Yesterday, an FDA advisory committee recommended approval of Celltrion’s infliximab biosimilar, CT-P13, for the same indications as its reference product, Remicade, in the most controversial example of indication extrapolation to date.
After reviewing the same molecule, CT-P13, Health Canada refused approval for Crohn’s disease and ulcerative colitis, although extrapolation of the rheumatoid arthritis efficacy data was accepted for psoriasis and psoriatic arthritis. This refusal was attributed to differences in glycosylation that were considered to have an unknown influence on CT-P13’s effects in these GI indications, where the mechanism of action differs slightly to the rheumatic and psoriatic settings. So, does this mean that the FDA is going to be more receptive to allowing extrapolation than its Northern neighbor, or could it mean that concerns about extrapolation are unwarranted?
Unlike Health Canada, the FDA was privy to additional data, including real-world observational data from CD and UC patients in Europe and South Korea which could have swayed the committee’s recommendation. But regulators are not the only stakeholders that need to be convinced about extrapolation; are physicians ready to take the leap and prescribe a biosimilar without data from a randomized clinical trial in a relevant indication?
Based on initial experience of the first US biosimilar, Sandoz’s Zarxio (filgrastim-sndz), the answer appears to be an emphatic no. Our research with US specialists who manage cancer patients eligible for treatment with Zarxio shows that the leading reason for not prescribing Zarxio is not the modest 15% discount, but concern about indication extrapolation.1 This research was conducted at 1-month post-launch, however, so is there any evidence from Europe that attitudes toward extrapolation might diminish over time?
CT-P13 shares the same label as Remicade in Europe, in spite of the EMA noting the same glycosylation differences that prevented full extrapolation in Canada. Pfizer (previously in the guise of Hospira) has been selling CT-P13 as Inflectra in the major European markets since February 2015, which has allowed us to assess whether gastroenterologists’ opinions about using a biosimilar in an extrapolated indication have shifted over time.
Back in 2014, when neither US nor European gastroenterologists had the option of using an infliximab biosimilar, most surveyed gastroenterologists said they wouldn’t use an infliximab biosimilar if it had only been clinically tested in rheumatoid arthritis. Flash forward to 9 months after Inflectra launched in Germany, and over half of surveyed German gastroenterologists have used Inflectra, despite the fact that Inflectra was only clinically tested in rheumatic diseases.2
Looking back at responses in 2014, US and German gastroenterologists had strikingly similar attitudes toward use of an infliximab biosimilar in extrapolated indications, which could indicate that attitudes of US physicians toward use of biosimilars in extrapolated scenarios will also soften. DRG’s Biosimilars team will continue to track physician, as well as payer attitudes, throughout 2016.
1. Learn more about the performance of Zarxio in the United States.
2. Learn more about the performance of Inflectra in Germany.