How Califf As FDA Commissioner Could Benefit Biosimilar Market

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

There are still many key decisions that the FDA needs to make when it comes to biosimilars. Why should we feel optimistic that Califf is the man to make them?

Last week, my colleague Ed Miseta wrote a column for Biosimilar Development’s sister publication Clinical Leader, in which he posed the question “Should a clinical mastermind run the FDA?” He is referring to what has had the industry expressing both excitement and concern: President Obama’s recent nomination of the FDA’s current Deputy Commissioner Robert M. Califf to be the next FDA commissioner. Despite Califf’s sterling reputation as a clinical researcher credited with heading the renowned clinical research center at Duke University, his experience as a consultant to many Big Pharma clients and the $215,000 in consulting fees he received from 2009 to early 2015 has raised some concerns. While Califf has been donating his consulting fees to nonprofits, many worry his past relationships with pharma companies could be a conflict of interest when he’s at the helm of the FDA and responsible for making industry-changing regulatory decisions.

In his article, Miseta questions whether the drug development process would be easier if there was a clinical researcher heading the FDA. Since my daily existence now consists of living and breathing all things biosimilars, I would like to push his question toward that emerging market. Should we feel hesitant about Califf’s relationship with Big Pharma, especially during a time when so many key decisions about biosimilars still have to be made?

Biologics Vs. Biosimilar Makers: Where Do Califf’s Interests Lie?

Both The New York Times and The Wall Street Journal report that Califf was contracted as a consultant by Merck, GSK, Johnson & Johnson, Novartis, Eli Lilly, Roche, Sanofi, and Amgen. When I began hearing the industry’s concern about Califf’s Big Pharma ties, my first thought was, how many of those ties were with reference makers facing patent expirations as opposed to biosimilar makers? While, of course, all of these companies are top players in the industry with many high-profile brand name treatments, luckily, four of these companies are also investing in biosimilar development: Novartis (or rather, its company Sandoz), Merck, Eli Lilly, and Amgen. This fact was reassuring to me, given the number of big decisions on interchangeability, extrapolation, and labeling the FDA still has yet to make. In fact, just this week, National Health Services (NHS) of England released a guidance forbidding substitution at the pharmacy without a doctor’s permission, which, frankly, is a blow to biosimilar makers. Therefore, the industry’s concern about Califf’s former industry ties were some of my own concerns, especially as news of this nomination coincided with the director of the Center for Drug Evaluation and Research (CDER) Janet Woodcock’s speech on the agency’s difficulty in ruling on interchangeability.

But I’m also reassured for a different reason. As we’re already seeing with Amgen, some pharma companies are beginning to forge identities as both reference and biosimilar makers. I picture these companies currently juggling both biologics and biosimilars as enterprise versions of Jekyll & Hyde. As this market takes shape, it might seem like the two sides of the same company — biologics and biosimilars — are fighting against each other. Companies like Amgen will need to brace for hits to either side of its business as the FDA makes its biosimilar decisions. I’ve said it before, and I’ll say it again: it’s no secret the industry is currently polarized when it comes to brand and biosimilar makers. While Amgen is the only one in the list that is deeply enmeshed in both sides — having both biologics losing patent protection and biosimilars in its portfolio — I doubt that will always be the case. In the end, it might not matter how close of ties a company had with Califf if it’s the manufacturer of both soon-to-be-expired reference drugs and biosimilars. (The reference-drugmaker-gone-biosimilar-maker is a topic I expect I’ll address in a future article. I’ve been pondering this a lot more since reading a recent article by Simon King in FirstWord Pharma that questions how Amgen will handle the fact that it’s “straddling both sides of the biosimilar fence.”)  

What Can Califf Do For The Biosimilar Market?

But looking beyond Califf’s industry ties, I also think that Miseta’s question about his impact on drug development — especially in the clinical space — is an important one to consider in relation to biosimilars. Seeing as these treatments need to go through the clinical trial process before being approved, having a clinical trials mastermind manning the FDA could be quite beneficial as biosimilar makers go about proving similarity. And who better to be there supervising this than Califf who, according to The NYT, has “come up with groundbreaking trial designs?” Cleveland Clinic cardiologist Dr. Steven Nissen told The NYT, “His integrity in scientific matters is impeccable, and his innovation in clinical trial design is legendary.” It’s hard to ignore someone who is capable of legendary things — especially when being faced with the launch of a new market that will be shaking up and perhaps redefining the U.S. biopharma space and its players.

In particular, Califf, with his impressive clinical background, could be the man to help answer some of the concerns arising over substituting biosimilars for reference biologics. There are a number of questions being raised in the industry about documenting a biosimilar’s similarity, and it seems these questions will best be answered within clinical trials. The agenda for the BioPharma Mexico 2015 conference just crossed my desk, and it will feature a keynote panel questioning whether it’s “realistic to require more clinical data from biocomparable products already in the market.” One of the questions this panel plans to address is how necessary it is to have Phase 3 clinical studies for biosimilars.

Similarly, in Woodcock’s speech last week, she addressed the fact that biologics and biosimilars differ from lot to lot. Naturally, biosimilars of the same reference drug from different manufacturers will also differ slightly. The FDA is currently attempting to determine, using analytical chemistry and statistics, the extent to which these variations will matter when being taken by patients. This concern, however, is not singular to the U.S. The Pharmaceutical Benefits Advisory Committee (PBAC) recently ruled in favor of biosimilar substitution in Australia. However, questions and concerns still persist about whether switching patients to different biosimilar medicines from month-to-month will cause any adverse effects. In fact, this is one of the existing concerns the Pharmaceutical Society of Australia (PSA) mentioned in its recent position statement on biosimilar medicines. It will not be feasible to run clinical trials for every new batch of a biosimilar, of course. But it seems that the impact of switching could and should be determined through clinical trials — and who best to help come up with ways to do this than Califf who is capable of “legendary” clinical trial innovations?

Biosimilars: Pharma’s Much-Needed Source Of Creative Destruction

Overall, I feel Califf brings some important qualities to the table at an important time for biosimilars. In a 2014 presentation before biomedical researchers, lawyers, and other industry members, Califf discussed the need for accelerated biomedical innovation, pointing out that one of the key things standing in the way of disruptive innovation is regulation. Naturally, this would raise some eyebrows, seeing as this is the man slated to take over what is considered the “gold standard” of regulatory agencies. Of course, Califf isn’t arguing in favor of eliminating regulation or the FDA; rather, it seems he’s interested in redefining regulation. In a TIME article in February, Califf was cited claiming, “The greatest progress almost certainly will be made by breaking out of insular knowledge bases and collaborating across the different sectors (industry, academia, and government in particular). [There is] a tension which cannot be avoided between regulating an industry and creating the conditions where the industry can thrive, and the FDA’s got to do both.” In fact, he seems to defend his relationships with pharma companies, saying it would be “useful to have someone [leading the FDA] who understands how companies operate because you’re interacting with them all the time.”

This quote certainly contributes to industry concerns that he could be swayed in his decision making. But I was able to overlook this because of Califf’s decision to cite the Austrian-American economist Joseph Schumpeter’s ideas on creative destruction in his presentation: “New does not grow out of the old but appears alongside of it and eliminates it competitively.” This quote seems to fit the current industry well, considering the struggles (and fears) of biologics and biosimilar makers to assert the values of their separate products. I feel Califf’s interests in disruptive innovation and creative destruction bodes well, rather than ill, for the biosimilar market. For such a conservative industry, he seems to understand the need to keep moving forward.

We’ve been the industry of “me-too” drugs, and we’ve tailed behind the European market in terms of biosimilars for years. In the meantime, technology and science have advanced, leading to the development of drugs capable of treating diseases more effectively than once thought possible. But our industry can’t continue to grow and innovate without some kind of competition, and biosimilars, which are based off of the old, are going to require biologics makers to find new ways (and new biologic products) to assert the overall value of biologics for patients. Though my arguments that biosimilars do indeed fit into the innovation paradigm has sparked some lively debate among our readers, I’m still inclined to apply Califf’s and Schumpeter’s ideas to the biosimilar market. If Califf's ideas for disruptive innovation hold true in his leadership, perhaps the developing biosimilar market will be in good hands with him at the FDA’s helm.