By Anna Rose Welch, Director, Cell & Gene Collaborative
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In the regulatory sphere, there have been many exciting discussions and evolutions proposed over the past year. But one change is actually poised to happen come March 23, 2020. Ninety products that were previously regulated as drugs under the Food, Drug, & Cosmetic Act (FD&C Act) — including growth hormones and insulins — will be deemed biologics and regulated under the Public Health Service (PHS Act). This means that branded insulins and growth hormones currently on the U.S. market will no longer be considered drugs, but biologics. Any copies of those branded products that are developed (and there are some in the works) will then be submitted to the FDA and reviewed in accordance with the biosimilar pathway. Moving forward, novel insulins/growth hormones, etc., will be submitted to the FDA via the 351(a) pathway for novel biologic products.
In the regulatory sphere, and for companies planning to submit biosimilar applications, this transition has obviously been watched closely. Not only does it raise questions about what might change on the regulatory requirements side of things, but it also raises additional commercialization questions. In the U.S., there are currently no biosimilar products delivered to patients via the pharmacy. But insulins are; so, once insulins have biosimilar competition, interchangeability (pharmacy-level substitution) becomes a front and center consideration. (And, given the FDA’s latest guidance on clinical immunogenicity considerations for insulins, we may actually be facing a future of interchangeable insulins, fingers crossed.)
In the first part of this two-part series, I addressed a number of these considerations, thanks to the information relayed during a panel on the upcoming transition at September’s DIA Biosimilar Conference. The FDA’s Eva Temkin emphasized that this change will only require minimal labeling and CMC changes for transition products, and Sundar Ramanan of Biocon dug into the science of insulin molecules, arguing in favor of more flexible clinical requirements for insulin biosimilarity and interchangeability approvals. Judging from its recent guidance, the FDA is in agreement with much of what Ramanan and other industry members have been saying.
But one voice that has been quiet during all of these conversations about the transition has been that of the patient. Obviously, from a business and regulatory affairs perspective, this transition turns heads. On the patient side, however, what is the awareness to such a change, and in what ways could it impact patients? Thankfully, I got a few answers from Marjana Marinac, the senior director of regulatory affairs, drugs and biologics for the Juvenile Diabetes Research Foundation (JDRF), who also participated on the DIA panel with Temkin and Ramanan. In this article, Marinac shares the diabetes community’s perspective on this change and how the industry can better engage and educate patients about the future presence of insulin biosimilars.
Where The Regulatory World And Patient Experience Diverge
A few weeks ago, I had a great conversation with one biosimilar stakeholder about their expectations for the market. What struck me, in particular, was their optimism and confidence it wouldn’t be as hard to get buy-in on biosimilars from certain stakeholders as some seem to be anticipating. Of course, the responses and barriers can differ drastically depending on the stakeholder. But it was refreshing to hear there was a general level of comfort at the thought of greater biosimilar market presence.
The biosimilar industry loves to pose the “what ifs” and throw in some “ands” and “buts,” (which are all important to consider). From what I hear though, there isn’t anxiety (nor is it expected) in the patient community about March 24, 2020 once insulins become known as biologics/biosimilars. There are rightfully concerns about the regulatory “dead zone” for new and biosimilar insulins created by this transition. However, the FDA’s Temkin reassured that it’s highly unlikely this transition will create access issues, nor does this regulatory change alter or affect the drug itself. So, from a safety and efficacy standpoint, there is no need to be concerned on the patient or physician side.
Marinac confirmed these claims, saying that she doesn’t anticipate patients suddenly won’t be able to receive their insulins or they’ll be unable to recognize the products they’re currently taking come March. In fact, she admitted that the community as a whole hasn’t heard much about this transition. So, while it may be relatively monumental in the industry to redefine a drug as a biologic, Marinac emphasized, “I just don’t think patients today are thinking about whether their insulin is a drug or a biologic,” she said. “Rather, patients today recognize their medicines by their brand names.”
For instance, patients may be somewhat familiar with the nonproprietary names for insulin — insulin lispro, aspart, glargine, detemir, or degludec. But that knowledge may not always carry over to knowing how and when to administer the insulin or whether it’s long- or short-acting. This will only become more complex as biosimilars are approved. The community has also just started to see authorized generics, which have also added confusion as payers begin adding them to formularies. One example Marinac shared was how a community member expressed confusion upon learning that her insurance changed her prescription from the brand Humalog to insulin lispro — which is just the nonproprietary name of Humalog.
“There’s all this terminology as part of the transition, and I think for those in the insulin community, not only would patients benefit from this education, but also the physicians, endocrinologists, pharmacists, and insurers to ensure that these formulary changes are relayed accurately,” she said.
It’s also critical to look beyond these stakeholders, given the pressures the disease places on patients’ caretakers. As she shared, this disease requires a lot from both the patient and their family members or caretakers. “I hear a lot of people say they know more than their doctor about how to manage their disease,” Marinac added. For some, the doctor provides refills of their insulin or is a support system when treatment isn’t working effectively.”
Overall, I appreciated Marinac’s practical advice for the industry, which is critical given that we tend to operate within the confines of our regulatory, scientific, and legalese-heavy careers. It can be hard to step back from these to look at how those outside of these spheres may receive or perceive (or not entirely perceive) changes like this regulatory transition.
If anything, Marinac — a type 1 diabetes patient herself — said that patients will not be looking at or thinking about the clinical performance of their insulins in the same way that regulators and manufacturers are. “There are differences between certain regulatory requirements, and what patients with this disease have to do daily,” she pointed out. For instance, patients do not change their dosing regimens based on A1C levels. Rather, these decisions are made based on blood sugar measurements which are gleaned in a variety of ways. The clinical effect of insulin can also vary differently depending on the time of day for many different reasons. “Even though we may be taking the same insulin every day, it doesn’t work the same every day,” Marinac added.
The complexity of managing this disease makes it all the more important to be in-tune with the differences in language that exist between the patient population and the medical/regulatory spheres. If there was one takeaway that was loud and clear following Marinac’s presentation and that of several other patients throughout the DIA conference, it’s that the language we use to describe these treatments matters. Seeing as diabetes is such a complex disease to manage for both patients and their caretakers, it becomes even more important to see unified messaging about the biosimilars and biologics that will appear on the market in the future. If patients were to see the introduction of new insulins or biosimilar insulins as a hurdle to overcome, it will only make the treatment of this complicated disease even more trying for patients.
For companies and stakeholders striving to educate patients in light of this transition, Marinac advised that, first and foremost, we all strive for consistency in educational materials. In fact, one of my favorite best practices from the DIA conference came from Marinac: “Let’s not make this transition a problem,” she said. “It’s about preparing the field and the community for what’s to come and creating messaging that is appropriate for each stakeholder and consistent with the other voices engaging in this area.”