Since the inauguration of Donald Trump as the President of the United States, the pharmaceutical industry — and particularly the biosimilar industry — has been facing uncertainty over a number of possible changes. For a few months, there were concerns about the repeal of the Affordable Care Act, and with it the Biologics Price Competition and Innovation Act (BPCIA). After a number of congressional hearings, Congress has been tasked with the reauthorization of the Biosimilar User Fee Act (BsUFA II), and Amgen vs. Sandoz has appeared before the Supreme Court — not long after the appointment of Justice Neil Gorsuch.
In addition to the long-awaited and highly anticipated Supreme Court hearing, the potential appointment of Scott Gottlieb as the new FDA commissioner has garnered its fair share of attention since March. Despite Trump’s and other potential nominees’ emphasis on bringing drastic changes to the FDA, Gottlieb has been considered a more conventional choice to run the FDA.
But the biosimilar industry has its own questions about how the new commissioner could shape the FDA and the biosimilar development process. There has been an intense focus on streamlining and bolstering the efficiency of the FDA’s overall drug approval process. But in addition to these talks on the agency level, the concept of an even-more-abbreviated biosimilar development process has become a big talking point among biosimilar makers. It’s unlikely biosimilar applications containing only analytical and preclinical data will meet the FDA’s demands for totality of the evidence within the next few years. However, the upcoming appointment of a new commissioner and political demands for quicker development and lower drug prices have only intensified the discussion within the biosimilar industry about developmental efficiency.
New FDA Commissioner, New Biosimilar Data Expectations?
It’s been a few months since I attended the IQPC Biosimilars Analytical Similarity, Clinical Studies, and Market Entry conference. But after reading a tweet about the upcoming confirmation hearing for Gottlieb, I was reminded of a panel discussion that took place at the IQPC event. The topic of discussion circled around the regulatory changes taking place within the biosimilar space and what biosimilar makers should expect moving forward.
During this panel discussion, Rakesh Dixit, VP of R&D for AstraZeneca, expressed his uncertainty about what role the new commissioner will play and how he’ll approach biosimilar guidelines. (At the time of the conference, Gottlieb had not yet been nominated, so Dixit’s comments were not specifically focused on Gottlieb.) But in the face of chatter about a quicker FDA, it’s only natural questions would arise within the industry about how much (or how little) clinical data a biosimilar company may need to show for approval in the future.
“Perhaps the new commissioner will say, ‘We don’t need any clinical data,’” Dixit posed.
“He could instead emphasize just pharmacokinetics and pharmacodynamics [PK/PD]. Or, there’s always the possibility he could go in the opposite direction and argue the need for more trials.”
To Dixit, where the new commissioner will fall on this spectrum is one of the forefront regulatory questions that could impact biosimilar development moving forward. But should biosimilar makers be prepared to present more data than before when proposing a new biosimilar? Members on the panel say no — but, of course, there are shades of grey within this answer.
In this rather diverse space that is made up of a variety of companies — from Big Pharma to pure-play companies — it’s important to consider that the definitions of what constitutes “more data for biosimilar development” are likely to vary. For instance, Bruce Leicher, the general counsel for Momenta Pharmaceuticals and president of The Biosimilars Council, argued on the IQPC panel that the answer to whether companies will have to present more data all depends on the company’s development strategy.
“Companies that may have relied on clinical data in the past may feel they’re presenting more data in the future because they’re doing more analytical and functional work,” Leicher explained. “Companies that are doing more analytical and functional work and are presenting less clinical data may feel they’re presenting less data. It just depends on where you sit and how you think about it.”
In the end, the question for manufacturers, as well as the FDA, is not going to be whether more or less data is needed, it’s going to be a question of the right data. As panel member Robyne Kelemen, director of regulatory affairs, biologics, at Dr. Reddy’s said, “Just as we manufacturers are becoming more experienced with the development process for biosimilars, so is the FDA. I see more standardization in their approach and the advice offered. But in these earlier stages, depending on what your company has historically done, it may feel as though more or less data is needed in certain areas.”
Industry Unity Necessary For Development Efficiency
That the industry is actually having this discussion is something at which to marvel. After all, as Leicher described, six to eight years ago, there were discussions about using structural and functional characterization as the basis for biosimilar approval. But bringing this up in discussion generally resulted in strange looks. Because the BPCIA statute stated a biosimilar had to have no clinically meaningful differences, many believed these differences could only be uncovered through large clinical trials. But Leicher is reassured by the FDA’s ongoing policy developments that emphasize best scientific approaches per development program. He expects we’ll see just as much change in development strategies in the next five to eight years as we see today compared to eight years ago.
But what has to be done to help carry the industry there? It all comes down to when a company wants to enter the market and how much money it is looking to spend. Dixit was a big advocate of embracing the bioanalytical work to reduce the amount of clinical work and the number of clinical trials. Though some members of the industry question the use of the term “fingerprint-like similarity” to describe biosimilars, he argued that being able to show fingerprint-like similarity early on would carry weight with the FDA.
Many of the larger companies approving their biosimilars have come to the FDA’s table with large amounts of data. And though some may argue these data packages have been excessive, there’s no doubt they’ve set a high bar for companies en route to the market. However, given the cost pressures today, Dixit expects something will have to give. After all, biosimilar prices can’t be lowered sufficiently if the development process doesn’t evolve beyond requiring data from hundreds of patients — the costs of which could eliminate smaller companies and competition. (A clever analogy I’ve heard describing the differences in data packages is that of a Cadillac versus a Honda. They will both get you reliably and safely from point A to point B, but for a much different cost, and one will likely have a fancier dashboard setup.)
However, Dixit emphasized the importance of more unified opinions and approaches toward biosimilar development among the different firms. While some of the bigger companies are calling for more and larger studies in biosimilar development, other companies are pushing for fewer studies. “I think we as an industry need to come together to determine, as one biologics unit, when larger studies are needed and when smaller studies can be used,” he argued. “Otherwise, we’ll keep fighting amongst ourselves.”
In the end, unity — however that may be achieved — will be necessary between larger and smaller biosimilar companies to ensure efficiency throughout development and at the regulatory level.