James Bradner
Executive Vice President, Research & Development & Chief Scientific Officer at Amgen
Thank you, Vikram, and good afternoon, everyone. In the second quarter, we rapidly advanced our broad clinical pipeline of potentially first-in-class or best-in-class programs. We received two approvals in the quarter, a breakthrough therapy designation, and delivered exciting clinical data for many programs, while eagerly awaiting additional data readouts later this year.
Let's begin with general medicine. As previously mentioned, based on the interim analysis, we are seeing a differentiated profile with MariTide and are confident it will address important unmet medical needs in obesity, obesity-related conditions and Type II diabetes. We remain on-track and look forward to top-line 52-week data from the ongoing 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 diabetes, along with a Phase 2 trial investigating MariTide for the treatment of diabetes in patients with and without obesity.
Beyond MariTide, we continue to progress at our early obesity programs that consist of both oral and injectable in creatine and non-creatine approaches. We expect one of these programs to enter clinical development later this year. Also, in gen-med is Olpasiran, our potentially best-in-class LPa targeting small interfering RNA medicine. The fully enrolled Phase 3 cardiovascular outcomes trial of Olpasiran continues to progress. To remind LPa is a genetically defined cardiovascular risk factor that is elevated in approximately 20% of individuals and for whom no effective or targeted therapies currently exists.
In oncology, we continue to deliver on high conviction targets with differentiated therapies capable of delivering transformative clinical benefit for patients. Let's begin with IMDELLTRA, our first-in-class bispecific T-cell engager or BiTE molecule targeting DLL3 for small cell lung cancer. We're very pleased that the FDA granted that accelerated approval to IMDELLTRA for the treatment of adult patients with extensive stage small cell lung cancer with disease progression on or after platinum-based chemotherapy. Further, we are pleased that the NCCN guidelines have been updated to include IMDELLTRA as a preferred option for patients with a chemotherapy free interval less than or equal to six months, and as an other recommended treatment option for patients with a chemotherapy-free interval greater than six months. Based on the remarkable activity observed as a single agent in patients receiving second and third-line therapy, we are rapidly advancing IMDELLTRA into frontline therapy with three Phase 3 studies underway in both extensive and limited stage disease. One of these studies, DeLLphi-304, our confirmatory Phase 3 study in second-line small cell lung cancer has completed enrollment.
Notably, IMDELLTRA is the first bispecific T-cell engager approved to treat a common solid tumor. The present study of tarlatamab in earlier lines and in the context of lower tumor burden draws from our experience with our first approved bispecific T-cell engager BLINCYTO and B-cell acute lymphoblastic leukemia. Here we observed a dramatic improvement in overall survival and minimal residual disease negative patients, along with improved tolerability. These BLINCYTO data provide evidence that directing the T-cell in this manner is an effective means of finding and eliminating residual cancer cells that are drivers of recurrence. This June, based on the profound survival benefit observed in the treatment of frontline disease, the FDA approved an additional indication for BLINCYTO for the treatment of adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome negative B-cell ALL in the consolidation phase of treatment here regardless of minimal residual disease status. We continue to seek to expand the impact of BLINCYTO in newly diagnosed B-ALL through ongoing studies and with the further investigation of subcutaneous administration.
Our first-in-class STEAP1 CD3 bispecific molecule Xaluritamig has also demonstrated profound clinical activity in metastatic castrate-resistant prostate cancer, importantly demonstrating our ability to target a second common solid tumor with a bispecific T-cell engager therapy. We are rapidly advancing this program and have now fully enrolled the monotherapy Phase 1 dose expansion as we continue to enroll patients and reduce monitoring in outpatient cohorts. Further, we are advancing the study of Xaluritamig earlier in the prostate cancer treatment paradigm with combinations of xaluritamig and enzalutamide or abiraterone ongoing while we plan additional studies in earlier disease settings. In sum, we regard IMDELLTRA, BLINCYTO, Xaluritamig as major advances further establishing the broad potential of our leading bispecific T-cell engager platform.
To round out oncology, we have completed enrollment of FORTITUDE-101, a Phase 3 study of Bemarituzumab, a first-in-class fibroblast growth factor receptor 2b directed monoclonal antibody administered in combination with chemotherapy in front-line gastric cancer. We are also rapidly advancing AMG 193, our oral PRMT5 inhibitor developed for MTAP-null solid tumors as both a monotherapy and in combination with other therapies. Additional data from the Phase 1 dose escalation and initial dose expansion study of AMG 193 in patients with MTAP-null solid tumors will be presented at ESMO in September. Lastly, we are pleased also to share that the FDA has granted an orphan drug designation to AMG 193 for the treatment of pancreatic cancer.
Turning to inflammation. We are encouraged by the data arising from our Phase 2 study of TEZSPIRE in patients with moderate to very severe COPD. Together with AstraZeneca, we are actively planning for Phase 3 development in COPD. We are also pleased to announce that the FDA recently granted TEZSPIRE a breakthrough therapy designation as an add-on maintenance treatment of patients with moderate to very severe COPD characterized by eosinophilic phenotype. Beyond COPD, we continue to explore TEZSPIRE in separate Phase 3 studies in eosinophilic esophagitis and in chronic rhinosinusitis with nasal polyps where top-line data are expected later this year.
Turning to Rocatinlimab, a first-in-class T-cell rebalancing monoclonal antibody targeting the OX40 receptor. The comprehensive Rocatinlimab Phase 3 ROCKET program has successfully enrolled over 3,100 patients with moderate to severe atopic dermatitis. Five of the eight studies are now fully enrolled. The Phase 3 HORIZON study, part of this ROCKET program evaluates Rocatinlimab monotherapy versus placebo in adults with moderate to severe atopic dermatitis, and it is ongoing with data readout anticipated in H2. Beyond atopic dermatitis, we continue to explore the potential of Rocatinlimab in additional indications and have initiated a Phase 2 study in moderate to severe asthma as well as a Phase 3 study in prurigo nodularis.
Shifting to rare disease. We are encouraged by the advancements of our rare disease pipeline with several mid to late-stage opportunities. UPLIZNA, a CD19 B-cell depleting therapy offers a differentiated mechanism of action than other autoimmune therapies, durable efficacy with a convenient every six-month IV dosing schedule. This could be very important for chronic inflammatory diseases. Recently, we were excited to announce positive topline results from a Phase 3 clinical trial evaluating the efficacy and safety of UPLIZNA for the treatment of Immunoglobulin G4-related disease. The trial met its primary endpoint, showing an astonishing 87% reduction in the risk of IgG4-related disease flare as compared to placebo during the 52-week placebo-controlled window. All key secondary endpoints were also met, and no new safety signals were identified. This is the first randomized control trial to demonstrate efficacy in the IgG4-related disease patient population. Regulatory filing activities are underway and full data from the trial will be presented at a future medical meeting.
We are also studying UPLIZNA in generalized myasthenia gravis through the ongoing Phase 3 MINT study. The MINT study is evaluating the efficacy and safety of UPLIZNA in patients with generalized myasthenia gravis, who are of a comparable disease severity and a comparable treatment experience to other recently approved biologic therapies. We are investigating UPLIZNA in the two predominant antibody serotypes that drive this disease, acetylcholine receptor positive and in muscle specific tyrosine kinase positive patients. MINT is the only trial attempting to demonstrate efficacy while removing the treatment benefit of steroids. Patients in the MINT trial who entered on steroids had a protocol specified taper by 24 weeks. We look forward to data readout in the second half of 2024.
To expand the impact of our CD19 directed therapeutics to even more patients suffering from serious inflammatory diseases compelled by both biological inferences and insights from small studies of CD19 directive therapies, we are launching a development program targeting CD19 positive B-cell mediated autoimmune disease with UPLIZNA and Blinatumomab. This is an exciting and promising space with Amgen's strong capabilities and inflammatory disease and two well-characterized assets, we are very well positioned to lead in this rapidly advancing field. We will have more to say about these programs in due course.
Lastly, in May, the FDA approved BKEMV as the first interchangeable biosimilar to Soliris or Eculizumab. Also, in biosimilar development, registration-enabling studies are underway for ABP 234, a biosimilar candidate to Keytruda and ABP 206 a biosimilar candidate to OPDIVO.
In closing, I'd like to thank my Amgen colleagues for their strong sense of service to patients facing serious illness, their intense focus and spirited collaboration during this momentous year and their commitment to growing the impact of both our research and our business through this portfolio of potential first-in-class and best-in-class medicines.
I'll now turn it over to Peter.
