3 Lessons From The GPhA Biosimilars Council Conference
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
I recently made my way to North Bethesda, MD, for the inaugural Leading on Biosimilars Conference, hosted by The GPhA Biosimilars Council. During the two-day conference, I heard insights from the FDA’s Janet Woodcock and Steven Kozlowski; Sanford Bernstein Analyst, Ronny Gal; Elizabeth Jex of the Federal Trade Commission; and numerous executives from high-profile biosimilar companies and payers, including Sandoz, Mylan, and Express Scripts. This conference touched upon many of the topics one would expect, including reimbursement, interchangeability, naming, the global markets, and IP challenges. But I felt three overarching topics were particularly worthy of being singled out.
- Biosimilars Fight For Credibility
As Bert Liang, chair of the Biosimilars Council and CEO of Pfenex, discussed in his opening remarks, biosimilars are proof of how innovative the pharmaceutical industry has become. Technology has vastly improved, leading to a clearer understanding and more sophisticated analysis of large molecules. But in addition to technological advances, we’ve also seen regulatory innovation in the form of abbreviated pathways.
The pride in the work being done in the biosimilar space and the urgency to make sure the market gets off on solid footing was a powerful undercurrent running throughout the entire conference. As GPhA President and CEO Chip Davis described, “The generics industry today is anything but boring.” The news during the conference of Apotex’s legal triumph over Amgen and Biogen’s EU release of Flixabi certainly validated this statement.
There are clear parallels between the generics industry’s struggles to gain credibility against originators in the ’80s and the fear mongering biosimilars face today from brand companies. The U.S. is still awaiting final policies on naming, labeling, and interchangeability, all of which will impact the rate of uptake of biosimilars. As such, it is immensely important for biosimilar companies to get involved in industry organizations to be sure their voices are part of these critical, market-shaping negotiations. As Liang said in his opening speech, “It is our charge to make this industry and our work in it understood by all the stakeholders.”
- Makers Must Learn To Communicate Complex Science
I’ve discussed the biosimilar development triangle in past articles, and it was referenced in several of the conference panels. Analytics makes up the large base of the biosimilar triangle, with clinical trials being the small tip of the triangle. This differs from a novel biologic, which emphasizes clinical trials. As Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research (CDER), discussed, the concepts of biosimilarity and the use of clinical trials as proof of molecular similarity are difficult to grasp. Comparative analytics proving similarity to a reference molecule are even harder to understand. “People’s eyes glaze over in advanced analytical science discussions,” Woodcock said. (And this isn’t just restricted to patients and physicians; a number of industry experts I spoke to at this conference also expressed difficulty following the panel on comparative analytics.) But because of advances in analytical science, the FDA is learning even more about the science behind innovator drugs, and in turn, their biosimilars. “These biologics weren’t exactly what we thought they were when we first approved them. They had ‘refinements’ we didn’t know about,” explained Woodcock. As such, the analytical science is proving to be a more insightful tool for understanding biosimilars than the clinical trials so long emphasized by physicians and clinicians.
At every conference, AdCom meeting, and congressional hearing, we leave hearing the word “education” ringing in our ears. This conference was no exception. While companies are able to talk amongst themselves about sophisticated concepts like totality of evidence and biosimilarity, these terms and the science behind them are too complicated to present to prescribers and patients. “The patient groups are requesting a lot of information, and that is a burden that will need to be carried by the early arrivers to the biosimilar market,” said Woodcock. As fear mongering efforts threaten to discredit biosimilars as safe and effective treatments, it might seem patients and doctors need to know solely about what a biosimilar is. But what biosimilar makers and organizations really need to do at this point is take a step back to the reference biologic. It’s important to emphasize the molecular differences occurring in a biosimilar are not unique to biosimilars, but are also seen in the reference products themselves. These small changes from molecule to molecule are characteristic of biologic treatments in general; they are not just a biosimilar problem. This is one key point all stakeholders must understand.
- Quantity Of Data Does Not Mean Quality
Naming and labeling protocol garnered a lot of attention at this conference. Both FDA officials Woodcock and Kozlowski homed in on the specifics of the current draft guidances for both topics. (Interchangeability guidance, on the other hand, was mentioned only once, and very briefly, by Woodcock, who reiterated the agency’s goal of releasing it by the end of this year.) The FDA seems determined to require a four-letter suffix for biosimilars, as well as to include a biosimilarity statement on the label. But a potential win for biosimilars is the fact labels can contain the reference product’s data, rather than the biosimilar’s comparative data. After all, the label is supposed to contain the data that is essential for use.
However, physicians — the main gateway to uptake of these biosimilars — are pushing for this comparative data. These days, the pharma industry has been increasingly focused on transparency, especially of clinical data. As such, the question posed to physicians is, “Do you want to see the data?” However, perhaps a better question to ask is, “Do you understand this data?” CMO of Pfenex, Hubert Chen, who completed medical school and is board certified in internal medicine, and endocrinology, diabetes, and metabolism, admitted, “I never read a drug label until I came into the industry.”
When it comes to data, the biosimilar industry ultimately needs to be careful it doesn’t fall prey to the notion that more is better. Take interchangeability, for instance. This status is not supposed to equate to a measure of the biosimilar’s quality. Rather, a biosimilar deemed interchangeable will have submitted a different, likely larger data package. However, the amount of data required needs to be manageable, Liang argued. If the FDA requires even as much as four different studies, this would not only defeat the purpose of the abbreviated pathway for biosimilars, but it would also eliminate the cost-effectiveness of developing a competitive biosimilar. And an even bigger threat facing biosimilars once an interchangeability designation is granted is that those lacking an interchangeability designation (and the data that comes with it) could appear to be inferior products.
In fact, placing too many eggs in the clinical data basket could also interfere with regulatory innovation in the U.S. For instance, biosimilar development could be made more efficient by turning to truncated clinical studies emphasizing pharmacokinetic and pharmacodynamic (PK/PD) assessments in healthy patients and an immunogenicity assessment, also performed on healthy patients. (The use of this abbreviated structure ultimately depends on the molecule, and how much is known about the clinical profile of the reference molecule in healthy subjects, as well as dosing requirements.) But we likely still have a ways to go before this becomes the norm for a majority of biosimilar candidates.
Perhaps one of the more memorable, if not controversial, opinions expressed was that these truncated studies could help biosimilar players “win the battle” and get to market more quickly. But, because payer pharmacy and therapeutic (PNT) committees determining a formulary are looking at the totality of data, “biosimilars relying on these abbreviated trials would ultimately lose the war.”