Insulin Glargine(Boehringer Ingelheim)

Eli Lilly says it plans to take its efsitora data package to global regulatory agencies by the end of this year. With detailed readouts from a suite of late-stage trials now on tap, Eli Lilly is heading to regulators in pursuit of a green light for its once-a-week insulin asset efsitora alfa.Lilly on Sunday provided a comprehensive look at positive results from its QWINT-1, QWINT-3 and QWINT-4 studies, which assessed efsitora in Type 2 diabetes patients using insulin for the first time, those who previously used daily basal insulin and those who previously used daily basal insulin and mealtime insulin, respectively.Efsitora—which would allow diabetes patients to cut back on more than 300 insulin injections per year if approved—helped patients achieve noninferior A1C (blood sugar) reduction versus daily basal insulin in all three studies, helping the clutch of trials meet their primary endpoints, Lilly said.With those winning results in hand, Lilly says it plans to take its efsitora data package to global regulatory agencies by the end of this year. Overall, Lilly has unveiled positive readouts from five different trials in the QWINT program, which kicked off in 2022.The momentum behind efsitora comes as Lilly’s chief metabolic medicine rival Novo Nordisk has struggled to win clearance for its own once-weekly insulin in the U.S. That said, Novo’s drug, known commercially as Awiqli, already boasts approvals in territories like Europe, Canada, Japan and Australia. Breaking down the results, efsitora helped reduce patients’ A1C by 1.31% versus 1.27% for insulin glargine at the QWINT-1 study’s 52-week mark. In QWINT-3, efsitora reduced A1C by 0.86% at Week 26 and in QWINT-4 by 1.07% over the same time frame, compared to 0.75% for insulin degludec and 1.07% for insulin glargine, respectively.Lilly also unveiled results from several key secondary endpoints in QWINT-3 and 4. In the former trial, efsitora patients’ glucose levels were in range 62.8% of the time during the four weeks leading up to Week 26 of the study, compared to 61.3% of the time for those on insulin degludec.In QWINT-4, meanwhile, efsitora helped 39.5% of patients achieve an A1C less than 7% at Week 26 without nocturnal hypoglycemia, compared to 36.6% of patients receiving insulin glargine.For QWINT-1, Lilly says it titrated efsitora to four fixed doses at four-week intervals, as needed for blood glucose control. In QWINT-3 and 4, efsitora was given via traditional insulin dosing with adjustments according to each patient’s glucose level, the company explained.Efsitora’s safety in the three studies was on par with insulin glargine and insulin degludec, which are among the most commonly used daily basal insulins, Lilly noted in its release.In the QWINT-1 study, patients on efsitora experienced roughly 40% fewer hypoglycemic events—when a person’s blood sugar drops too low—compared to insulin glargine, Lilly pointed out.Meanwhile, at the QWINT-1 study’s 52-week mark, the estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure was 0.50 with efsitora versus 0.88 with insulin glargine. For QWINT-3, those results clocked in at 0.84 with efsitora versus 0.74 with insulin degludec at 78 weeks, while the QWINT-4 results came in at 6.6 with efsitora versus 5.9 with insulin glargine at 26 weeks."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," Jeff Emmick, M.D., Ph.D., Lilly’s senior vice president of product development, said in a statement.  "These results reinforce the potential for once-weekly efsitora to help reduce the overall burden of insulin therapy through a simplified treatment approach”Across the QWINT program, Lilly has looked at efsitora’s performance in more than 3,000 Type 2 diabetes patients. QWINT-1 enrolled 795 participants versus 986 for QWINT-3 and 730 for QWINT-4.Lilly presented the latest trio of readouts over the weekend at the 85th American Diabetes Association Scientific Sessions in Chicago. The results from QWINT-1 were also published in The New England Journal of Medicine, while data from QWINT-3 and 4 have made their way into The Lancet, according to Lilly.The detailed look at QWINT-1, 3 and 4 follows a succession of positive readouts from the program since last May, when Lilly first revealed that the QWINT-2 and 4 studies had met their A1C noninferiority endpoints. QWINT-2 was specifically designed to assess whether the use of GLP-1 medicines for diabetes like Mounjaro or Novo’s Ozempic could weigh on efsitora’s efficacy.Lilly is betting big on efsitora’s potential to both improve treatment for patients already using daily insulin and encourage new patients to start using the medication.“Imagine 313 fewer injections per year,” Paul Owens, VP of global brand development for insulins and glucagon at Lilly, said of the drug’s promise in an interview with Fierce Biotech last year. “We believe it has the potential to really improve adherence … and for some, the innovation of a simple, once-weekly approach to dosing could really mean the difference between starting the treatment and not.”Diabetes patients have been grappling with daily insulin dosing for nearly a century, and those repetitive injections in response to blood glucose tests can become a “huge burden” for people living with the disease, Owens said at the time.Though Novo Nordisk beat Lilly to the punch launching its weekly insulin product Awiqli overseas, Lilly now appears poised to take the lead in the U.S. Last July, the FDA rejected Novo’s application for the product, which is also known as insulin icodec. Novo credited the rejection to “requests related to the manufacturing process and the type 1 diabetes indication.” At the time, Novo cautioned that it didn’t expect to resolve the issue by the end of 2024.The snub followed an unfavorable vote from an FDA advisory committee, which largely revolved around questions about icodec’s potential to cause low blood sugar.Ultimately, seven of 11 panelists agreed that the data Novo presented were not sufficient to conclude that the benefits of icodec outweighed the risks for adults with Type 1 diabetes.

Patients that use rapid-acting insulin to help control their blood sugar spikes have a biosimilar option in Sanofi's Merilog, which has gained FDA approval. More than three years after approving two biosimilars referencing Sanofi’s long-acting insulin Lantus, the FDA has signed off on a rapid-acting insulin biosimilar for the first time.The agency has given a thumbs up to Sanofi’s Merilog (insulin-aspart-szjj) as the first biosimilar to Novo Nordisk’s NovoLog for patients with diabetes. Insulin aspart is delivered by a subcutaneous shot 5 to 10 minutes before mealtime to help patients control glucose and limit blood sugar spikes.Merilog will be provided by prefilled pen in a 3 mL dose or in a multiple-dose 10 mL vial. It is for adults and pediatric patients age 6 and older.The approval is backed by a phase 3 trial of 597 patients with type 1 and type 2 diabetes who received multiple shots daily. At week 26, blood sugar levels were similar for those who received the biosimilar and those on the reference product, confirming Merilog’s non-inferiority.Of the roughly 38 million in the U.S. with diabetes, 8.4 million use either a rapid-acting or long-acting insulin, or both, the FDA said. The high cost of insulin has led some patients to ration their use, triggering high-profile calls from U.S. lawmakers for companies to drop their prices.In 2023, Eli Lilly revealed a plan to cut the cost of most of its insulins by 70%. Less than two weeks later, Novo Nordisk announced a planned 75% reduction in the cost of NovoLog.Then a few days later, Sanofi followed suit with a 78% slashing of the price of Lantus. The company also said it would cap the monthly out-of-pocket cost for Lantus at $35 for those with commercial insurance.  NovoLog and Novo Nordisk’s other rapid-acting insulin follow-on Fiasp are among the drugs subject to government price negotiations under the Inflation Reduction Act. The new prices will be enacted at the start of next year.In July 2021, the FDA approved Biocon and Viatris’ Semglee (insulin glargine-yfgn) as the first biosimilar to Lantus. Five months later, the U.S. regulator endorsed Eli Lilly’s version of the drug, called Rezvoglar (insulin glargine-aglr).