Lilly's Once-A-Week Insulin Demonstrates Safety, HbA1c Lowering Consistent with Daily Insulin

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The investigational once-weekly insulin efsitora alfa met the primary endpoint of HbA1c reduction noninferior to the most commonly used daily basal insulins in a pair of phase 3 studies that found the antihyperglycemic equally safe and effective in adults naïve to insulin therapy and regardless of GLP-1 mimetic use. The positive topline results of the international QWINT-2 and QWINT-4 studies were announced today by Lilly.

Lilly described the novel weekly basal insulin as a “fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain.” The once-weekly subcutaneous formulation's low peak-to-trough ratio allows more stable glucose levels over the 7-day interval, according to Lilly. The company’s QWINT clinical trial program is evaluating efsitora for adults with type 1 and type 2 diabetes.

"The results of QWINT-2 and QWINT-4 are a significant milestone for the diabetes community and demonstrate that efsitora as a weekly insulin provides blood sugar control equivalent to daily basal insulins," Jeff Emmick, MD, PhD, senior vice president, product development, Lilly, said in the press announcement. "With efsitora, we have an opportunity to provide an innovative once-weekly solution that safely achieves and maintains A1C control, reduces treatment burden of traditional daily injections and potentially improves adherence for people with diabetes."

QWINT-2 and QWINT-4 were parallel-design, open-label, treat-to-target randomized controlled trials comparing the safety and efficacy of once-weekly efsitora to daily basal insulin degludec for 52 weeks and to basal insulin glargine for 26 weeks, respectively.

In the QWINT-2 study, 928 insulin-naïve adults with T2D were randomly assigned to receive either efsitora once weekly or insulin degludec once daily; the study design also allowed investigators to assess the investigational agent’s efficacy and safety among study participants using and not using GLP-1 receptor agonists, according to Lilly.

At week 52, HbA1c reduction was 1.34% with efsitora compared to 1.26% for insulin degludec; final HbA1c levels were 6.87% and 6.95%, for the efficacy estimand, satisfying the study's primary endpoint. The study met the key secondary endpoint as well, with Lilly reporting noninferior change in HbA1c for efsitora vs degludec among users and nonusers of GLP-1 RAs. Weekly efsitora proved superior to daily insulin degludec for time in range (45 more minutes) and time in tight range (37 more minutes) with no reports of additional time in hypoglycemia (blood glucose [BG] less than 54 mg/dL).

The 26-week phase 3 QWINT-4 trial enrolled 730 adults with T2D previously treated with basal insulin glargine and at least 2 daily injections of mealtime insulin. Participants were randomly assigned to receive efsitora once weekly or insulin glargine once daily, both of which were administered with insulin lispro, according to the statement.

Lilly reported that the investigational efsitora was noninferior to traditional daily insulin glargine at week 26 for the primary endpoint of reduced HbA1c. Both insulin products reduced the measure of glycated hemoglobin by 1.07% resulting in an HbA1c of 7.12% and 7.11%, respectively, for the efficacy estimand.

The safety and tolerability profile for efsitora in both trials was favorable, Lilly said, with estimated combined rates of severe or clinically significant (BG <54 mg/dL) hypoglycemic events per patient-year of exposure of 0.58 with efsitora compared to 0.45 with insulin degludec (QWINT-2) and 6.6 with efsitora vs 5.9 with insulin glargine (QWINT-4).

Lilly launched the global phase 3 QWINT development program for efsitora in 2022. There are currently more than 4000 adults with T1D or T2D enrolled in the 5 global registration studies.

The company said it will present detailed results from QWINT-2 in October at the European Association for the Study of Diabetes Annual Meeting 2024 and also expects to release topline results from QWINT-1, QWINT-3, and QWINT-5 later this year.

Source
With once-a-week dosing, insulin efsitora alfa delivers A1c reduction and safety profile consistent with daily insulin. News release. Lilly. May 16, 2024. Accessed May 16, 2024. https://investor.lilly.com/news-releases/news-release-details/once-week-dosing-insulin-efsitora-alfa-delivers-a1c-reduction