Daniel M. Skovronsky
Senior Vice President and Chief Scientific and Medical Officer at Eli Lilly and Company
Thank you Anat. 2021 was a remarkable year for Lilly's pipeline. We delivered positive data on five molecules tirzepatide, donanemab, pirtobrutinib, mirikizumab and lebrikizumab, all of which have the potential to launch in the next two years. And we're excited about the potential these molecules hold for patients. In addition, we launched and submitted several key new indications for in-market products including important new indications for Verzenio and Jardiance. And also we advanced our early stage pipeline.
Just a few weeks ago we provided an extensive R&D update across our therapeutic areas and shared our excitement about the next wave of innovation coming from Lilly. As a result, today's R&D update will be brief and focus on the progress we've made since our last earnings call. Slide 14 shows select pipeline opportunities as of January 31 and slides 15 and 16 show a recap of 2021 key events and potential key events for 2022. In Diabetes, with the recent submission in Japan, we've now submitted tirzepatide across all major geographies for the treatment of Type 2 diabetes. We look forward to potential approvals for this important medicine this year.
We anticipate U.S. regulatory action in Type 2 diabetes as well as the top line readout from SURMOUNT-1 both by mid-year. In Japan, we submitted Jardiance for heart failure with preserved ejection fraction, and received approval for Jardiance for treatment of heart failure with reduced ejection fraction. Moving to Oncology, we shared encouraging updated data at ASH for pirtobrutinib for both chronic lymphocytic leukemia and mantle cell lymphoma. We continue to progress this molecule and initiated another Phase 3 study in first-line CLL comparing pirtobrutinib to chemo immunotherapy.
During our December meeting, we also announced the initiation of a rolling submission for pirtobrutinib per MCL in the U.S. We plan to complete this submission this year with anticipated regulatory action in early 2023 and we're excited to potentially bring this important medicine to patients on this accelerated timeline. For Verzenio, we received approval for high-risk early breast cancer in Japan for the Cohort 1 population studied in monarchE and are pleased that this approval represents 90% of the intent to treat population.
We've also made the difficult decision to terminate further enrollment in the Phase 3 study of Verzenio for HR positive, HER-2 positive early breast cancer in response to the changing treatment landscape and global enrollment challenges. Importantly, this decision does not change our commitment to and investment in breast cancer. In addition, we began a Phase 3 study for selpercatinib for the treatment of adjuvant RET positive non-small cell lung cancer. And we also dosed the first patient in the U.S. trial of our Bcl-2 inhibitor. In Immunology, we announced positive top line data for our Phase 3 maintenance study of mirikizumab in ulcerative colitis.
We're pleased that the study met all primary and key secondary endpoints and we look forward to submissions in the first half of this year. We also announced positive top line Phase 3 results for lebrikizumab in combination with topical corticosteroids and we're encouraged that data to-date has demonstrated a competitive profile for treatment of atopic dermatitis. We await maintenance data for lebrikizumab in the first half of this year in advance of global submissions, which are expected by the end of 2022.
Moving to baricitinib, we announced last week that based on top line efficacy results from two Phase 3 trials we have decided to discontinue the Phase 3 development program for Lupus. For atopic dermatitis in the U.S., we're in ongoing discussions with the FDA but do not have alignment with the agency on the indicated population, which could possibly lead to a Complete Response Letter. We expect regulatory action for this indication, very soon.
Finally, we have submitted baricitinib for alopecia areata in the U.S. and hope it will become the first medicine approved for patients living with this disease later this year. In our early phase immunology portfolio we started a new Phase 1 study for CD-19 antibody we've discontinued our oral IL-17 inhibitor. Moving to neurodegeneration; in our early phase pipeline, we announced that we have received breakthrough therapy designation for N3pG4, an additional amyloid lowering agent for which we intend to initiate pivotal trials by the end of this year.
We have evidence that this therapy is completely and rapidly cleared amyloid plaque and we're exploring flexible dosing regimens, including subcutaneous dosing. For the treatment of Alzheimer's disease we also began a Phase 2 trial for our O-GlcNAcase inhibitor, an oral small molecule targeting Tau. While donanemab has been a primary focus for investors, we're pleased with the continued clinical advancement of the rest of our neurodegeneration pipeline. Now turning to donanemab; in December, we initiated two additional Phase 3 studies TRAILBLAZER ALZ 3, our prevention study for asymptomatic Alzheimer's disease in TRAILBLAZER ALZ 4 our head-to-head plaque clearance study compared to Aduhelm.
It's been less than one year since we published the positive randomized controlled TRAILBLAZER ALZ study, which demonstrated clinically meaningful benefits on endpoints of cognition and function. Since then we have focused investors on the need for replication from our well-designed expanded Phase 3 study TRAILBLAZER ALZ 2, which is now fully enrolled and expected to readout in mid-2023. While a lot has happened in this space during this last year and more events are likely before we get topline results next year, what hasn't changed for us is the importance of the TRAILBLAZER ALZ two readout and our confidence in both donanemab and the unique study design.
Given the impact of this devastating disease, we believe that if TRAILBLAZER ALZ 2 provides positive confirmatory data, we can see a scenario where there is not global reimbursement, patient access and broad use of donanemab. We noted last year that we had low expectations for the use of donanemab during the period between potential accelerated approval and the availability of confirmatory Phase 3 data in mid-2023. We're disappointed with the position that Centers for Medicare and Medicaid Services has taken in its draft National Coverage Determination decision and those low expectations could now extent for some months beyond the TRAILBLAZER ALZ 2 readout if reconsideration of CMS coverage determination is required given historical timelines for this process.
While the accelerated approval pathway was instituted by the FDA to allow for earlier approval of drugs to treat serious conditions and fill an unmet medical need and is providing valuable access to more patients faster than what is available under clinical trials, the NCD has currently written essentially negates that patient benefit in Alzheimer's disease. Still, we intend to complete our application for accelerated approval for donanemab yet this year, but we now move completion of the accelerated approval submission out of Q1.
We expect further volatility and expectations as competitor Alzheimer's disease trials readout prior to our definitive data. We remain confident the differentiation of donanemab and in our uniquely designed TRAILBLAZER ALZ 2 study, and importantly, the long-term opportunity to help patients with donanemab remains unchanged. Lastly, with respect to our progress with COVID-19 therapies, early this year we submitted a request to the FDA for emergency use authorization for bebtelovimab for treatment of mild to moderate COVID-19 for patients at high risk for progression to severe COVID-19 including hospitalization or death.
This is the third antibody we've developed for the treatment of COVID-19, an authentic virus and pseudo virus assays demonstrate that bebtelovimab retains neutralization activity against Omicron on as well as all other known variants of concern. We've produced several hundred thousand doses of bebtelovimab and stand ready to supply as needed if this antibody receives EUA from the FDA. In addition, we've also submitted a supplemental NDA for baricitinib for treatment of hospitalized patients with COVID-19 and expect regulatory action by the middle of this year.
Baricitinib currently has an EUA for this indication. We're proud of the therapies we've delivered to help combat the COVID-19 pandemic and we'll continue to do our part as public health needs emerge. In summary, Q4 was another productive quarter for R&D at Lilly capping what was an outstanding year of pipeline progress on behalf of patients.
Now, I'll turn the call back to Dave.
