In a fixed dose study, once weekly insulin efsitora alfa leads to HbA1C reduction similar to daily insulin

• In the phase 3 study, QWINT-1, efsitora was administered via four fixed doses once weekly in a single-use autoinjector in people with type 2 diabetes using basal insulin for the first time
• In a second phase 3 study, QWINT-3, efsitora also delivered non-inferior HbA1C reduction compared to daily insulin in people with type 2 diabetes switching from daily basal injections

BASINGSTOKE, 5th September, 2024 – Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the QWINT-1 and QWINT-3 phase 3 clinical trials evaluating once weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes using basal insulin for the first time (insulin naïve) and in those who have switched from daily basal insulin injections, respectively. In these long-term treat-to-target trials, efsitora showed non-inferior HbA1C reduction compared to the most frequently used daily basal insulins globally.

“Once weekly basal insulins, like efsitora, have the potential to transform diabetes care,” said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. “Many type 2 diabetes patients are reluctant to start insulin because of the burden it places on them. Once-weekly efsitora could potentially make it easier for people with type 2 diabetes to start and manage insulin therapy, while reducing the impact it has on their day-to-day lives.”

QWINT-1 evaluated the efficacy and safety of once weekly efsitora compared to once daily insulin glargine for 52 weeks. The trial randomised adults with type 2 diabetes who are insulin naïve to receive either efsitora once weekly in a single-use autoinjector or insulin glargine once daily. Efsitora was titrated across four fixed doses at four-week intervals, as needed for blood glucose control. All participants treated with efsitora received a starting dose of 100 units followed by a fixed dose escalation to achieve a target fasting blood glucose of 80-130 mg/dL (4.4 – 7.2 mmol/l). Fasting blood glucose was measured every four weeks and participants escalated to fixed dosages of 150 units, 250 units and 400 units as appropriate. Participants with fasting blood glucose greater than 130 mg/dL (7.2 mmol/l) on or after 16 weeks were transferred to flexible dosing. The study’s goal was to provide data supporting real-life applications of fixed dose regimens, which have the potential to make it easier for people living with type 2 diabetes to start and manage insulin therapy.

The trial met its primary endpoint of non-inferior HbA1C reduction with efsitora compared to insulin glargine at week 52. For the efficacy estimand^i,ii, efsitora reduced HbA1C by 1.31% compared to 1.27% for insulin glargine, resulting in an HbA1C of 6.92% and 6.96%, respectivelyⁱⁱⁱ. For the treatment-regimen estimand^iv,v, efsitora reduced HbA1C by 1.19% compared to 1.16% for insulin glargine, resulting in an HbA1C of 7.05% and 7.08%, respectively⁴.

QWINT-3 evaluated the efficacy and safety of once weekly efsitora compared to once daily insulin degludec for 78 weeks in adults with type 2 diabetes currently treated with basal insulin. Participants were randomised 2:1 to receive either efsitora once weekly or insulin degludec once daily.

The QWINT-3 trial met its primary endpoint of non-inferior HbA1C reduction with efsitora compared to insulin degludec at week 26. For the efficacy estimand^vi, efsitora reduced HbA1C by 0.86% compared to 0.75% for insulin degludec resulting in an HbA1C of 6.93% and 7.03%, respectively^vii. For the treatment-regimen estimand^viii, efsitora reduced HbA1C by 0.81% compared to 0.72% for insulin degludec resulting in an HbA1C of 6.99% and 7.08%, respectively^ix.

Additionally, participants taking efsitora or insulin degludec spent approximately two hours more time in range (glucose 70-180 mg/dL (3.9-10.0 mmol/l)) per day for weeks 22-26 compared to baseline. For the efficacy estimand^x, participants taking efsitora spent 62.8% of time in range compared to 61.3% for insulin degludec for weeks 22-26^xi. For the treatment-regimen estimand^xii, participants taking efsitora spent 61.4% of time in range compared to 61% for insulin degludec^xiii. Further, for the efficacy estimand, participants taking efsitora spent 38.3% of time in tight range (glucose 70-140 mg/dL (3.9-7.8 mmol/l)) compared to 36.8% for insulin degludec for weeks 22-26^xiv.

In both QWINT-1 and QWINT-3, the overall safety and tolerability profile of efsitora was similar to that of daily basal insulin therapies for the treatment of type 2 diabetes. In QWINT-1, estimated combined rates of severe or clinically significant (blood glucose <54 mg/dL (<3 mmol/l)) hypoglycaemic events per patient-year of exposure from weeks 0-52 were 0.50 with efsitora vs. 0.88 with insulin glargine. In QWINT-3, estimated combined rates of severe or clinically significant (blood glucose <54 mg/dL (<3 mmol/l)) hypoglycaemic events per patient-year of exposure from weeks 0-78 were 0.84 with efsitora vs. 0.74 with insulin degludec.

Detailed results for QWINT-1 and QWINT-3 will be shared at an upcoming congress and published in a peer-reviewed journal.

About the QWINT clinical trial program

The QWINT phase 3 global clinical development programme for insulin efsitora alfa (efsitora) in diabetes began in 2022 and has enrolled more than 4,000 people living with type 1 or type 2 diabetes across five global registration studies.

QWINT-1 (NCT05662332) was a parallel-design, open-label, treat-to-target, randomised controlled clinical trial comparing the efficacy and safety of efsitora as a once weekly basal insulin using a fixed dose to insulin glargine for 52 weeks in insulin-naïve adults with type 2 diabetes. The trial randomised 796 participants across the U.S., Argentina, Mexico and Puerto Rico to receive efsitora once weekly or insulin glargine once daily administered subcutaneously. All participants treated with efsitora received a starting dose of 100 units followed by a fixed dose escalation to achieve a target fasting blood glucose of 80-130 mg/dL (4.4 – 7.2 mmol/l). Fasting blood glucose was measured every four weeks and participants escalated to fixed dosages of 150 units, 250 units and 400 units as appropriate. Participants with fasting blood glucose greater than 130 mg/dL (7.2 mmol/l) on or after 16 weeks were transferred to flexible dosing. The primary objective of the trial was to demonstrate non-inferiority in reducing HbA1C at week 52 with efsitora compared to insulin glargine.

QWINT-3 (NCT05275400) was a multicentre, randomised, parallel-design, open-label trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec for 78 weeks after a three-week lead-in period, and followed by a five-week safety follow up period, in adults with type 2 diabetes who are currently treated with basal insulin. The trial randomised 986 participants across the U.S., Argentina, Hungary, Japan, Korea, Poland, Puerto Rico, Slovakia, Spain and Taiwan to receive efsitora once weekly or insulin degludec once daily administered subcutaneously. The primary objective of the study was to demonstrate non-inferiority in reducing HbA1C at week 26 with efsitora compared to insulin degludec.

About insulin efsitora alfa

Insulin efsitora alfa (efsitora) is a once-weekly basal insulin, a fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain. It is specifically designed for once-weekly subcutaneous administration, and with its low peak-to-trough ratio, it has the potential to provide more stable glucose levels (less glucose variability) throughout the week. Efsitora is in phase 3 development for adults with type 1 and 2 diabetes.