Eli Lilly and Company (NYSE: LLY) today announced detailed results from QWINT-1, QWINT-3, and QWINT-4 Phase 3 clinical trials evaluating the safety and efficacy of investigational once-weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes who used insulin for the first time, previously used daily basal insulin, and previously used daily basal insulin and mealtime insulin, respectively. In each trial, once-weekly efsitora met the primary endpoint of non-inferior A1C reduction compared to daily basal insulin. The complete results from these studies were presented at the American Diabetes Association (ADA) 85th Scientific Sessions.
In QWINT-1, efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine at week 52 for the efficacy estimand.1,2 In the trial, efsitora was titrated to four fixed doses at four-week intervals, as needed for blood glucose control.3 In QWINT-3, efsitora reduced A1C by 0.86% compared to 0.75% for insulin degludec at week 26 for the efficacy estimand.4 In QWINT-4, efsitora reduced A1C by 1.07% compared to 1.07% for insulin glargine at week 26 for the efficacy estimand.5 In these two trials, efsitora was administered using traditional insulin dosing with adjustments based on each patient’s glucose level.
“The novel fixed-dose regimen used in QWINT-1 for once-weekly efsitora, which consisted of only four single-dose titration options, has the potential to facilitate and simplify insulin therapy, reducing the hesitation often associated with starting insulin to treat type 2 diabetes,” said Dr. Julio Rosenstock, senior scientific advisor for Velocity Clinical Research at Medical City Dallas, clinical professor of medicine, University of Texas Southwestern Medical Center, and lead trial investigator for QWINT-1. “A simpler, once-weekly regimen with efsitora may help people with type 2 diabetes initiate and manage insulin therapy with the goal of improving blood sugar levels. Across all QWINT trials, the results showed that once-weekly efsitora controlled glucose as effectively as the most popular once-daily basal insulins.”
QWINT-1 Primary Endpoint
| Efficacy Estimand | Treatment-Regimen Estimand6 | |
| Primary Endpoint – A1C Reduction (Resulting A1C) at Week 52 | ||
| Efsitora | -1.31% (6.92%) | -1.19% (7.05%) |
| Glargine | -1.27% (6.96%) | -1.16% (7.08%) |
QWINT-3 Primary and Key Secondary Endpoints
| Efficacy Estimand | Treatment-Regimen Estimand | |
| Primary Endpoint – A1C Reduction (Resulting A1C) at Week 26 | ||
| Efsitora | -0.86% (6.93%) | -0.81% (6.99%) |
| Degludec | -0.75% (7.03%) | -0.72% (7.08%) |
| Key Secondary Endpoint – Rates of Clinically Significant or Severe Nocturnal Hypoglycemic Events Per Patient-Year of Exposure up to Week 787,8 | ||
| Efsitora | 0.11 | |
| Degludec | 0.10 | |
| Key Secondary Endpoint – Percent Time in Range (70-180 mg/dL) During the 4 Weeks Prior to Week 26 | ||
| Efsitora | 62.8% | 61.4% |
| Degludec | 61.3% | 61.0% |
QWINT-4 Primary and Key Secondary Endpoints
| Efficacy Estimand | Treatment-Regimen Estimand | |
| Primary Endpoint – A1C Reduction (Resulting A1C) at Week 26 | ||
| Efsitora | -1.07% (7.12%) | -1.01% (7.17%) |
| Glargine | -1.07% (7.11%) | -1.00% (7.18%) |
| Key Secondary Endpoint – Participants Achieving A1C <7% at Week 26 Without Nocturnal Hypoglycemia | ||
| Efsitora | 39.5% | 38.6% |
| Glargine | 36.6% | 35.9% |
| Key Secondary Endpoint – Rates of Clinically Significant or Severe Nocturnal Hypoglycemic Events Per Patient-Year of Exposure up to Week 26 | ||
| Efsitora | 0.67 | |
| Glargine | 1.00 | |
“Building on Lilly’s legacy of innovation in insulin therapy, once-weekly efsitora may offer a significant advancement for people with type 2 diabetes who need insulin by eliminating over 300 injections per year,” said Jeff Emmick, MD, Ph.D., senior vice president of product development at Lilly. “These results reinforce the potential for once-weekly efsitora to help reduce the overall burden of insulin therapy through a simplified treatment approach. We look forward to working with regulatory agencies to bring this innovation to patients around the world.”
Across the three trials, efsitora demonstrated an overall safety profile similar to two of the most commonly used daily basal insulin therapies for the treatment of type 2 diabetes. In QWINT-1, efsitora resulted in approximately 40% fewer hypoglycemic events compared to insulin glargine, with estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure of 0.50 with efsitora vs. 0.88 with insulin glargine at 52 weeks. In QWINT-3, these rates were 0.84 with efsitora vs. 0.74 with insulin degludec at 78 weeks. In QWINT-4, rates of estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure were 6.6 with efsitora vs. 5.9 with insulin glargine at 26 weeks.
Lilly plans to submit efsitora for the treatment of adults with type 2 diabetes to global regulatory agencies by the end of this year.
