Lilly wins FDA approval for second interchangeable insulin biosimilar

The emergence of interchangeable biosimilars since the pathway opened up has been slow. But the FDA on Thursday approved the fourth interchangeable biosimilar, which is also the second interchangeable biosimilar insulin product.

Eli Lilly’s Rezvoglar (insulin glargine-aglr), which converted to an interchangeable after an earlier biosimilar approval in December 2021, follows Viatris’ Semglee in seeking out a niche to compete with Sanofi’s blockbuster Lantus (insulin glargine).

And while the FDA and biosimilar experts have said that interchangeables will drive price competition, Viatris launched both a high- and lower-priced version of Semglee to deal with the market dynamics, and Lilly did not respond to a request for comment on the price of Rezvoglar moving forward.

These interchangeable designations mean Semglee and Rezvoglar may be substituted at the pharmacy level for Lantus, without a doctor’s prescription, and as long as the state pharmacy law permits the switch.

The FDA has also been more permissive of approving interchangeable biosimilars, which come with 12 months of exclusivity, without meeting all of the stipulations that the agency initially laid out.

In the case of Rezvoglar, an FDA spokesperson told Endpoints News that no new clinical data needed to be submitted to support the interchangeable tag. “Neither a comparative clinical immunogenicity study nor a switching study was needed to support licensure,” the spokesperson said.

Current “state-of-the-art analytical tools” used to evaluate the quality attributes for insulin can allow for comparisons “thorough enough that a particular proposed biosimilar insulin product that is ‘highly similar’ to its reference product generally would be expected, like the reference product, to have minimal or no risk of clinical impact from immunogenicity,” the FDA spokesperson added, noting:

Based on the contents of the 351(k) BLA, including a comprehensive and robust analytical assessment that compared the structural and functional characteristics of Rezvoglar to Lantus (insulin glargine), human pharmacokinetic and pharmacodynamic data that compared systemic exposure and glucose response rates, and a clinical immunogenicity assessment justifying why a comparative clinical immunogenicity study was not needed, FDA determined that neither a clinical immunogenicity study nor a switching study were needed to support licensure of Rezvoglar as interchangeable to Lantus. In other words, no additional clinical studies were needed to support approving Rezvoglar as interchangeable with Lantus beyond those needed to support approving Rezvoglar as biosimilar to Lantus.  The information submitted demonstrated that Rezvoglar (insulin glargine-aglr) can be expected to produce the same clinical result as Lantus in any given patient and that the risk in terms of safety or diminished efficacy of alternating or switching between use of Rezvoglar (insulin glargine-aglr) and Lantus is not greater than the risk of using Lantus without such alternation or switch.

Viatris’ Semglee similarly won approval as an interchangeable to Lantus even though FDA also didn’t require a clinical immunogenicity study comparing Semglee to Lantus.

Similarly, biosimilar company Coherus BioSciences won approval in August for Cimerli (ranibizumab-eqrn), an interchangeable biosimilar to Roche’s injection Lucentis, without running a switching study to see how patients fared after moving from Lucentis to the interchangeable. The agency said in this case it:

believes that the risk of a clinically impactful immunogenic response from systemic anti-drug antibodies and intraocular inflammation when alternating or switching between Cimerli and Lucentis is low. A switching study that compares immunogenicity and pharmacokinetics (PK) and/or pharmacodynamics (PD) will not be informative to demonstrate that the risk in terms of safety or diminished efficacy of alternating or switching between Cimerli and Lucentis is not greater than the risk of using Lucentis without such alternation or switch.

Jacqueline Corrigan-Curay

The future for interchangeable biosimilars will likely hit more insulins and AbbVie’s blockbuster Humira next year. In the case of Humira, Boehringer Ingelheim is ready to launch its adalimumab interchangeable, and several others may be forthcoming next year.

Over the next five years, the FDA’s biosimilar leaders are pushing forward with a sharper focus on interchangeables too.

“What we’re going to really focus on in BsUFA III is how to develop an interchangeable product,” Jacqueline Corrigan-Curay, who’s also leading the search for a new director of FDA’s Office of Generic Drugs, explained at a recent industry conference.

Editor’s note: Updated with comment from the FDA.

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