Merck Wins Tentative FDA Approval of Follow-on Insulin Glargine

The FDA has granted Merck’s insulin glargine (Lusduna Nexvue) tentative approval. Merck says that its follow-on basal insulin has met all required regulatory standards of clinical and nonclinical safety, efficacy, and quality for follow-on biologics. “The tentative approval of Lusduna Nexvue is an important milestone, bringing us closer to offering this medicine to patients,” said Sam Engel, MD, associate vice president of Merck clinical research, diabetes, endocrinology and women’s health.

The FDA will not issue its final approval, however, until patent infringement litigation, brought by Sanofi, has concluded. Sanofi, maker of Lantus, contends that Merck has infringed upon its patents for insulin glargine, and its suit triggered an automatic stay on the FDA’s final approval of up to 30 months (unless the US District Court hearing the case rules in favor of Merck, in which case final approval may proceed immediately).

After litigation has concluded, Lusduna will not only compete with Lantus in the US market, but also with Boehringer Ingelheim (BI)'s Basaglar, the first follow-on insulin glargine product approved by the FDA. In its first quarter on the market, Basaglar earned $22 million in US sales, and $46 million worldwide. BI received approval for the follow-on insulin glargine in late 2015, but Basaglar did not become available in the US marketplace until the following year, when BI reached a settlement with Sanofi in its own litigation.

Merck, like BI, will have to address patent infringement claims under the Hatch-Waxman Act, which governs the generic drug approval process, rather than under the Biologics Price Competition and Innovation Act and the so-called “patent dance.” In the United States, innovator insulins are regulated as drugs, rather than as biologic products that fall under the Public Health Service (PHS) Act. Products that are approved and regulated under the PHS Act must, according to the act’s Section 351, be categorized as blood-derived products, vaccines, in vivo diagnostic allergenic products, immunoglobulin products, products containing cells or microorganisms, and most protein products. That leaves hormone products like insulin (as well as glucagon and human growth hormone), to be regulated under the Food, Drug, and Cosmetic Act.

The FDA’s approach to the approval and regulation of insulins stands in contrast to the European Medicines Agency’s approach, which treats such products—and low-molecular-weight heparin products like enoxaparin—as biosimilars. Lusduna was issued a marketing authorization as a biosimilar in the European Union in April of this year, where it is undergoing additional monitoring.

Follow-on versions of insulin glargine are widely expected to generate cost savings in the treatment of diabetes, but experts point out that the regulatory pathway for such drugs requires a wealth of clinical trial data, and that the design and development costs for delivery devices also pose a substantial cost challenge. According to some estimates, it could be 2018 before enough follow-on insulin glargine products are competing with Lantus in order to drive significant cost-savings for both payers and patients.