Detailed results were published in The Lancet and simultaneously presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2024
INDIANAPOLIS, IN, USA I September 10, 2024 I Eli Lilly and Company (NYSE: LLY) today announced detailed results from the QWINT-5 phase 3 trial evaluating once-weekly insulin efsitora alfa (efsitora) compared to once-daily insulin degludec in adults with type 1 diabetes who require daily basal and multiple daily mealtime insulin injections. The data were published in The Lancet and simultaneously presented today at the European Association for the Study of Diabetes (EASD) Annual Meeting 2024.
In the trial, efsitora met the primary endpoint of non-inferior A1C reduction at week 26. For the efficacy estimand1,2, efsitora reduced A1C by 0.53% compared to 0.59% for insulin degludec resulting in an A1C of 7.37% and 7.32% respectively3.
In a key secondary endpoint, time in range4 as measured by continuous glucose monitoring (CGM) was similar between efsitora and insulin degludec during the four weeks prior to week 26. In an additional key secondary endpoint, the estimated combined rates of patient-reported clinically significant (blood glucose <54 mg/dL) or severe nocturnal5 hypoglycemic events per patient-year of exposure were similar between efsitora and insulin degludec over the 52-week study period.
“People with type 1 diabetes need insulin every day. Currently, they can deliver the insulin using an automated insulin delivery system or by taking a daily basal insulin injection and multiple mealtime insulin injections each day,” said Richard Bergenstal, M.D., executive director of the International Diabetes Center, HealthPartners Institute. “This new data shows that with one dose a week of basal insulin, efsitora was able to achieve a similar A1C reduction as taking an injection of one of the most used background insulins every day. I look forward to further evaluation of these data, including ways to minimize hypoglycemia, so once-weekly insulin can be one option for personalizing the management of type 1 diabetes.”
Full Results
| QWINT-5 Study: Primary and Secondary Endpoints | ||
| Efficacy Estimand | Treatment-Regimen Estimand6 | |
| Primary Endpoint – A1C Reduction (Resulting A1C) at 26 Weeks | ||
| Efsitora | -0.53% (7.37%) | -0.51% (7.41%)7 |
| Insulin degludec | -0.59% (7.32%) | -0.56% (7.36%)8 |
| Secondary Endpoint – Percent Time in Range During the 4 Weeks Prior to Week 26 | ||
| Efsitora | 52.8 % | 52.5 % |
| Insulin degludec | 53.1 % | 52.9 % |
| Secondary Endpoint – Estimated Rate of Clinically Significant9 or Severe Nocturnal Hypoglycemic Events Per Patient-Year of Exposure through 52 Weeks | ||
| Efsitora | 1.99 | |
| Insulin degludec | 1.96 | |
In the trial, estimated combined rates of patient-reported clinically significant (blood glucose <54 mg/dL) or severe hypoglycemic events per patient-year of exposure through week 52 were 14.03 with efsitora vs. 11.59 with insulin degludec. There was no evidence of increased duration of hypoglycemia with efsitora compared to insulin degludec based on CGM data.
Estimated rates of severe hypoglycemic events per patient-year of exposure through week 52 were 0.14 with efsitora vs. 0.04 with insulin degludec. More than half (64%) of the reported severe hypoglycemic events with efsitora took place during the initial 12 weeks of the trial’s treatment period and incidence of severe hypoglycemia in both treatment groups declined after week 12.
Overall incidence of treatment-emergent adverse events were comparable across treatment groups. Serious adverse events were higher in efsitora compared to insulin degludec, driven by severe hypoglycemic events.
“When we commercialized insulin more than 100 years ago, it marked the beginning of our commitment to people living with type 1 diabetes – today’s announcement continues that legacy,” said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. “These results underscore the potential of efsitora to help some people living with type 1 diabetes lower their A1C with only one basal insulin injection per week, while also highlighting the complexity of treating this chronic disease. With the data we have seen from our phase 3 program so far, we are confident in efsitora’s potential to transform diabetes care and will continue to pursue new treatment options until we can eliminate the disease entirely.”
Detailed results for QWINT-2 are also being presented at EASD and simultaneously published in The New England Journal of Medicine.
About the QWINT clinical trial program
The QWINT phase 3 global clinical development program 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-5 (NCT05463744) is a multicenter, treat-to-target, randomized, parallel-design, open-label study comparing the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec in participants with type 1 diabetes treated with daily basal and multiple daily mealtime insulin injections. The trial consisted of a 52-week treatment period with the primary endpoint measured at 26 weeks. 692 participants across the U.S., Argentina, Japan, Poland, Puerto Rico, Slovakia and Taiwan were randomized to receive efsitora once weekly or insulin degludec once daily administered subcutaneously. The primary objective of the study is to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin degludec. Throughout the study, participants used unblinded CGM.
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, 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.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY
1 The efficacy estimand represents the treatment effect had all participants adhered to the study drug without initiating rescue therapy for persistent severe hyperglycemia.
2 95% CI for treatment difference (-0.075% to 0.19%).
3 From a baseline A1C of 7.89% for efsitora and 7.93% for insulin degludec.
4 Glucose 70-180 mg/dL.
5 Any event that occurred between midnight and 6 a.m.
6 Treatment-regimen estimand represents the efficacy irrespective of adherence to the investigational medicine or introduction of rescue therapy for persistent severe hyperglycemia.
7 From a baseline A1C of 7.88% for efsitora and 7.94% for insulin degludec.
8 95% CI for treatment difference (-0.077% to 0.181%).
9 Blood glucose <54 mg/dL.
SOURCE: Eli Lilly
