Jay Bradner
Executive Vice President, Research and Development, and Chief Scientific Officer at Amgen
Thank you, Vikram, and good afternoon, everyone.
In the third quarter, we made significant progress advancing our broad clinical pipeline, which includes a number of potentially first-in-class or best-in-class therapies. Since our last update, we have initiated a Phase 2 study of MariTide in type 2 diabetes and delivered positive potentially practice-changing Phase 3 data with UPLIZNA in generalized myasthenia gravis. Additionally, the FDA granted Breakthrough Therapy Designation for UPLIZNA in IgG4-related diseases underscoring the important potential impact of this medicine.
We also showcased promising data from several oncology programs at major medical conferences, including IMDELLTRA, xaluritamig, and AMG-193, while reporting positive results from the first of eight Phase 3 studies evaluating rocatinlimab in atopic dermatitis.
Let's begin with general medicine. As previously mentioned, based upon the interim analysis of the ongoing Phase 2 study of MariTide in chronic weight management, we are seeing a differentiated profile and are confident MariTide will address important unmet medical needs in obesity, obesity-related conditions in type 2 diabetes. We remain on track and look forward to top line 52-week data from the MariTide Phase 2 study in late 2024.
We are actively planning and expect to initiate a broad Phase 3 program in obesity, obesity-related conditions and type 2 diabetes. This quarter, we initiated a dedicated Phase 2 trial investigating MariTide in patients with type 2 diabetes, living with and without obesity. MariTide has the potential to be the first therapy in this setting with monthly or even less frequent dosing. Beyond MariTide, our Phase 1 trial of AMG-513 is actively enrolling patients. We also continue to advance our preclinical obesity programs, which include both oral and injectable approaches comprising both incretin and non-incretin mechanisms.
Also in general medicine is olpasiran, our potentially best-in-class Lp (a) targeting small interfering RNA medicine. The fully enrolled Phase 3 cardiovascular outcomes trial of olpasiran continues to progress.
In oncology, IMDELLTRA, a first-in-class bispecific T cell engager or BiTE molecule, targeting DLL3 for small cell lung cancer is rapidly advancing into earlier lines of therapy with three Phase 3 studies underway in both extensive stage and limited stage disease. To further enhance the patient experience, we are evaluating reduced monitoring protocols as part of the Phase 3 program, and we have initiated a Phase 1b study evaluating subcutaneous tarlatamab in patients with second line or later extensive-stage small cell lung cancer. In September, we presented impressive follow-up data from our Delphi 301 Phase 2 study of IMDELLTRA in patients with extensive stage small cell lung cancer, demonstrating sustained anticancer activity and a manageable safety profile. We also presented data from Delphi 303, the Phase 1b study of IMDELLTRA combined with a PD-L1 inhibitor as maintenance therapy following four cycles of chemotherapy in first-line extensive-stage small cell lung cancer. This design is similar to our ongoing Phase 3 study, Delphi 305, which test the efficacy of IMDELLTRA in PD-L1 inhibition versus PD-L1 inhibition alone, in first-line extensive-stage small cell lung cancer, following platinum-based chemotherapy. With a median follow-up of 10 months, IMDELLTRA has demonstrated a manageable safety profile, median duration of disease control of 9.3 months, median progression-free survival of 5.6 months and a nine-month estimated overall survival of 89%.
Moving to our first-in-class Steep 1 CD3 bispecific molecule, xaluritamig, we are pleased to announce that following consultation with regulatory authorities, we will initiate a Phase 3 study in post-taxane metastatic castrate-resistant prostate cancer, or mCRPC, this quarter. The promise of xaluritamig was recently evidenced by data presented in September from a Phase 1 dose exploration cohort evaluating monotherapy in patients with mCRPC. With a median follow-up of 27.9 months, the median overall survival was 17.7 months across all cohorts, a potential improvement upon the historical median survival of 12 to 15 months in this patient population.
Additional data from a Phase 1 randomized dose expansion and optimization cohort has identified the recommended dose and schedule for Phase 3 clinical investigation. Additionally, we are studying xaluritamig in earlier lines of therapy in combination and in earlier stages of prostate cancer. Our Phase 1 study of xaluritamig in combination with enzalutamide and abiraterone, is ongoing. Recently, we have initiated two additional Phase 1b studies investigating xaluritamig in the upfront management of more localized disease. The first study evaluates neoadjuvant accelerated therapy that is prior to radical prostatectomy in patients with newly diagnosed, localized, intermediate or high-risk prostate cancer. The second study evaluates xaluritamig in high-risk nonmetastatic hormone-sensitive prostate cancer after definitive therapy. We are particularly excited about the potential of xaluritamig, now our third bispecific T cell engager entering late-stage clinical development.
Beyond our T cell engagers, we have completed enrollment of FORTITUDE 102, a Phase 3 study of bemarituzumab, our first-in-class fibroblast growth factor receptor IIb directed monoclonal antibody combined with chemotherapy and nivolumab in first-line gastric cancer. In the coming months, we expect to read out the results of FORTITUDE 101, a Phase 3 study of bemarituzumab combined with mFOLFOX6 chemotherapy versus chemotherapy alone in first-line gastric cancer. This study was designed based on the successful Phase 2 FIGHT study, which reported numerically longer progression-free survival and overall survival.
Lastly, we are also rapidly advancing AMG 193, our oral PRMT5 inhibitor developed for MTAP NOL solid tumors. We recently initiated a Phase 2 study of AMG 193 in patients with MTAP NOL previously treated advanced non-small cell lung cancer. This study will help to address regulatory agency requirements for dose optimization and selection. In September, we presented encouraging data from a Phase 1 dose escalation and initial dose expansion study, demonstrating promising monotherapy activity and an acceptable safety profile.
Turning to inflammation. Based upon encouraging Phase 2 data from TEZSPIRE in patients with COPD, we are planning to initiate Phase 3 studies in collaboration with AstraZeneca. These trials will target patients with moderate to very severe COPD with blood eosinophil counts greater than or equal to 150 cells per microliter. We expect to begin enrollment in the first half of 2025. TEZSPIRE is also being investigated in separate Phase 3 studies of patients with eosinophilic esophagitis and in chronic rhinosinusitis with nasal polyps, where top line data are expected later this year.
In September, we announced positive results from the Phase 3 Horizon study of rocatinlimab in atopic dermatitis. The study met its co-primary endpoints and all key secondary endpoints. We anticipate additional data readouts from the ROCCAT program will deepen our understanding of rocatinlimab's profile. Beyond atopic dermatitis, we continue to explore rocatinlimab in moderate to severe asthma and prurigo nodularis.
To expand the impact of our CD19 directed therapeutics for even more patients suffering from serious inflammatory diseases, we have initiated Phase 2 studies of blinatumomab, our CD19 targeting BiTE molecule approved as BLINCYTO and inebilizumab, our CD19 targeting monoclonal antibody approved as UPLIZNA. These studies build on mounting evidence of therapeutic benefit for B-cell depletion in autoimmune diseases from small investigator-sponsored trials of blinatumomab in systemic sclerosis and refractory rheumatoid arthritis. Our initial focus will be on systemic lupus erythematosus with nephritis with plans to expand into additional indications.
Shifting to rare disease. We recently presented potentially practice-changing results from the Phase 3 MINT study, the largest placebo-controlled trial for a biologic therapy in generalized myasthenia gravis. MINT evaluated UPLIZNA in both a acetylcholine receptor autoantibody positive ACHR-positive and muscle-specific kinase autoantibody positive or MuSK-positive populations. At the reported 26-week time point, UPLIZNA demonstrated clinically meaningful and statistically significant improvements in the myasthenia gravis activities of daily living score after just two doses compared to placebo. This efficacy was observed in the combined ACHR and MuSK-positive populations as well as in each population separately. UPLIZNA also achieved statistically significant improvements in the quantitative myasthenia gravis score, compared to placebo at week 26 in the combined populations.
Importantly, in the MINT study, patients taking corticosteroids were tapered down starting at Week 4 to a five-milligram per day dose by Week 24. MINT is the first and only Phase 3 placebo-controlled myasthenia gravis trial for a biologic that tapered corticosteroid use. As such, the efficacy observed with UPLIZNA in patients with generalized myasthenia gravis offers a chance for meaningful benefit without the burden and toxicity of chronic steroid use. We look forward to 52-week data for the ACHR positive cohort and results from both ACHR positive and MuSK-positive patient populations, in the open-label period of the MINT study where UPLIZNA has the potential to demonstrate durable efficacy.
Moving beyond generalized myasthenia gravis in August, the FDA granted UPLIZNA Breakthrough Therapy Designation for the treatment of immunoglobulin GI-related diseases, or IgG4-related disease based upon data from the Phase 3 MITIGATE study. This data will be presented at the American College of Rheumatology Conference in November. We are extremely encouraged by the potential of UPLIZNA in both myasthenia gravis and IgG4-related disease and are actively working to file these data with regulatory authorities.
In closing, I want to thank my Amgen colleagues for their unwavering commitment to patients facing grievous illnesses for the focus for the collaboration during this productive year.
I'll now turn it over to Peter for the financial update.
