Remember Leslie Nielsen’s character, Officer Frank Drebin, in the first Naked Gun movie, admonishing bystanders who were watching a catastrophe of explosions behind him, “Nothing to see here, folks. Please disperse. Nothing to see here”? Well, with biosimilar clinical trial results, there really hasn’t been anything new to see here.
In the early days of biosimilar approvals and utilization in the United States, there was keen interest regarding data detailing how the products performed against reference agents in clinical trials and in the real world. As the FDA required phase 3 trials for many of these new biosimilars, plenty of data were reported, and it was consistently newsworthy. It was the bulwark of basic education on biosimilars for payers, providers, and patients. In addition, the regulatory agencies still relied on these clinical trial data to fill in their evidence gaps and increase confidence in the totality of information on hand. Â
At BR&R, it’s been quite a while since I published clinical trial results for a particular biosimilar. I’m not sure the new data are newsworthy today. Two related factors are influencing my thoughts here: (1) These trials don’t find significant variances in terms of biosimilar effectiveness or safety compared with the reference product and (2) the FDA is moving towards no longer requiring phase 3 clinical trials for biosimilar approval.
Asked and Answered: Biosimilars Are Safe and Effective
The clinical trial data, reported by investigators supported by or working for the biosimilar manufacturers have become tediously the same, in a good way. Invariably, the biosimilar drug is found to be equivalent to the reference agent in terms of safety and efficacy. In real-world studies, there is sometimes variance in the percentage of patients discontinuing biosimilars vs. reference products, and some of this variance is attributed to the nocebo effect. With boring regularity, outside of anecdotal case reports, biosimilars have not been associated with significantly lower efficacy or greater adverse events than their reference products.
The question of biosimilar safety and efficacy was such a frequent concern that it was part of the original mission of the Biosimilar and Biologics Collective Intelligence Consortium (BBCIC), which researched and reported on real-world health plan–generated data on emerging biosimilar utilization. This mission was vital to instill confidence in payers, providers, and patients that biosimilar use will not have negative outcomes. The publication of these clinical data, especially in drug categories or specialties new to biosimilar prescription, is still important. It’s just not very newsworthy these days.
From US and European evidence published to date, biosimilar use appears to have only one true outcome that is different than the reference product—biosimilars cost less (and in some drug categories, a lot less).
The Clinical Trial Requirement Is Coming to an End
Quite a while ago, the FDA began accepting this reality. They began to not require new clinical trials for some biosimilars. And they have signaled the intention to move away from the clinical trial requirement for most new biosimilar applications. Partly, this was due to their experience and the fact that randomized phase 3 trials of biosimilars, as designed, were not nearly large enough to demonstrate significant differences in outcomes between the biosimilar and reference drug (and they were plenty large and expensive already).
And here we are today. I generally pass on publishing new biosimilar clinical trial results in established drug categories, simply because they have low news impact. Biosimilar utilization will not be affected by them. They add to the widening evidence base that says the same thing, with each new addition: Biosimilars work.
Certainly, based on what we know today, Frank Drebin was right with regard to the results of biosimilar clinical trials.
