Last week the U.S. Food and Drug Administration approved an interchangeable biosimilar to insulin glargine, an approval notable because it is the first approved interchangeable biosimilar product.  The product is Semglee (insulin glargine-yfgn), produced by Mylan Pharmaceuticals, Inc., and under this approval, it is interchangeable with Lantus (insulin glargine) made by Sanofi.

The approval was based on the provisions of the Biological Price Competition and Innovation Act of 2009 (BPCIA), enacted with the Affordable Care Act (commonly known as "Obamacare") codified at 42 U.S.C. § 262 et seq.  Subsection (k) relates to the standards for biosimilarity; the FDA (and the statute itself) distinguish between biosimilarity and interchangeability inter alia by applying a heightened standard for interchangeability.  Specifically, the statute requires that an interchangeable product is biosimilar and can be expected to produce the same clinical result as the reference product in any given patient; and that for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.  42 U.S.C. §§ 262(I)(3) and 262(k)(4).

Insulins are in a unique class of biologic drugs that, for historical reasons, were approved under the Food, Drug, and Cosmetics Act (codified at 21 U.S.C. § 301 et seq.).  The BPCIA provided a sunset date of March 23, 2020 for such approvals; the FDA finalized rulemaking on this change on February 20, 2020.  Under the revised rule, any protein having a defined amino acid sequence of 40 amino acids or longer falls within the statutory definition of the term "protein" and hence is considered to be a "biological product" as defined by the BPCIA (42 U.S.C. § 262(I)).

Semglee (insulin glargine-yfgn) was approved for treatment of Type 1 diabetes (i.e., the juvenile form) diabetes as well as Type 2 diabetes (i.e., the adult-onset form).  The FDA announcement prophesied that "[a]pproval of these insulin products can provide patients with additional safe, high-quality and potentially cost-effective options for treating diabetes."  Acting FDA Commissioner Janet Woodcock, M.D. stated that this approval has "the potential to greatly reduce healthcare costs" (a sentiment that, if true, would be a boon to the sometimes overheated debate over drug prices having insulin as a poster child; see, e.g., "Insulin's Out-Of-Pocket Cost Burden To Diabetic Patients Continues To Rise Despite Reduced Net Costs To PBMs").  This is clearly significant to the over 34 million individuals in the U.S. diagnosed with diabetes.  The Acting Commissioner also hailed FDA's "longstanding commitment to support a competitive marketplace for biological products and ultimately empowers patients by helping to increase access to safe, effective and high-quality medications at potentially lower cost."

As set forth in the FDA's announcement, Semglee (insulin glargine-yfgn) was approved for dispensing in 10 mL vials and 3 mL pens for administration twice daily.

It is not surprising, perhaps, that insulin, a biologically derived drug known since the 1930's would, in its modern embodiments, be the first molecule to satisfy FDA guidance on the standards for interchangeability (see "FDA Issues Final Guidance Regarding Biosimilar Interchangeability").  While there has been some concern with the perceived slow pace of biosimilar uptake by physicians and patients (see "FDA Issues Plan for Further Facilitating Biosimilar Development"), one of the benefits of interchangeability is that physicians' input (and approval) is not needed and can be implemented at the pharmacy level.  While this pathway for FDA approval is less advantageous than with small molecule drugs (which are typically administered by the patient herself as a pill, as opposed to biologic drugs which are infused by a physician or other healthcare provider), the FDA's exultations regarding Semglee's approval are well-taken as an indication not only that the FDA is willing (under the appropriate circumstances) to approve an interchangeable biological product but also as a teaching opportunity for other biosimilar drug makers on how to successfully navigate the FDA's pathway to interchangeability (desirable in addition for the exclusivity provisions only available to interchangeable biosimilar drugs).  Whether a dam-burst of interchangeable biosimilar drug products will now arise of course remains to be seen.