Additionally, the study showed statistically significant improvements across all secondary endpoints for both the overall and monotherapy groups. These endpoints included key measures of disease progression such as the 6-minute walk test (6-MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and New York Heart Association (NYHA) Class at Month 30 (all with p<0.025). Notably, vutrisiran treatment also resulted in reduced all-cause mortality in the overall population (HR 0.645, p<0.025) and the monotherapy population (HR 0.655, p<0.05) up to Month 42. This analysis was pre-specified and intent-to-treat, incorporating up to six months of data from the open-label extension.
“I am thrilled with the outcomes of the HELIOS-B study, which indicate that vutrisiran could be a groundbreaking treatment for patients with ATTR amyloidosis with cardiomyopathy,” stated Yvonne Greenstreet, MBChB, CEO of Alnylam. “With a positive regulatory review, vutrisiran could become the new standard of care for this condition, propelling Alnylam into a new phase of significant growth.”
Comprehensive findings from the HELIOS-B study have been submitted as a late-breaking abstract to the European Society of Cardiology for presentation. The Company intends to initiate global regulatory submissions later this year, which includes submitting a supplemental New Drug Application to the FDA using a Priority Review Voucher.
Bristol Myers Squibb Secures FDA Nod for KRAZATI and Cetuximab in Advanced KRAS G12C Colorectal Cancer
Bristol Myers Squibb announced that the FDA has granted accelerated approval for KRAZATI ® (adagrasib) in combination with cetuximab. This treatment is targeted at adult patients with KRASG12C-mutated locally advanced or metastatic colorectal cancer (CRC), as identified by an FDA-approved test, who have previously been treated with chemotherapy regimens including fluoropyrimidine, oxaliplatin, and irinotecan. The approval is based on the objective response rate (ORR) and duration of response (DOR) results. Continued approval may depend on confirming clinical benefits in a follow-up trial.
The approval is based on results from cohorts of the Phase I/II KRYSTAL-1 open-label study, which evaluated KRAZATI (600 mg tablets taken orally twice daily) in combination with cetuximab in 94 patients with heavily pretreated colorectal cancer (CRC) carrying a KRASG12C mutation. The study achieved its primary endpoint, with a confirmed overall response rate (ORR) of 34% (n=94, 95% CI: 25-45) for KRAZATI combined with cetuximab, all of which were partial responses. The median duration of response (DOR), a secondary endpoint, was 5.8 months (95% CI: 4.2-7.6). Currently, late-line standard care options result in limited response rates (ORR 1-6%) after progression on chemotherapy with or without VEGF/VEGFR inhibitors.
“The recent approval of KRAZATI for CRC marks its second approval in the U.S. and the first within BMS’ newly expanded oncology portfolio. This milestone is significant for BMS and the patients we serve, reflecting our dedication to providing innovative cancer treatments,” stated Wendy Short Bartie, Senior Vice President of U.S. Oncology and Hematology at Bristol Myers Squibb. “We are proud to offer KRAZATI, the first FDA-approved KRASG12C inhibitor for conditions beyond non-small cell lung cancer, to CRC patients and are eager to continue evaluating its potential through our ongoing development program.”
In 2022, the FDA granted breakthrough therapy designation for KRAZATI in combination with cetuximab for patients with KRASG12C-mutated advanced CRC whose disease has progressed after previous treatments with specific chemotherapies and anti-VEGF therapy.
KRAZATI is an irreversible inhibitor of KRASG12C with a long half-life of 23 hours, dose-dependent pharmacokinetics, and the ability to penetrate the central nervous system. When used with cetuximab, it may enhance the inhibition of KRAS-dependent signaling or counteract adaptive feedback mechanisms.
The company has collaborated with QIAGEN to develop a tissue-based companion diagnostic (CDx) for KRAZATI, which is now available.
Japan Approves EZHARMIA® as First Dual EZH1/EZH2 Inhibitor for Peripheral T-Cell Lymphoma Treatment
Daiichi Sankyo’s EZHARMIA® (valemetostat tosilate) has been approved in Japan for treating adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This approval makes EZHARMIA the first dual inhibitor of EZH1 and EZH2 to be approved for PTCL, following its SAKIGAKE designation for this use.
PTCL is a rare and heterogeneous group of clinically aggressive types of non-Hodgkin lymphoma (NHL) that develop in mature white blood cells called “T cells” and “natural killer (NK) cells.” These represent a varied group of disorders making up 10% to 15% of non-Hodgkin lymphomas. The majority of PTCL subtypes, such as PTCL-NOS, AITL, ALCL, enteropathy-type T-cell lymphoma, and extranodal natural killer (NK) cell/T-cell lymphoma, are characterized by their aggressive nature. PTCLs are rare in the United States but more prevalent in Asia.
According to DelveInsight’s analysis, the total incident population of PTCL in the 7MM was reported to be ~26K in 2023. Specifically, within this figure, the incident population of PTCL patients in the United States was identified to be around 13K during the same year.
The Japan Ministry of Health, Labour and Welfare (MHLW) approved EZHARMIA based on the results of the VALENTINE-PTCL01 phase II trial, presented at the 2023 American Society of Hematology (ASH) Annual Meeting. In the VALENTINE-PTCL01 trial, EZHARMIA achieved an objective response rate (ORR) of 43.7% (n=52, 95% CI: 34.6-53.1) among 119 evaluable patients with relapsed or refractory PTCL, as determined by CT-based blinded independent central review (BICR). This included 17 complete responses (CRs) and 35 partial responses (PRs). Responses were observed across various PTCL subtypes, such as angioimmunoblastic T-cell lymphoma (AITL), PTCL not otherwise specified (PTCL-NOS), and other PTCL subtypes.
“This second approval for EZHARMIA in Japan marks a significant step forward in treating relapsed or refractory peripheral T-cell lymphoma, where there is a critical need for new and effective therapies to enhance patient outcomes,” stated Toshinori Agatsuma, PhD, Executive Officer and Head of the R&D Division in Japan at Daiichi Sankyo. “EZHARMIA showcases Daiichi Sankyo’s pioneering research efforts dedicated to developing new medications that have the potential to transform the standard of cancer care.”
In VALENTINE-PTCL01, the safety characteristics of EZHARMIA were similar to those observed in earlier clinical studies. Out of 133 patients, 106 (79.7%) experienced adverse events related to treatment, with the most frequent being decreases in platelet count (44.4%), anemia (27.1%), dysgeusia (24.8%), and neutrophil count (21.1%).
Vertex Reports Encouraging Findings From Phase I/II VX-880 Trial for Type 1 Diabetes at ADA’s 84th Scientific Sessions
Vertex Pharmaceuticals Incorporated shared new findings from its Phase I/II clinical trial of VX-880, a prospective therapy derived from stem cells and fully developed islet cells, for individuals with type 1 diabetes (T1D) who experience impaired awareness of hypoglycemia and severe hypoglycemic events (SHEs). The updated results concerning 12 patients who underwent a complete dosage via a single infusion in Parts B and C of the trial align with earlier positive outcomes reported in the VX-880 trial. These findings underscore the promising impact this therapy could have in transforming diabetes treatment.
VX-880 has been largely well received. Most adverse events were mild or moderate, and there were no serious adverse events attributed to VX-880 treatment. Two patient deaths occurred, as previously noted, but neither were linked to VX-880 treatment. Overall, the safety profile aligns with the immunosuppressive regimen, infusion procedure, and complications associated with long-standing diabetes, as reported earlier.
Carmen Bozic, M.D., Vertex’s Executive Vice President of Global Medicines Development and Medical Affairs, and Chief Medical Officer, expressed that the new data further support VX-880 as a promising treatment for T1D. She highlighted their approval to increase study participants as they prepare for pivotal development, aiming to bring this potentially transformative therapy to patients eagerly awaiting it.
Piotr Witkowski, M.D., Ph.D., Professor of Surgery and Director of the Pancreatic and Islet Transplant Program at the University of Chicago Medicine, and a member of Vertex’s VX-880 Steering Committee, expressed enthusiasm about the study findings: “The data we’ve observed so far in this research are incredibly promising. Stem cell-derived islets manage blood glucose levels as effectively as natural human islets. Significant improvements have been noted in several key measures of glycemic control, including the elimination of severe hypoglycemic episodes and reduced or eliminated reliance on external insulin. These outcomes have the potential to bring about profound changes in the treatment of Type 1 diabetes, offering hope for alleviating the substantial burden this disease places on patients.”
The findings were shared at the American Diabetes Association’s 84th Scientific Sessions Conference on June 21, 2024, in Orlando, Florida, as part of an invited presentation titled ‘Update on Clinical Trials Using Stem Cell Replacement’ during the ADA/IPITA symposium, held from 3:45 to 5:15 p.m. ET.
argenx Receives FDA Approval for VYVGART Hytrulo to Treat Chronic Inflammatory Demyelinating Polyneuropathy
argenx SE has reported that the FDA approved VYVGART Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) to treat adults with chronic inflammatory demyelinating polyneuropathy (CIDP). This medication is administered once weekly via a 30-to-90-second subcutaneous injection. Notably, VYVGART Hytrulo marks the first and sole neonatal Fc receptor (FcRn) blocker endorsed for CIDP treatment.
Luc Truyen M.D., Ph.D., Chief Medical Officer at argenx, expressed the company’s commitment to translating scientific advancements into practical solutions for patients suffering from severe autoimmunity. He highlighted that patients have long awaited new treatments, and today, argenx has delivered the first innovative treatment for CIDP in over three decades. VYVGART Hytrulo, described as a precision tool, has demonstrated significant benefits for patients. The FDA approval marks a transformative new treatment option for CIDP patients and reinforces the therapeutic efficacy of VYVGART Hytrulo, showcasing the potential of FcRn blockade in treating IgG-mediated autoimmune diseases.
The FDA approval of VYVGART Hytrulo is supported by findings from the ADHERE Study, the largest clinical trial conducted to date on CIDP. In this study, 69% of patients treated with VYVGART Hytrulo showed clinical improvement, encompassing gains in mobility, function, and strength, regardless of prior treatment history. The ADHERE study successfully achieved its primary endpoint (p<0.0001), demonstrating a 61% decrease (HR: 0.39, 95% CI: 0.25; 0.61) in the risk of relapse compared to placebo. Nearly all trial participants (99%) chose to continue in the ADHERE open-label extension phase. Safety outcomes were generally consistent with the established safety profile of VYVGART from earlier clinical trials and real-world usage.
Furthermore, VYVGART Hytrulo has been approved in the United States for the treatment of generalized myasthenia gravis (gMG) in adult patients who test positive for anti-acetylcholine receptor (AChR) antibodies.
