James Bradner
Executive Vice President, Research and Development, and Chief Scientific Officer at Amgen
Thank you, Bob, and good afternoon, everyone. Let me start with MariTide. Reiterating Bob's comments, we are very pleased with the results seen with MariTide thus far. And we're very pleased with the overall conduct of the ongoing Phase II trial. All arms remain active, patient dropout has not been an issue, and we're fully on track for top line 52-week data from this 11-arm Phase II study in late 2024. We're seeing a differentiated profile of MariTide and are confident that it will address important unmet medical needs, obesity, obesity-related conditions and diabetes. We look forward to completing the ongoing Phase II study and working with regulators to move rapidly to the broad Phase III program. Later this year, we plan to initiate an additional dedicated Phase II trial investigating MariTide for the treatment of diabetes in patients with and without obesity. This new trial is not a gating step for our Phase III program in patients with obesity. Informed by dose and schedule insights from the ongoing Phase II obesity study, the dedicated Phase II study in diabetes conforms to regulatory requirements for Phase III and is the next step towards a diabetes indication for MariTide. In terms of patient experience, we expect to deliver MariTide in a convenient, handheld, patient-friendly auto-injector device with a monthly or even less frequent single-injection administration, assuming eventual approval. Across the portfolio, we are presently prioritizing differentiated medicines, those that stand to provide the greatest benefit for patients. Given the profile we've seen with AMG 786, we will not pursue further development. Instead, in obesity, we're differentially investing in MariTide and a number of preclinical assets.
Beyond MariTide, in the first quarter, we rapidly advanced our diverse clinical pipeline of potentially first-in-class or best-in-class programs. Looking ahead, the remainder of 2024 promises to be an exciting time for research and development with 2 PDUFA dates in June for tarlatamab in small cell lung cancer and BLINCYTO in adult acute lymphoblastic leukemia as well as 5 Phase III data readouts. Each of these milestones could represent a significant advance towards our mission to deliver groundbreaking treatments to patients in real need. Moving to olpasiran. We're pleased to announce that we've completed enrollment of the OCEAN(a)-Outcomes trial, a Phase III cardiovascular outcome study of olpasiran, our potentially best-in-class Lp(a)-targeting small interfering RNA medicine. Reflecting both our commitment to patients suffering from cardiovascular disease and the strong interest of the medical community, we successfully enrolled 7,297 patients across the globe in just 15.5 months. To our knowledge, this is the fastest-enrolling Phase III outcome study of its size. And to remind, Lp(a) is a genetically defined cardiovascular risk factor, which is elevated in approximately 20% of individuals and for whom no effective or targeted therapies currently exist. In oncology, we continue to deliver on high-conviction targets with differentiated therapies capable of delivering a large effect size for patients. Starting with tarlatamab, a first-in-class BiTE molecule targeting DLL3 for small cell lung cancer. We remain on track with an FDA priority review for a June 12 PDUFA date. We're excited about tarlatamab as potentially the first selective therapy for small cell lung cancer. Based on the remarkable activity observed as a single agent in patients receiving second and third-line therapy, we are rapidly advancing tarlatamab in a frontline treatment with 3 Phase III studies now initiated in both extensive stage and limited stage disease.
The rationale for studying tarlatamab in earlier lines of the context of lower tumor burden draws from our experience with BLINCYTO in B-cell ALL. There, we saw a dramatic improvement in overall survival in minimal residual disease-negative patients. These BLINCYTO data provide evidence that directing the T-cell in this manner is an effective means of finding and eliminating residual cancer cells, which are primarily the drivers of recurrent disease. We're hopeful we can build on this insight with tarlatamab, where comparable activity in early-stage small cell lung cancer patients would very meaningfully improve outcomes for patients facing the challenge of this aggressive cancer. In sum, we regard tarlatamab as a major advance as the first bispecific T-cell engager to demonstrate efficacy in a common solid tumor, further establishing the broad potential of our bispecific T-cell engager platform. Our first-in-class STEAP1 CD3 bispecific molecule, xaluritamig, has also demonstrated unambiguous activity in the solid tumor, namely prostate cancer, continues to advance following a presentation of encouraging Phase I data last fall. We have now fully enrolled the monotherapy Phase I dose expansion and continue to enroll patients in reduced monitoring and outpatient cohorts. Further, combination studies with xaluritamig in novel hormonal therapies are progressing in dose escalation studies with near-term plans to initiate dose expansion cohorts. To round out oncology, we are rapidly advancing AMG 193, our oral PRMT5 inhibitor targeting MTAP null solid tumors. We've moved forward with monotherapy dose expansion studies and have initiated 2 additional Phase I studies targeting MTAP null tumors in thoracic, gastrointestinal, biliary tract and pancreatic cancers, exploring relevant combinations with standard of care. In our inflammation portfolio, we are encouraged by the results of the COURSE Phase IIa proof-of-concept study, which investigated TEZSPIRE in patients with moderate to very severe COPD.
This study was designed to test TSLP inhibition across an intentionally broad range of eosinophil levels, irrespective of inflammatory drivers, emphysema, chronic bronchitis and smoking status. While TEZSPIRE achieved a clinically meaningful 17% reduction in the annualized rate of moderate or severe COPD exacerbations compared to placebo, this result fell short of statistical significance likely owing to the broad overall patient demographic. However, even greater reductions in COPD exacerbations were observed in a planned subgroup of patients with baseline blood eosinophil counts greater than 150 cells per microliter with a trend for further reduction in a small number of subjects with baseline counts greater than 300. We're excited by these data, which will be presented in an oral session of the American Thoracic Society Annual Meeting later this month. Together with our partner, AstraZeneca, we are actively planning for Phase III development of TEZSPIRE in COPD. Beyond COPD, we continue to explore TEZSPIRE in separate Phase III studies in eosinophilic esophagitis and chronic rhinosinusitis with nasal polyps, where top line data are expected in the second half of this year. The ROCKET Phase III program for rocatinlimab, a first-in-class anti-OX40 monoclonal antibody, has successfully enrolled over 2,800 patients with moderate to severe atopic dermatitis. Indeed, 3 of the 8 studies in the rocatinlimab ROCKET study program are now fully enrolled. The Phase III Horizon study, part of this ROCKET program, evaluates rocatinlimab monotherapy versus placebo in adults with moderate to severe atopic dermatitis and remains on track for top line data readout in the second half of this year.
Beyond atopic dermatitis, we continue to broadly explore rocatinlimab in additional indications and have initiated a Phase II study in moderate to severe asthma with plans to initiate a Phase III study in prurigo nodularis in the second half of this year. We're encouraged by the advancements of our rare disease pipeline as well with several mid- to late-stage opportunities. Starting with UPLIZNA, we anticipate important Phase III data readouts this year in myasthenia gravis and IgG4-related disease, both diseases with significant unmet need and where we have the potential to make a real difference for patients. Dazodalibep, an innovative CD40 ligand inhibitor fusion protein, has entered Phase III for Sjogren's disease with 2 studies now enrolling patients. This follows encouraging Phase II data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. Dazodalibep is the first therapy to demonstrate efficacy in the latter patient population. Lastly, in our biosimilars portfolio, we've initiated a Phase III study of ABP 234, a biosimilar candidate to KEYTRUDA, in subjects with advanced or metastatic non-squamous non-small cell lung cancer. We're also pleased to announce that WEZLANA, our biosimilar candidate to STELARA, has received a positive CHMP opinion. In closing, I'd like to thank my Amgen colleagues for their strong sense of service to patients facing serious illness and their commitment to growing the impact of both our research and our business to our portfolio of potential first-in-class and best-in-class medicines.
And I'll now turn it over to Murdo.
