Welcome Zarxio, the Sandoz version of filgrastim. While nothing is “easy” when it comes to drug development, many view this initial Sandoz experience as forecasting clear skies and fair winds for every biosimilar put in front of the agency for consideration.
If you believe that, there’s a bridge in Brooklyn you might find of interest.
The filgrastim example is an n of 1 and shouldn’t be viewed as predictive of anything other than the FDA approval for one product.
As surely anyone inside the agency or at Sandoz will tell you, the pathway to approval has been anything but easy. But that hasn’t stopped the sale of rose-colored glasses to many. So be it.
More important to consider is how the agency will continue to study global biosimilar experiences – and especially in the EU.
Case in point: Remicaide (infliximab), certainly a product on the radar screens of many as the next big biosimilar marketing opportunity – and regulatory challenge.
The Remicaide road has been a rocky one in the EU. A new poster presentation at the European Crohn’s and Colitis Organisation, titled, “Biosimilar but not the same,” offers some timely and important real-world data on the differences between originator biologics and their biosimilar cousins.
The study, from Mercy University Hospital, University College Cork, Centre for Gastroenterology, Mercy University Hospital, Cork, Ireland, studied the clinical impact of both the innovator product (Remicade) and it’s EMA-approved biosimilar (Inflectra). The findings are important. Specifically, the rates of surgery in Infliximab and Inflectra groups were significantly different.
80% of the Inflectra group required hospital readmission versus 5% of the infliximab (Remicade) group. (p=0.00004). 60% of patients in the Inflectra group needed steroid augmentation of standard steroid tapering protocol with 50% requiring multiple increases in steroid dose versus 8% of patients in the Infliximab (p-value = 0.0007). Over the course of 8 weeks, 93% of patients in the Inflectra group had an increase in CRP with 7% remaining unchanged whereas 100% of patients in the infliximab group had a decrease in CRP (p=<0.001).
The conclusion is not ambiguous, “Our results suggest that biosimilars may not be as efficacious as the reference medicine. The results found reflect the ECCO statement position that the use of most biosimilars in IBD will require testing in this particular patient population and cannot be extrapolated from other disease populations."
And now the British Society of Rheumatology (BSR) is calling for clinicians to register patients with its biologics registers to track the efficacy and long-term safety of new biosimilar products coming on to the UK market.
The BSR – the professional association for health professionals involved in rheumatology and muscular skeletal disease – maintains two biologics patient registers. One is for people being treated for rheumatoid arthritis, the other for patients with ankylosing spondylitis.
The BSR has released a position statement on biosimilars and says that it supports their introduction but wants to make sure that a system is in place to monitor their safety and efficacy in order to reassure health professionals and the public.
“Widening the range of treatments available to our patients at a lower cost to the NHS is clearly a positive step, but there are still a few gaps in the evidence for the safety and efficacy of these products, which will need to be explored further,” says Alex MacGregor, chair of BSR Biologics Registers.
“For example, the clinical trials of these drugs for people of rheumatological or autoimmune diseases were with new users only, and no trials have explored the effects of substitution from a reference drug.”
The release of the BSR’s position statement comes as biosimilar versions of Janssen Biologics’s Remicade — a medicine that contains the monoclonal antibody infliximab and is used for a variety of inflammatory conditions including rheumatoid arthritis — are being launched in the UK.
These First World data points about a product from a respected manufacturer (Hospira) cannot be ignored and must be used to inform the policy debate over nomenclature, interchangeability, label extrapolations, and overall pharmacovigilance practices. Surprising? Not if you understand that the decision tree for biosimilars is quite different from the Hatch-Waxman pathway. And that for the foreseeable future, each biosimilar application is going to be an important learning experience for FDA reviewers and senior division staff.