The 8th Biosimilars Congregation held in London on March 8th - 9th 2016 provided a venue for fruitful discussion on a number of hot topics in the biosimilars space, in the year which marks the 10-year anniversary of the first European launch of a biosimilar, Sandoz’s Omnitrope (somatropin). The key themes discussed were:
- The generally positive uptake of Celltrion’s CT-P13 (infliximab), marketed as Inflectra by Pfizer and Remsima by Celltrion’s marketing partners, despite being the first monoclonal antibody biosimilar and some concerns about indication extrapolation;
- The potential for demonstration of biosimilarity in the future, with reduced need for large-scale efficacy trials and greater reliance on analytical characterization, functional assays, and PK/PD studies;
- The fundamental need for continuing efforts to gain physician and payer buy-in for biosimilars based on the fact that biosimilars will expand access to biologic treatment in some markets and provide headroom to fund novel emerging therapies.
Despite gastroenterology societies’ initial concerns about the approval of Remsima/Inflectra in inflammatory bowel disease (IBD) based on clinical data from rheumatic indications, gastroenterologists are increasingly prescribing Remsima/Inflectra. Growing real-world data suggesting that outcomes in IBD with Remsima/Inflectra are similar to Remicade has helped promote uptake.
In the Nordic regions, there has been a different driver of uptake of biosimilar infliximab. Orion pharmaceuticals (one of Celltrion’s marketing partners) achieved 87% share of the infliximab market in January 2016 in Norway by offering a 69% discount to Remicade. The unprecedented discount offered enabled the company to win the national infliximab tender for the second year running in 2015 which is the primary reason that Remsima uptake has been so strong, not its real-world data.
However, centralized exclusive tenders are not suitable for all markets and even in small markets like Norway, the long-term sustainability of offering such a substantial discount is questionable. Notably, Orion offered Remsima at a higher cost in the 2016 Norwegian tender compared to 2015, which resulted in Orion losing out to Pfizer which won the tender with Inflectra at a higher price than Orion offered in 2015.
In the less tender-driven markets of Europe, discounts on biosimilar infliximab have been smaller and uptake has been more stunted.
Reducing the Clinical Trial Burden
Further discussion during the conference centred on whether there would be a reduced need to perform Phase III efficacy and safety trials in the future. EMA and FDA guidelines already suggest that efficacy trials may not be necessary if comparability is adequately justified through nonclinical tests and clinical PK/PD, but few companies are omitting efficacy trials in patients.
There are some exceptions; Coherus does not plan to carry out a Phase III efficacy and safety trial for its Neulasta biosimilar CHS-1701. Similarly, Pfenex is aiming for FDA approval of its interferon beta biosimilar based on clinical PK/PD and immunogenicity data. However, all biosimilar insulin developers have opted to conduct multiple Phase III trials, in spite of the fact that the EMA guidance states that efficacy trials of insulin biosimilars are not sufficiently sensitive to detect differences.
The general consensus of speakers at the conference was that there could be a move away from conducting Phase III biosimilar trials, because they are less sensitive to differences between a biosimilar and reference product compared with analytical characterization and PK/PD studies. However, there is a long way to go before physicians will feel comfortable switching to a biosimilar, particularly of a monoclonal antibody, without efficacy and safety data in patients.
Developing Physician and Payer Trust in Biosimilars
A biosimilar developer that chooses to forgo Phase III studies could struggle to gain the trust of physicians and payers who generally remain unfamiliar with other components of demonstrating biosimilarity. Indeed, during the conference it was highlighted that physicians and payers are largely unaware of the batch-to-batch variability of biologics which suggests that there remains a need to provide education about biologics and the approval process for biosimilars, particular focusing on why the analytics and PK/PD studies are more sensitive for detecting meaningful differences than Phase III trials.
Directing education efforts toward all key stakeholders is key to future uptake. Ken Walsh of Evidera observed that, “Health system barriers remain, since payers have not yet effectively managed biosimilar utilization, and aligning financial incentives is a critical driver for the uptake of non-substitutable products”. It is important to address this since budgetary pressures are intense in health systems worldwide and biosimilars can be part of the solution.
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