Lilly closes distance on Novo with another clutch of positive data on once-weekly insulin prospect

On the heels of an FDA rejection for its chief rival Novo Nordisk, Eli Lilly is gaining ground in the race to bring a once-weekly insulin to the U.S.

Early Thursday, Lilly unveiled positive top-line results from a pair of phase 3 trials—QWINT-1 and QWINT-3—assessing its once-a-week basal insulin candidate called efsitora alfa.

QWINT-1 and QWINT-3, which are part of a larger five-trial program for the drug, looked at efsitora's ability to lower the A1C measure of blood sugar in patients with Type 2 diabetes who were using basal insulin for the first time and in those who switched from daily insulin injections, respectively.

Both studies met their primary endpoints, with efsitora achieving noninferior A1C reductions when pitted against two common daily insulins, Lilly said.

Peeling back the numbers on QWINT-1, efsitora at 52 weeks cut patients’ A1C by an average of 1.31% compared to 1.27% in patients on daily insulin glargine, yielding overall A1C averages of 6.92% and 6.96%, respectively. The study saw efsitora titrated across four fixed doses at four-week intervals, as needed for blood glucose control, Lilly said.

The company figures fixed-dose regimens could make it easier for people with diabetes to start and manage insulin therapy.

Meanwhile, in QWINT-3—which randomized patients two-to-one to receive either efsitora or daily insulin degludec—Lilly’s once-a-week prospect lowered A1C by an average of 0.86% at the study’s 26-week mark versus 0.75% in the degludec cohort. That reduction yielded total A1C averages of 6.93% and 7.03% for patients treated with efsitora and insulin degludec, respectively.

Overall safety and tolerability of efsitora was largely on par with daily basal insulins, Lilly added. In QWINT-1, rates of severe or clinically significant hypoglycemic events were roughly 40% lower for patients in the efsitora arm than for those who received insulin glargine. As for QWINT-3, estimated rates of clinically significant low blood glucose events per patient-year of exposure from weeks 0-78 were 0.84 with efsitora vs. 0.74 with insulin degludec. 

With the latest data, Lilly continues to build the case for its once-a-week insulin product. The data drop follows prior positive news in May, when Lilly reported that efsitora met similar A1C noninferiority endpoints in the QWINT-2 and QWINT-4 studies.

Lilly designed QWINT-2 to assess whether the use of GLP-1 medicines like Mounjaro or Novo’s Ozempic could weigh on efsitora’s efficacy, but the once-weekly-product demonstrated noninferiority compared to daily dosing in that trial’s GLP-1 subgroup.

QWINT-4, on the other hand, looked at the efficacy of efsitora in Type 2 diabetes patients who’d previously been treated with basal insulin and who needed at least two injections of mealtime insulin each day.

As Lilly starts to round out its clinical quintet for efsitora, the company says it plans to present detailed results from QWINT-2 and QWINT-5 at the annual meeting of the European Association for the Study of Diabetes later this month.

While Novo has remained squarely in the lead with its own once-weekly insulin icodec—approved as Awiqli in Europe, Canada, Japan and Australia—the company suffered a recent setback in the U.S. when the FDA rejected the drug over manufacturing questions and issues tied to the product’s potential Type 1 diabetes indication.

In July, Novo said it didn’t expect to resolve the regulatory issues surrounding insulin icodec before the year is out.