Michael E. Severino
Vice Chairman and President at AbbVie
Thank you, Jeff. We made significant advancement across all stages of our pipeline in 2021, and we expect continued progress again this year. In immunology, we had several recent important regulatory updates. We implemented safety and indication updates to our RA label for Rinvoq and also received FDA approval in psoriatic arthritis and atopic dermatitis, securing strong labels that highlight Rinvoq's favorable benefit-risk profile in both new indications. In atopic dermatitis, we received approval for both the 15 milligram and 30 milligram doses, and based on the impressive levels of skin clearance and itch reduction demonstrated in our development program, we believe Rinvoq will be an important new treatment option for adult and adolescent patients with moderate-to-severe atopic dermatitis who have not responded well to other systemic agents such as cyclosporine, methotrexate, azathioprine or biologics.
We also have regulatory applications under review for Rinvoq in ulcerative colitis, ankylosing spondylitis, and non-radiographic Axial SpA. We expect an FDA approval decision next month for ulcerative colitis, in the second quarter for ankylosing spondylitis, and in the fourth quarter for non-radiographic Axial SpA. In Europe, we anticipate approval decisions for ulcerative colitis and non-radiographic Axial SpA in the second half of the year. We're nearing completion of Rinvoq's registrational program in Crohn's disease, which is the last major indication expansion program for Rinvoq. We recently announced positive top line results from the first phase 3 Crohn's induction study where Rinvoq demonstrated a very strong impact on clinical remission and endoscopic response in a difficult to treat refractory patient population. We expect to see results from the second phase 3 Crohn's induction study and from the maintenance study in the first half of this year, with regulatory submissions anticipated in the second half of 2022. Also in immunology, we recently received FDA approval for Skyrizi in psoriatic arthritis, an important indication expansion for this asset. Based on the strong joint efficacy and the high level of skin clearance that Skyrizi provided in our registrational trials, we believe Skyrizi will be very competitively positioned as an effective new treatment option for psoriatic arthritis patients.
We also have regulatory applications under review for Skyrizi in Crohn's disease with approval decisions expected in the U.S. next month and in Europe later this year. We've seen impressive results in our Crohn's disease program, and we believe Skyrizi has the potential to become an important new therapy in this market where there continues to be considerable unmet need. We're making very good progress with our early-stage immunology pipeline as well where we are developing novel agents with the goal of significantly advancing the standard-of-care across our core areas by providing deeper and more durable responses. Our anti-TNF steroid ADC ABBV-154 is a novel approach for delivering a potent steroid that has the potential to provide durable remission in diseases such as RA, PMR, and Crohn's disease. We expect to see preliminary data from our phase 2 dose-ranging study in RA in the fourth quarter of this year. We also expect to see phase 2 proof-of-concept data in PMR and Crohn's disease in 2023. In dermatology, our early-stage efforts are focused on developing oral agents that can provide clear skin with durable responses. Our RoR gamma T inverse agonist, ABBV-157, is designed to more effectively inhibit IL-17 production compared to pure antagonists which has the potential to result in a greater impact on skin inflammation. We recently began a phase 2 dose-ranging study for ABBV-157 in psoriasis.
Moving to oncology where we continue to make good progress across all stages of our pipeline. We recently received an FDA Breakthrough Therapy Designation for Teliso-V in second-line plus advanced or metastatic non-squamous, non-small cell lung cancer based on the encouraging results we've seen to date in our clinical program. Treatment options for patients who have exhausted platinum-based chemotherapy, immunotherapy, and targeted therapy are limited to single agent chemo which typically provides response rates of only 15% to 20% with a median overall survival of less than one year. Prognosis for these patients is very poor. While targeted therapies have been approved by the FDA for the 3% to 4% of non-small cell lung cancer patients harboring MET exon 14 skipping mutations, there are currently no therapies approved specifically for the much larger group of patients who exhibit c-Met protein overexpression. Patients with overexpressed c-Met represent about 25% to 30% of the advanced or metastatic non-squamous, non-small cell lung cancer population with wild type EGFR, which corresponds to an incidence of approximately 35,000 patients each year in the U.S.
In stage one of our phase 2 study, we saw promising efficacy in heavily pretreated patients who received Teliso-V, including a 54% objective response rate in those with highly expressed c-Met. The second stage of the phase 2 study is ongoing and has the potential to support an accelerated approval in second line plus advanced metastatic, non-squamous, non-small cell lung cancer. We expect to see additional data from this study next year. We also recently began the clinical program for our next-generation c-Met ADC, ABBV-400, which utilizes a more potent topoisomerase inhibitor payload to potentially drive deeper tumor responses in patients with both intermediate and high levels of c-Met expression.
We also expect to see data this year from several important indication expansion programs for Venclexta, including results from the phase 3 CANOVA trial in relapse refractory multiple myeloma patients with a t(11;14) mutation, as well as results from our program for Venclexta in previously untreated higher-risk MDS patients where we received a breakthrough therapy designation. We plan to submit our regulatory applications to the FDA in the first half of this year for an accelerated approval in MDS and late in '22 or early '23 for multiple myeloma. Both indications represent important expansion opportunities for Venclexta and will help drive long-term growth for our oncology portfolio.
We are also making very good progress with epcoritamab where we continue to generate strong data in early-stage studies to support our view that epcoritamab has the potential to become a differentiated and best-in-class CD3XCD20 bispecific across several B cell malignancies, including diffuse B cell and follicular lymphomas. We'll see monotherapy data in the third quarter from the phase 2 expansion cohort in DLBCL which has the potential to support a submission for accelerated approval in the second half of this year. We also have a phase 3 study ongoing in third-line relapse refractory DLBCL, and we plan to initiate several additional phase 3 trials this year, including studies in earlier lines of therapy for diffuse B cell lymphoma in multiple combinations, as well as in follicular lymphoma in combination with Rituximab and Revlimid. This year we'll also see additional data maturing from our cohort expansion studies for ABBV-383, both as a monotherapy and in combinations with standard-of-care and novel agents in multiple myeloma. We believe our BCMA CD3 bispecific has the potential to be differentiated on efficacy, safety, and dosing interval, and can be best-in-class across multiple lines of therapy. We plan to initiate phase 3 studies later this year in relapse refractory multiple myeloma.
We also continue to make good progress with Navitoclax in myelofibrosis where we've seen strong mid-stage data supporting our view that Navitoclax has the potential to provide disease modification, which we believe will lead to improved and durable clinical outcomes for patients. We expect a phase 3 data readout and regulatory submissions in the first half of next year with approval anticipated near the end of 2023.
Moving to neuroscience where we expect several important pipeline events in 2022 as well. We recently completed discussions with the FDA and are preparing to submit our application for Vraylar as an adjunctive treatment for major depressive disorder. Based on the totality of the data and the strong benefit-risk profile demonstrated in our clinical program, we believe Vraylar has the potential to be competitively positioned as an adjunctive treatment for major depressive disorder. We expect a submission in the first quarter and an approval decision by the end of the year.
We've also completed our registration-enabling program for ABBV-951, our novel subcutaneous levodopa/carbidopa delivery system for treatment of advanced Parkinson's disease. In our phase 3 studies, ABBV-951 proved superior to oral levodopa/carbidopa in reducing motor fluctuations in this advanced population, and we believe our innovative new delivery system represents a potentially transformative improvement to current treatment options. We remain on track to submit our regulatory applications in the first half of this year in the U.S. and Europe with both approval decisions anticipated in early 2023. And we expect to see phase 3 data for Qulipta in chronic migraine prevention later in the first quarter and plan to submit our regulatory applications in both the U.S. and Europe this summer with approval decisions expected in the first half of 2023.
So, in summary, we remain focused on continuing to execute on our pipeline programs and anticipate numerous important regulatory and clinical milestones across all stages of our pipeline in 2022. This includes important indication expansion for on-market drugs and data readouts and regulatory actions for key late-stage assets, as well as proof-of-concept data from several early-stage NME programs.
With that, I'll turn the call over to Rob for additional comments on our fourth quarter performance and our 2022 financial outlook. Rob?
