Daniel M. Skovronsky
Executive Vice President; Chief Scientific Officer and President, Lilly Research Laboratories; Presi at Eli Lilly and Company
Thanks, Lucas. Lilly R&D had another productive quarter. I'll cover pipeline progress in Q4, then the 2024 key events and finally provide potential key events for 2025. Since our last earnings call, two new indications were approved in the US, ZEP bound for obstructive sleep apnea and adults with obesity and for moderate-to-severe Crohn's disease. Both approvals are important milestones and mark an expansion in the number of patients who can benefit from each of these medicines.
First, moving to regulatory submissions, we completed submissions in the US and EU for tirzepatide for heart failure and global submissions for mlinestrant for metastatic breast cancer and for JPERCA with the Brewin CLL-321 data. I'm also pleased to share that we've submitted an update to the US label to include the dosing modification data from and the FDA has granted the submission a priority review. In our Phase-3 portfolio, we initiated a new program for in obstructive sleep apnea.
This program includes two studies under the same master protocol to evaluate if people with obstructive sleep apnea and obesity can benefit from orphroglipron. After was approved in the US as the first and only prescription medicine for obstructive sleep apnea, we're excited to explore if an oral GLP-1 can also deliver a benefit in this disease. Earlier in the pipeline, we advanced the second oral GLP-1 into Phase-2 in obesity and advanced Altrecabart into Phase-2 for ulcerative colitis.
Three Phase-2 assets and one Phase-1 asset have been discontinued based on clinical readouts. In Q4, we also began Phase-1 studies for four new molecules, one in each of our therapeutic areas. Q4 capped off a productive year of advancing new medicines at Lilly. In total, over the year, we started eight new Phase-3 programs. We disclosed Phase-3 data from 21 trials, including 17 major publications in top-tier medical journals. We received regulatory approvals for two new medicines at and as well as many new indications around the world.
And we added 14 new programs to the early phase pipeline. On Slide 16, we detail these outcomes for our 2024 milestones. I'm pleased that nearly all of our anticipated milestones came to fruition positively in 2024. Turning our focus to 2025, slide 17 shows key R&D milestones we expect this year. Starting with our late-stage portfolio, we expect to initiate two new Phase-3 programs this year. First, in oncology, we'll begin an adjuvant non-small cell lung cancer Phase-3 program for our KRASG12C inhibitor, olomerasib, building on its ability to be administered with immunotherapy.
Our current metastatic program is progressing well and we've aligned with the FDA on our Phase-3 dose through the Project Optimus pathway. We shared a clinical update at the World Conference on lung cancer last fall, and we are encouraged by the ability to safely combine with other agents. Our new Phase-3 program will focus on moving to an earlier setting and combining with existing approved agents in both resectable and unresectable KRASG12C mutant lung cancer to prevent cancer from recurring.
The second program is in cardiometabolic health, where we plan to initiate a Phase-3 trial for orphroglipron in hypertension, adding to the ongoing trials in type-2 diabetes, obesity and obstructive sleep apnea. I'm excited that this year we're looking-forward to reading out multiple trials. We expect to see data from up to five studies in type-2 diabetes and two studies in obesity.
Our goal is to generate efficacy, safety and tolerability profile that is similar to that of an injectable single-acting GLP-1, but through an orally available medicine. The first Phase-3 trial to read-out will be ACHIVE-1, which is a 40-week study in-patients with type-2 diabetes. These patients have a baseline hemoglobin A1c between 7% and 9.5% and a body mass index of 23 or greater. The trial utilizes six escalating doses in four-week increments to a maximum dose of 36 milligrams.
Based on prior studies of as well as other GLP-1 therapies, we expect weight-loss in people with diabetes to be significantly less than in people living with obesity who do not have diabetes. We anticipate will read-out in Q2 this year, followed by up to four additional type-2 diabetes trials in the second-half of 2025 and a potential submission for this indication in 2026. The Phase-3 trials in people with obesity attain one and attain two are expected to read-out in Q3 of this year. These trials will form the basis of our first regulatory submissions, which will be for the treatment of obesity and we expect to occur late in 2025.
This year, we also expect data from the tirzepatide cardiovascular outcome study surpass CBOT. Of course, this is an event-based trial and the timeline is dependent on the accrual of cardiovascular events. We anticipate data in Q3. While designed to measure both non-inferiority and superiority compared to Trulicity, the positive outcome in either would demonstrate that tirzepatide reduces the risk of cardiovascular outcomes and would support a labeled indication.
Late this year, we expect to see the first data from a triple-acting incretin, retitrutide, which combines GLP-1, GIP and glucagon. We believe this potential new medicine can deliver even more weight-loss than tirzepatide and could potentially provide additional health benefits. The initial study to read-out is a 68-week study in-patients with osteoarthritis of the knee who have a body mass index of 27 or greater. We'll also see multiple additional JPERCA datasets this year.
Physician feedback is very positive on experience with JPERCA in the currently approved indications and we hope that generating data in earlier lines of therapy will enable broader use within CLL and MCL. We could see data from additional trials in the first-line of BTK naive settings this year. Moving to neurodegeneration, while we don't have a key event listed in 2025 for donanemab, we're closely watching the preclinical Alzheimer's disease study Trailblazer ALS-3.
This trial screen patients with a blood-based diagnostic and utilized a fixed duration of treatment with donanemab. By moving earlier in disease progression, the goal is to reduce the risks of developing any symptoms of Alzheimer's disease. While the current primary completion is projected for 2027, the study will read-out when the target number of progression events are accrued. A new focus area for us in 2025 will be to study potential new applications of biology across diseases in neuroscience and immunology.
With a pipeline of in clinical development and deep scientific expertise in this space, is well-positioned to match the biologic properties of specific molecules to the desired indications being studied. We plan to start several clinical trials, assessing potential benefits of our incretins in areas that could include brain health, substance use disorder, pain, neuropsychiatry and inflammation. We'll be prepared to move rapidly into Phase-3 trials based on clinical data and where our conviction is high.
Lastly, we expect a number of important regulatory submissions in 2025, including for obesity as I detailed, insulin alpha for type-2 diabetes, tirzepatide for cardiovascular outcomes and multiple potential datasets for JPERCA. 2025 will be another exciting year for Lilly R&D.
Now I'll turn the call-back to Dave for some closing remarks.
