Daniel M. Skovronsky
Executive Vice President; Chief Scientific Officer and President, Lilly Immunology at Eli Lilly and Company
Thanks, Anat.
Let me start with our exciting announcement from earlier this month. That was the positive Phase 3 results from the SURMOUNT-OSA studies, which evaluated tirzepatide for treatment of adults with obesity and moderate to severe obstructive sleep apnea, known as OSA. OSA is a sleep-related breathing disorder characterized by complete or partial collapse of the upper airway during sleep. OSA can have serious cardiometabolic complications, contributing to hypertension, coronary heart disease, stroke, heart failure, atrial fibrillation and even Type 2 diabetes. The need is significant. OSA impacts 80 million people in the U.S., with more than 20 million people suffering from moderate to severe OSA. We also know that a substantial majority, approximately 70%, of people with OSA also live with obesity.
While there are pharmaceutical treatments for the excessive day-time sleepiness associated with OSA, tirzepatide could potentially be the first pharmacological treatment for the underlying disease.
As shown on Slide 12, SURMOUNT-OSA was comprised of two separate trials run under one master protocol. Study 1 evaluated tirzepatide in participants not currently on positive airway pressure, or PAP, therapy. While Study 2 evaluated tirzepatide in patients who had used PAP for at least three months prior to the study and planned to continue PAP therapy during the entire course of the trial. The total of 469 participants were enrolled across these studies. Each study randomized participants to either maximum tolerated dose approved for tirzepatide, which could be 10 milligrams or 15 milligrams or to placebo, and patients were followed on therapy for 52 weeks.
On Slide 13, we show the results of Study 1. For the efficacy estimate, on mean Apnea Hypopnea Index, or AHI, tirzepatide led to a mean reduction of 27.4 events per hour compared to a mean AHI reduction of 4.8 events per hour for placebo. This difference was highly statistically significant. AHI baseline values were 52.9% and AHI was reduced by 55% in the tirzepatide arm. We also saw a mean body weight reduction of 18.1% with tirzepatide treatment, consistent with our expectations for the study. This was, of course, also statistically significant versus placebo.
On Slide 14, we show the results of Study 2. In this population, for the efficacy estimate, tirzepatide led to a mean AHI reduction of 30.4 events per hour compared to a mean AHI reduction of 6.0 events per hour for placebo. The baseline AHI was 46.1% in the tirzepatide arm, and mean AHI reduction was 62.8%. Again, we saw impressive weight loss with a mean body rate reduction of 20.1% from baseline. These results were also all highly statistically significant.
In both studies, the overall safety profile was similar to previously reported SURMOUNT and SURPASS trials. The most commonly reported adverse events were gastrointestinal related and generally mild to moderate in severity, with the most commonly reported gastrointestinal adverse events for patients treated with tirzepatide being diarrhea, nausea, vomiting and constipation.
Prior to the study read-out, we noted investor questions about what level of weight loss we would see, given several factors that were uniquely combined in this study of tirzepatide. First, the primary aim of the study was not treatment of obesity. Second, that the population was approximately 70% males, in whom, weight loss can be harder to achieve with incretin medicines. Third, there was a particularly high baseline BMI in this population. And finally, the use of the 10-milligram or 15-milligram maximum tolerated dose approach. We were, therefore, highly reassured to see weight loss observed across the two studies at 52 weeks was nearly 20% despite this difficult-to-treat population. Consistent with other Phase 3 studies of tirzepatide at the 52-week time point, we did not see weight loss plateau. We'll present detailed results of SURMOUNT-OSA during a symposium at ADA on June 21st. Additionally, we plan to submit to the FDA and other global regulatory agencies beginning mid-year.
Moving to the other updates across our portfolio. Slide 15 shows select pipeline opportunities as of April 26, and slide 16 shows potential key events for the year. We're pleased to share that results were positive in QWINT-4, the first Phase 3 study of insulin efsitora alfa, our once-weekly basal insulin. This study evaluated efsitora compared to insulin glargine in adult participants with Type 2 diabetes who are on multiple daily insulin injections. In the coming weeks, we expect to report top-line results from QWINT-4 as well as QWINT-2, which is evaluating efsitora compared to degludec in adults with Type 2 diabetes who are naive to basal insulin. Together, these are the first two of five studies in the efsitora Phase 3 program.
Additional updates in our late-stage diabetes and obesity pipeline include results of the EMPACT-MI study, showing Jardiance had a 10% relative risk reduction in the primary composite endpoint of time-to-first hospitalization due to heart failure or all-cause mortality versus placebo, which did not reach statistical significance. We've completed enrollment for SURMOUNT-MMO with over 15,000 participants and for both orforglipron studies in chronic weight management, ATTAIN-1 and ATTAIN-2, which together enrolled 4,500 participants. Finally, we've now initiated the TRANSCEND Phase 3 program, studying retatrutide in Type 2 diabetes.
In the cardiovascular disease area, we're excited to have initiated the Phase 3 trial for lepodisiran, the subcutaneous injectable SiRNA. This study will evaluate the efficacy and improving cardiovascular outcomes for participants with high lipoprotein(a) who have cardiovascular disease, or at a risk of heart attack or stroke. We are evaluating the efficacy of lepodisiran in both secondary and high-risk primary prevention. And we hope this will one day offer healthcare providers a treatment option for a broad group of patients at increased cardiovascular risk due to high LPA levels. Earlier in our diabetes and obesity pipeline, we've now initiated a Phase 2 monotherapy study, evaluating eloralintide, our selective amylin receptor agonist in obesity.
Turning to oncology, we made the decision to terminate for futility the Phase 3 CYCLONE-3 trial, evaluating Verzenio in metastatic hormone-sensitive prostate cancer following an interim analysis. This concludes development of Verzenio in prostate cancer following last quarter's announcement that the CYCLONE-2 study did not meet its primary endpoint. In early oncology development, we've initiated Phase 1 trials for two new assets. The first is our Nectin-4 ADC, which came from our acquisition of Emergence Therapeutics. The second is PNT2001, which came from our acquisition of Point Biopharma. We're encouraged by what we're seeing in our oncology portfolio and expect 2024 to be particularly productive.
Along with the Nectin-4 ADC and PNT2001 start, we expect at least three other new molecules to enter the clinic this year. We look forward to sharing more details with the investment community at an oncology-focused investor event hosted by the Lilly Oncology team. This event will take place on the evening of Sunday, June 2 in Chicago, in conjunction with the ASCO Annual Meeting, and will also be available via webcast. We plan to provide an update on our oncology strategy and pipeline opportunities. Additional details will be available soon regarding this event.
Turning to neuroscience. Last month, we announced that the FDA plans to convene a meeting of the Peripheral and CNS Drugs Advisory Committee to discuss donanemab in early symptomatic Alzheimer's disease. We expect the Advisory Committee meeting will take place in mid-2024, but the exact date will be confirmed when it appears in the federal register. We expect the focus to be around the safety and efficacy profile of donanemab, along with unique aspects of the clinical program. We remain confident in donanemab's potential to offer very meaningful benefits to patients and look forward to addressing the FDA's questions in this form. Additionally, we made the decision to discontinue investigation of GBA1, our gene therapy asset in Gaucher disease Type 2. Phase 2 studies in Parkinson's disease and Gaucher disease Type 1 are still underway and have not been impacted by this decision.
Finally, in immunology, we submitted mirikizumab to the FDA and EMA for approval for use in adults with moderately to severely active Crohn's disease. In the U.S., we've resubmitted lebrikizumab's application to the FDA for moderate to severe atopic dermatitis. This is following a Complete Response Letter based on inspection findings at a third-party manufacturer. As a reminder, the letter stated no concerns with the clinical data package, safety or label. We expect regulatory action in the second-half of this year.
We're also announcing that in the coming months, we'll be initiating Phase 3 studies evaluating lebrikizumab in two new indications, chronic rhinitis with nasal polyposis and allergic rhinitis due to perennial allergens. Lebrikizumab will be the first biologic to be evaluated in Phase 3 for allergic rhinitis. We're optimistic about the potential of lebrikizumab to be an important treatment option in these patient populations as well as in atopic dermatitis. In earlier-stage immunology development, we advanced our CD19 antibody into Phase 2 for multiple sclerosis.
I'll now turn the call back to Dave for closing remarks.
