15th 2024Sarfaraz K. Niazi, PhD, discusses the challenges with pharmacy benefit managers (PBMs) that plague the biosimilar industry and new legislation that attempts to reform their practices and encourage biosimilar adoption.