With once-weekly dosing, insulin efsitora alfa provides similar A1C reduction compared to daily insulin in adults with type 1 diabetes

Detailed results were published in The Lancet and presented simultaneously at the annual meeting of the European Association for the Study of Diabetes (EASD) 2024

INDIANAPOLIS, September 10, 2024 /PRNewswire/ — Eli Lilly and Company (NYSE: LLY ) today announced detailed results from the QWINT-5 Phase 3 study evaluating once-weekly insulin efsitora alfa (efsitora) versus once-daily insulin degludec in adults with type 1 diabetes requiring daily basal and multiple daily mealtime insulin injections. The data was published in The Lancet and presented simultaneously today at the annual meeting of the European Association for the Study of Diabetes (EASD) 2024.

In the study, efsitora met the primary endpoint of non-inferiority A1C reduction at week 26. For efficacy evaluation^1,2efsitora reduced A1C by 0.53% compared to 0.59% for insulin degludec resulting in A1C of 7.37% and 7.32% respectively.³.

In a key secondary endpoint, time within interval⁴ as measured by continuous glucose monitoring (CGM) was similar between efsitor and insulin degludec in the four weeks prior to week 26. Another key secondary endpoint was the estimated composite proportion of patients reporting clinically significant (blood glucose <54 mg/dL) ) or seriously natural⁵ hypoglycemia per patient-year of exposure was similar between efsitor and insulin degludecin during the 52-week study period.

“People with type 1 diabetes need insulin every day. Currently, they can administer their 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, MD., executive director of the International Diabetes Center, HealthPartners Institute. “These new data show that with one weekly dose of basal insulin, efsitora was able to achieve similar A1C reductions to taking an injection of one of the most commonly used basal insulins every day. I look forward to further evaluation of these data, including ways to minimize hypoglycemia, so once-weekly insulin may be one option for personalizing the treatment of type 1 diabetes.”

Overall results

In the study, the estimated pooled rate of clinically significant (blood glucose <54 mg/dL) or severe hypoglycemic events per patient-year of exposure through week 52 was 14.03 with efsitora compared with 11.59 with insulin degludec. There was no evidence of increased duration of hypoglycemia with efsitora compared to insulin degludec based on CGM data.

The estimated rate of severe hypoglycemia per patient-year of exposure through week 52 was 0.14 with efsitora versus 0.04 with insulin degludecin. More than half (64%) of the reported severe hypoglycemia events with efsitor occurred in the first 12 weeks of the study treatment period, and the incidence of severe hypoglycemia in both treatment groups decreased after week 12.

The overall incidence of treatment-emergent adverse events was comparable between treatment groups. Serious adverse events were higher with efsitora compared to insulin degludec, driven by severe hypoglycemia.

“When we launched 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 EmmickMD, Ph.D., Senior Vice President, Product Development, Lilly. “These results highlight the potential of efsitora to help some people living with type 1 diabetes lower their A1C with just one basal insulin injection per week, but also highlight the complexity of treating this chronic disease. With the data we’ve seen from the 3 so far, we are confident in Efsitora’s potential to transform diabetes care and will continue to pursue new treatments until we can eradicate the disease completely.”

Detailed results for QWINT-2 are also presented at EASD and simultaneously published in New England Journal of Medicine.

About the QWINT Clinical Trials Program
The QWINT Phase 3 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 in five global registry studies.

QWINT-5 (NCT05463744) is a multicenter, treat-to-target, randomized, parallel-design, open-label study comparing the efficacy and safety of efsitor as basal insulin once weekly with insulin degludec in treated participants with type 1 diabetes. with daily basal injections and multiple daily mealtime insulin injections. The study consisted of a 52-week treatment period with the primary endpoint measured at 26 weeks. 692 participants across the United States, Argentina, Japan, Poland, Puerto Rico, Slovakia and Taiwan were randomized to once-weekly efsitora or once-daily subcutaneous insulin degludecin. The primary objective of the study is to demonstrate non-inferior reduction in A1C at week 26 with efsitora compared to insulin degludecin. Throughout the study, participants used an unblinded CGM.

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

About Lilly
Lilly is a pharmaceutical company that turns science into medicine 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 worldwide. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently making new discoveries to solve some of the world’s most pressing health challenges: redefining diabetes care; treat obesity and reduce its most devastating long-term effects; strengthen the fight against Alzheimer’s disease; provide solutions to some of the most debilitating immune system diseases; and transform the most difficult cancers into manageable diseases. With each step towards a healthier world, we are motivated by one thing: to make life better for millions more. That includes delivering innovative clinical trials that reflect the world’s diversity and working to ensure that 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

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995), including statements about insulin efsitora alfa as a potential treatment for people with type 1 diabetes and the timeline for future readings, presentations, and other milestones related to insulin efsitor alfa and its clinical trials, and reflect Lilly’s current views and expectations. However, as with all pharmaceutical products, there are significant risks and uncertainties in the process of drug research, development and commercialization. Among other things, there can be no assurance that proposed or ongoing studies will complete as planned, that future study results will be consistent with study results to date, that insulin efsitora alfa will prove to be a safe and effective treatment for type 1 diabetes, that insulin efsitora alfa will be approved regulators or that Lilly will carry out its policies as expected. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly’s expectations, see Lilly’s Form 10-K and Form 10-Q filings with the US Securities and Exchange Commission. Except as required by law, Lilly undertakes no obligation to update forward-looking statements to reflect events after the date of this release.

¹ The efficacy estimate represents the treatment effect if all participants have 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 baseline A1C 7.89% for efsitora and 7.93% for insulin degludecin.
⁴ Glucose 70-180 mg/dL.
⁵ Every event that happened between midnight and 6 am
⁶ The treatment plan represents the efficacy regardless of adherence to the study drug or the introduction of rescue therapy for persistent severe hyperglycemia.
⁷ From baseline A1C 7.88% for efsitora and 7.94% for insulin degludecin.
⁸ 95% CI for treatment difference (-0.077% to 0.181%).
⁹ Blood sugar <54 mg/dL.

SOURCE Eli Lilly and Associates