Michael E. Severino
Vice Chairman and President at AbbVie
Thank you, Jeff.
I'll start with immunology, where we had several notable pipeline events in the quarter. In the area of inflammatory bowel disease, we reported positive top-line results from the Phase 3 maintenance studies for Rinvoq in ulcerative colitis and Skyrizi in Crohn's disease.
In the Rinvoq UC maintenance study, both the 15 and 30 milligram doses, met the primary and all secondary endpoints at week 52. In the induction portion of the program, Rinvoq demonstrated a very strong impact on the disease. And the results from this maintenance study demonstrate that patients continuing treatment with Rinvoq maintain a high levels of clinical remission, clinical response and endoscopic improvement at the one-year mark. In fact, maintenance treatment with either dose of Rinvoq resulted in some of the highest rates of remission and endoscopic improvements seen in UC clinical studies. With the 30 milligram Rinvoq dose, 52% of patients achieved clinical remission, 62% achieved endoscopic improvement, 49% achieved histologic-endoscopic mucosal improvement, and 68% achieved steroid-free remission.
We are very pleased with how Rinvoq performed from a safety perspective as well. In this maintenance study, the exposure adjusted event rates for overall adverse events, including serious and severe events, were higher in the placebo group than in either Rinvoq dose group. Additionally, the exposure adjusted rates for MACE, VTE and malignancies, excluding non-melanoma skin cancer, were comparable between Rinvoq groups and placebo. These results provide further evidence that Rinvoq has the potential to become a highly-effective therapy for patients with moderate to severe ulcerative colitis.
We're also nearing completion of the Crohn's disease program for Rinvoq and expect to see data from the first Phase 3 induction study later this year. Results from the second induction study and the maintenance study are expected in the first half of next year, with regulatory submissions also anticipated in 2022.
We also saw very impressive results from Skyrizi in the maintenance phase of our Crohn's disease program, particularly with the 360 milligram maintenance dose, which met the co-primary endpoints of clinical remission and endoscopic response versus the withdrawal arm at week 52. Importantly, when we look at the most stringent endpoints, we see strong separation between Skyrizi 360 milligrams and control, with the response rates of 39% for endoscopic remission and 29% for deep remission, compared to 13% and 10% for the withdrawal group at week 52.
We remain on track to submit our regulatory applications for Rinvoq in UC and Skyrizi in Crohn's in the coming months.
In the quarter, we also announced updates regarding our regulatory applications for Rinvoq in atopic dermatitis, psoriatic arthritis and ankylosing spondylitis. In June, Rinvoq received a positive CHMP opinion in Europe, recommending both the 15 milligram and 30 milligram doses in moderate to severe atopic dermatitis. This CHMP opinion puts us on track for a European approval in August. When approved, atopic dermatitis will be the fourth indication for Rinvoq in Europe.
Regarding our supplemental NDAs in the US, we recently announced that we were notified by the FDA that they would not need our PDUFA action dates for Rinvoq in psoriatic arthritis, ankylosing spondylitis and atopic dermatitis, which were in late June for psoriatic arthritis and AS and mid July for atopic dermatitis. The agency cited their ongoing review of the tofacitinib, ORAL Surveillance study, indicated that they -- indicating that they needed more time to complete their reviews of the data. The FDA has not requested any additional safety analysis for Rinvoq since the PDUFA dates were missed. While there are no new action dates, based on our discussions with the agency, we expect decisions on our regulatory applications in the next few months, following completion of the agency's review of the tofacitinib, ORAL Surveillance data. We remain confident in the benefit risk profile for Rinvoq across all indications and we'll continue to work with the FDA to bring Rinvoq to market in these new disease areas.
In our early stage immunology pipeline, we recently began to new trials for ABBV-154, our TNF steroid conjugate. We initiated a definitive dose-ranging study in patients with RA and also started our Phase 2 study in polymyalgia rheumatica. Later this year, we expect to begin the Phase 2 study for 154 in Crohn's disease.
Also in the quarter, we completed the induction stage of a Phase 2 proof-of-concept study evaluating Ravagalimab in ulcerative colitis patients. While the CD40 antagonist demonstrated greater efficacy compared to historical control, the efficacy results did not meet our pre-specified criteria. As a result, we will not be advancing Ravagalimab in ulcerative colitis.
In oncology, we continue to make good progress across all stages of our pipeline. At the recent ASCO and EHA meetings, data were presented from the GLOW and CAPTIVATE studies, evaluating a fixed duration Imbruvica and Venclexta regimen in CLL patients. Results from these two studies demonstrated that the all oral fixed-duration Imbruvica plus Venclexta regimen has the potential to provide deeper and more durable remission and extend progression-free survival as a frontline treatment across the spectrum of age and fitness status for CLL patients. We plan to submit these data to regulatory agencies and look forward to bringing this new fixed duration treatment option to CLL patients once approved.
Earlier this month, we received a breakthrough therapy designation for Venclexta in combination with Azacitidine for previously untreated higher risk MDS patients, based on the strong data demonstrated thus far in our ongoing Phase 1b study. We expect to see final results from this study in the coming months and plan to discuss the data with regulators regarding the potential to support an accelerated approval for Venclexta in MDS.
Also in the quarter, we saw interim results from a Phase 1 study evaluating the BCMA CD3 bispecific antibody TMB-383B in multiple myeloma patients who have received at least three prior lines of therapy. 383 performed very well as a monotherapy in these heavily pre-treated patients, demonstrating an objective response rate of nearly 80% and a very good partial response or better rate of 63% and a complete response rate of nearly 30% at doses greater than 40 milligrams in the dose escalation cohort.
Based on these promising results, we exercised our right to acquire TMB-383B from Teneobio. We expect the transaction to close in the coming months. And we'll provide more information on our development plan for 383 in multiple myeloma later this year. This is a highly competitive area. But based on the data to date, we believe this BCMA CD3 bispecific has the potential to be differentiated on the efficacy, safety and dosing interval, and could be best in class as both a monotherapy and combination therapy across lines of treatment in multiple myeloma.
We continue to make good progress with the navitoclax program in myelofibrosis, which consists of randomized Phase 3 trials in both the frontline and relapsed refractory setting, as well as a single-arm Phase 2 study. Based on feedback from the FDA, we intend to submit our regulatory application with randomized Phase 3 data together with the Phase 2 trial results. We expect the Phase 3 data readout and regulatory submissions in the second half of 2022, with Navitoclax approval in myelofibrosis anticipated in 2023.
In neuroscience, we recently completed the Phase 2 proof-of-concept studies for two assets: Elezanumab in multiple sclerosis and ABBV-8E12 in Alzheimer's disease. In their respective studies, neither asset met the efficacy endpoints of the trial, and we will be discontinuing the development of Elezanumab in MS and 8E12 in Alzheimer's disease.
Given the enormous unmet need in Alzheimer's disease, we remain committed to finding disease modifying therapies and we continue to pursue a range of approaches. We have several additional programs that are either in the clinic today or are in preclinical development. These include programs that modulate the neuro inflammatory response in Alzheimer's disease, such as our TREM2 and CD33 programs that are both in clinical development. And programs that target pathologic [Indecipherable] through novel mechanisms, such as approaches that target intracellular aggregates for clearance that are in preclinical development.
Following the accelerated approval of Aducanumab in the US, there has been an increased focus on A-beta directed programs. We have monitored this area closely over the last several years, and based on all of the available data, we believe there is a continued opportunity for an A-beta directed monoclonal antibodies that clears plaque more rapidly than existing agents, with a reduced risk of amyloid-related imaging abnormalities or ARIA. We have profiled a number of A-beta antibodies preclinically and we have a candidate with the potential to meet these requirements. We expect to introduce this candidate into the clinic by the end of this year or early next year.
Also in neuroscience, we're nearing completion of our registrational program for ABBV-951 in advanced Parkinson's disease. We recently completed an interim analysis in the first of two Phase 3 studies where our subcutaneous levodopa/carbidopa delivery system demonstrated safety and efficacy comparable to Duopa after six months of treatment. The primary objective of this trial was safety, but efficacy was also evaluated as secondary endpoints. In this analysis, 951 performed very well, demonstrating a 52% reduction in normalized off-time and a 41% increase in normalized on-time without troublesome dyskinesia. Patients also benefited from 951's 24-hour continuous levodopa/carbidopa infusion, with patients experiencing substantial benefits in sleep and reduction in morning off-time. Full data from the six-month interim analysis will be presented at a medical meeting later this year. Data from a second Phase 3 study are expected in the fourth quarter, with our regulatory submissions anticipated later this year or early next year.
And lastly, in Eye Care, at the recent meeting for the American Society for Cataract and Refractive Surgery, we presented results from the Phase 3 GEMINI 1 study, evaluating our topical eye drop AGN-190584 for the treatment of symptoms associated with presbyopia. In this study, 584 demonstrated improved near vision without impacting distance vision, with a rapid onset of action within 15 minutes and sustained vision improvements for up to 6 hours. 584 has the potential to be convenient on-demand solution for patients with mild to moderate presbyopia and we look forward to an approval decision later this year.
So, in summary, we've made great progress with our pipeline in the first half of this year and we look forward to several additional data readouts, regulatory submissions and approvals throughout the remainder of 2021.
With that, I'll turn the call over to Rob for additional comments on our second quarter performance and financial outlook. Rob?
