Alnylam Gets Positive CHMP Advisories for Vutrisiran in ATTR Cardiomyopathy Treatment

Alnylam Pharmaceuticals has received a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) for its RNA interference (RNAi) therapy, Vutrisiran, to treat both wild-type and hereditary transthyretin amyloid cardiomyopathy (ATTR-CM). This recommendation is based on the results of the phase III HELIOS-B clinical trial, which demonstrated significant reductions in mortality and cardiovascular events, while also maintaining patients' functional status and quality of life. Clinical Trial Results The HELIOS-B trial involved approximately 642 patients with ATTR-CM and was a randomized, double-blind, placebo-controlled study conducted at multiple centers globally. The trial reached all its predetermined primary and secondary endpoints, showing that Vutrisiran can rapidly and continuously reduce the levels of transthyretin (TTR) protein in the blood. This reduction helps slow the progression of the disease by preventing abnormal TTR accumulation in heart tissue. Patients treated with Vutrisiran experienced a 30% lower risk of cardiovascular death and hospitalization compared to those in the placebo group. Additionally, the drug improved functional capabilities, measured by the six-minute walk test, and overall health status, assessed through the Kansas City Cardiomyopathy Questionnaire. These improvements were consistent across all patient subgroups, including those already receiving TTR stabilizers. The trial also showcased Vutrisiran's safety profile, with the most common side effects being pain, arthralgia, dyspnea, injection site reactions, and elevated serum alkaline phosphatase and alanine aminotransferase levels. Patients need to supplement their vitamin A intake during treatment due to Vutrisiran lowering serum vitamin A levels. Regulatory Progress Vutrisiran has already been approved in the United States by the Food and Drug Administration (FDA) on March 20, 2023, and in Brazil by the National Health Surveillance Agency (ANVISA) on March 31, 2023. The CHMP's positive opinion paves the way for a final decision by the European Commission, expected in June 2025. If approved, Vutrisiran will be the first RNAi therapy specifically designed for ATTR-CM in the European market, offering a more convenient quarterly subcutaneous injection option compared to current treatments, which often require frequent infusions. Background on ATTR-CM ATTR-CM is a rare and progressive disease characterized by the accumulation of misfolded TTR proteins in heart tissue, leading to impaired cardiac function. Symptoms often include heart failure and severe arrhythmias, and the disease is particularly prevalent among older adults. Many cases go undiagnosed or are identified late, significantly impacting patients' ability to receive timely treatment. Vutrisiran targets the production of TTR protein, aiming to halt disease progression and improve patient outcomes. Company Actions and Future Plans Alnylam Pharmaceuticals plans to present detailed findings from the HELIOS-B trial at the European Society of Cardiology (ESC) Congress, scheduled from August 30 to September 2, 2024. The company also intends to share these results at other international cardiology conferences. Beyond ATTR-CM, Alnylam has submitted additional applications for Vutrisiran to regulatory bodies in Japan and is preparing to submit further applications globally in 2025. Company Profile and Industry Impact Alnylam Pharmaceuticals, founded in 2002 and headquartered in Cambridge, Massachusetts, is a pioneering biopharmaceutical company in the field of RNAi therapeutics. The company's mission is to translate Nobel Prize-winning science into viable medical solutions for genetic and rare diseases. Alnylam's portfolio includes several late-stage drug candidates, including Onpattro®, which received FDA approval in 2018 for treating hereditary transthyretin amyloidosis (hATTR) polyneuropathy. The development and potential approval of Vutrisiran are seen as significant milestones for Alnylam. Dr. Pushkal Garg, Chief Medical Officer of Alnylam, commented, "The positive opinion from CHMP is a critical acknowledgment of the value Vutrisiran brings to patients. We remain committed to bringing this potentially transformative therapy to a broader audience." Industry Reactions and Implications Industry experts have welcomed the CHMP's positive recommendation, noting that Vutrisiran could become a standard treatment for ATTR-CM. The drug's ability to effectively reduce TTR production and its convenient dosing schedule make it an attractive option for both physicians and patients. This milestone is expected to further accelerate the development and application of RNAi therapies in treating other rare diseases. The success of Vutrisiran underscores Alnylam's leadership in the RNAi therapy space and demonstrates the therapeutic potential of RNAi technology in addressing challenging medical conditions. With this positive momentum, Alnylam is poised to make significant contributions to the field of biotechnology and continue its mission of developing life-changing medicines. Conclusion Vutrisiran's positive CHMP recommendation represents a major breakthrough in the treatment of ATTR-CM, offering a novel and effective RNAi-based solution. The drug's proven benefits in reducing mortality and improving patient quality of life highlight its transformative potential. As Alnylam continues to advance the global approval process, the company remains a leader in RNAi technology, contributing significantly to the evolution of therapeutic approaches for rare diseases.