Daniel M. Skovronsky
Executive Vice President; Chief Scientific Officer & President, Lilly Research Laboratories; Preside at Eli Lilly and Company
Thanks, Gordon.
It's been another busy quarter. I'll start with comments on the Kisunla FDA approval, then the tirzepatide heart failure Phase III readout. Then finally, I'll cover the rest of the updates for the quarter. We are, of course, very excited about the FDA approval of Kisunla for treatment of Alzheimer's disease. This followed the June Advisory Committee meeting where we had another chance to present and discuss the compelling data package characterizing the safety and efficacy of this medicine. We were pleased by the discussion of the FDA advisers, particularly with regard to our data supporting stopping of Kisunla therapy when amyloid plaques are removed to minimal levels. In our trial, nearly half of study participants completed their course of treatment with Kisunla in 12 months. We believe limited duration therapy, along with a once monthly infusion schedule, could result in lower patient out-of-pocket treatment costs and fewer infusions required.
The vote was unanimously positive on all questions presented. Then a few weeks later, the FDA approved Kisunla, including labeling that physicians may consider stopping dosing of Kisunla based on reduction of amyloid plaques. Following the July approval, we launched Kisunla, and we're delighted to see that patients have already begun receiving this new Lilly medicine as part of clinical practice. We note that Kisunla is broadly covered for Medicare patients through approved CED registries. Regulatory reviews continue around the world with potential action yet this year in several countries. We're pleased to have recently received a positive opinion for donanemab from the Pharmaceuticals and Medical Devices Agency in Japan. And finally, our Phase III prevention study, TRAILBLAZER ALZ 3, continues to progress as planned.
Moving to tirzepatide. On Slide 14, you'll see the recent positive results of our SUMMIT Phase III trial, which evaluated tirzepatide for the treatment of heart failure with preserved ejection fraction and obesity. This study demonstrated statistically significant improvements in both primary endpoints for tirzepatide maximum tolerated dose compared to placebo. In the first primary endpoint, tirzepatide reduced the risk of worsening heart failure by 38% compared to placebo as measured by a composite outcome of heart failure urgent visit or hospitalization, oral diuretic intensification or cardiovascular death. The median follow-up for this endpoint was 104 weeks.
In the second primary endpoint, tirzepatide significantly improved heart failure symptoms and physical limitations compared to placebo as measured by the Kansas City Cardiomyopathy Questionnaire, KCCQ Clinical Summary score. Main changes from baseline in this measurement is 24.8 points for tirzepatide, while placebo was 15 points based on the efficacy estimate at 52 weeks. All key secondary endpoints were met in the study, including mean body weight reduction of 15.7% compared to 2.2% for placebo. The overall safety profile of tirzepatide in the SUMMIT trial was consistent with previously reported tirzepatide studies, including SURMOUNT and SURPASS. We will present detailed results at an upcoming medical meeting and submit to a peer review journal. We plan to submit results to the FDA and other regulatory agencies starting later this year.
In other updates across our portfolio, Slide 15 shows select pipeline opportunities as of August 6.
Slide 16 shows potential key events for the year. I'll start with updates in cardiometabolic health, which is the new name of our internal business, formerly known as Lilly diabetes and obesity. In June, we published detailed results for our Phase III trials of tirzepatide for the treatment of moderate to severe obstructive sleep apnea and obesity in the New England Journal of Medicine, and we presented results at the American Diabetes Association Meeting. All primary and key secondary endpoints were achieved in these studies.
Notably, in one of our key secondary endpoints, as shown on Slide 17, tirzepatide demonstrated that up to 51.5% of participants met the criteria for disease resolution of sleep apnea. We've now submitted tirzepatide for the treatment of moderate to severe obstructive sleep apnea and obesity to the FDA as well as the EMA. We are pleased that the FDA has granted breakthrough therapy designation, and we expect US regulatory action as early as the end of 2024, which will be dependent on the FDA granting priority review. Also in June, we published results in the New England Journal from our Phase II trial of tirzepatide for metabolic dysfunction associated steatohepatitis, or MASH, with Stage II or III fibrosis and we presented these results at the European Association for the Study of the Liver.
We are pleased to show that in a secondary endpoint, more than half of the patients taking tirzepatide achieved improvement in fibrosis at 52 weeks as shown on Slide 18. We're engaged with regulatory authorities on a potential Phase III registration strategy, and we're also encouraged by the potential read-through of these results to retatrutide, which also showed significant improvements in liver fats in Phase II. This quarter, we also announced top line data from two Phase III trials for our once weekly insulin called efsitora alfa, the QWINT-2 and QWINT-4 trials for the treatment of type 2 diabetes each met their primary endpoints of non-inferior A1c reduction.
QWINT-2 compared efsitora to once-daily insulin degludec for 52 weeks in insulin naive adults. QWINT-4 compared efsitora to insulin glargine for 26 weeks in adults previously treated with daily basal insulin and at least two injections per day of mealtime insulin. In both QWINT-2 and QWINT-4, efsitora was safe and well tolerated. Detailed trial results will be presented in September at the European Association for the Study of Diabetes Annual Meeting. We look forward to sharing additional data from the QWINT program later this year. We are pleased with our progress to provide breakthrough innovation to patients who require insulin, progressing our glucose sensing insulin receptor agonist molecule in Phase I and investing in approaches aimed at disease modification for type 1 diabetes, such as islet cell therapy.
In other late-phase updates, we've initiated TRIUMPH outcomes, a Phase III trial evaluating cardiovascular outcomes and renal function for patients taking retatrutide. Earlier in our cardiometabolic pipeline, you'll see additional incretin molecules in Phase I. Incretins are an important part of our portfolio strategy and having multiple molecules in clinical development offers us potential optionalities as we look at opportunities to help patients across mechanisms, indications, dosages, formulations and treatment schedules.
To highlight a few, GLP-1 NPA2 is a small molecule non-peptide agonist of the GLP-1 receptor designed for once daily oral administration. We expect this asset to move to Phase II later this year, so we now identify it on our pipeline slide whereas it had previously been listed as not disclosed. Given the diversity of indications to potentially pursue with incretins, we are excited about the possibility of having another oral option to help more patients with different diseases. We also highlight today GIP/GLP-1 coagonist 3, which is a next-generation dual agonist molecule and we are planning to explore weekly and monthly dosing given its longer halflife. Elsewhere in our cardiometabolic health portfolio, we have stopped development of our NRG4 agonist as the profile was insufficient for further clinical development.
Turning to oncology. We are pleased that Jaypirca has now been approved in Japan for people with relapsed or refractory mantle cell lymphoma who are resistant or intolerant to other BTK inhibitors. In early phase oncology, we've initiated the Phase I trial for a second Nectin-4 ADC. We view this as an important target and having two compounds in the clinic provides more opportunities to improve outcomes for patients. We've also initiated a Phase I trial for our ADC targeting the folate receptor. This asset, which came from our acquisition of Mablink is the next-generation construct designed to have efficacy at all folate receptor expression levels and with an improved therapeutic index relative to existing agents.
We're also announcing that we've terminated the LOXO-783 program, which targeted PI3 kinase alpha. We evaluated the ongoing clinical data from the program and compared the molecule to next-generation candidates that we have progressed from our discovery efforts. We believe our next molecules have greater potential to benefit patients. We look forward to putting our next candidate into the clinic in 2025 and sharing more about its profile later this year. In immunology, we've now submitted mirikizumab for the treatment of moderately to severely active Crohn's disease in Japan. We've terminated development for our GITR antagonist due to insufficient efficacy. We also announced our acquisition of Morphic. And pending completion of the deal, we plan to reflect the oral alpha-4-beta-7 integrin inhibitor, MORF-057, in Phase II for ulcerative colitis and Crohn's disease.
Finally in neuroscience, our anti-tau small molecule OGA inhibitor, recently concluded its Phase II study in early symptomatic Alzheimer's disease. OGA failed to meet the primary endpoint of decreasing the change from baseline as measured by iADRS in either of the two dose levels tested. We're reviewing the data for presentation of detailed results of the study at the clinical trials in Alzheimer's Disease conference later this year. While this negative outcome is disappointing, we remain committed to tau as a high conviction target in Alzheimer's disease and plan to continue studying tau biology.
I'll now turn the call back to Dave for closing remarks.
