Alnylam Secures Positive CHMP Recommendation for Vutrisiran in Treating ATTR Amyloidosis with Cardiomyopathy
In a significant regulatory milestone for RNA interference (RNAi) therapeutics, Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the industry leader in RNAi-based drug development, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of its RNAi therapeutic vutrisiran for the treatment of wild-type or hereditary transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM) in adults.
This development marks a critical step forward for Alnylam and its efforts to expand the clinical reach of vutrisiran, a once-quarterly administered RNAi therapy already approved in the European Union under the brand name AMVUTTRA® for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy. If approved by the European Commission, vutrisiran would become the first and only RNAi therapeutic available in Europe for the treatment of ATTR-CM, a severe and progressively debilitating form of transthyretin amyloidosis that primarily affects the heart.
Understanding ATTR-CM: A Devastating and Often Overlooked Condition
Transthyretin amyloidosis (ATTR) is a systemic, progressive disease caused by the deposition of amyloid fibrils derived from misfolded transthyretin (TTR) protein. In ATTR-CM, these fibrils accumulate in cardiac tissue, leading to thickening and stiffening of the heart walls, reduced cardiac function, arrhythmias, and eventual heart failure. Left untreated, ATTR-CM is typically fatal within a few years of diagnosis.
The condition can be classified as either hereditary (hATTR-CM), resulting from TTR gene mutations, or wild-type (wtATTR-CM), which occurs due to age-related changes in the TTR protein and typically affects older adults. ATTR-CM is frequently misdiagnosed or diagnosed late due to its nonspecific symptoms, which can resemble other cardiovascular conditions, such as hypertensive heart disease or hypertrophic cardiomyopathy.
Importantly, treatment options for ATTR-CM remain limited. Tafamidis, a TTR stabilizer, is currently the only approved therapy in the EU specifically for ATTR-CM, and while it slows disease progression, it does not eliminate TTR production at the source. This leaves a significant unmet medical need for therapies that can more effectively modify the disease process.
Vutrisiran: A New Generation RNAi Therapeutic with Cardioprotective Potential
Vutrisiran is a next-generation RNAi therapeutic designed to silence the gene responsible for the production of transthyretin in the liver. By targeting the mRNA that encodes TTR, vutrisiran reduces circulating TTR levels, thereby lowering the substrate available for amyloid fibril formation. The drug employs Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate platform, allowing targeted delivery to hepatocytes via subcutaneous injection.
The treatment is administered quarterly, offering a convenient dosing schedule that may enhance patient adherence and quality of life. Moreover, vutrisiran’s subcutaneous administration route supports flexibility in care, with options for healthcare professional administration or self-administration by patients or caregivers—a meaningful advantage for patients with limited mobility or access to specialized centers.
“This positive CHMP opinion marks another important milestone in our efforts to bring vutrisiran to people around the world living with ATTR amyloidosis with cardiomyopathy,” said Pushkal Garg, M.D., Chief Medical Officer at Alnylam. “In the HELIOS-B study, vutrisiran treatment resulted in rapid knockdown of TTR and led to improved survival, fewer hospitalizations and less disease progression in patients with ATTR-CM, nearly half of whom were on a TTR stabilizer.”
HELIOS-B: Landmark Phase 3 Data Underpinning CHMP Opinion
The CHMP’s recommendation is based on robust clinical data from the HELIOS-B Phase 3 trial, a global, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of vutrisiran in patients with both wild-type and hereditary ATTR-CM.
The HELIOS-B study enrolled over 650 patients and assessed multiple clinically meaningful endpoints related to survival, cardiac function, physical performance, and quality of life. The trial met all ten pre-specified primary and secondary endpoints across the overall and monotherapy populations. This comprehensive efficacy profile highlights vutrisiran’s potential as a disease-modifying agent in ATTR-CM.
Key findings from HELIOS-B include:
- Reduction in all-cause mortality and fewer cardiovascular hospitalizations, underscoring the therapy’s life-extending potential.
- Improved functional capacity, as measured by the 6-minute walk test (6MWT), indicating better physical endurance.
- Enhanced quality of life, demonstrated by improvements in the Kansas City Cardiomyopathy Questionnaire (KCCQ).
- Slowed progression of heart failure symptoms, reflected in stable or improved New York Heart Association (NYHA) functional class scores.
- Consistent therapeutic benefit across subgroups, including patients taking concomitant TTR stabilizers such as tafamidis.
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Equally important, vutrisiran exhibited a favorable safety profile. The rates of adverse events (AEs), serious AEs, and AEs leading to drug discontinuation were similar between treatment and placebo groups. Common side effects included mild injection site reactions and transient elevations in liver enzymes such as alkaline phosphatase and alanine transaminase. No new safety signals emerged, reinforcing the therapy’s manageable risk-benefit profile.
Full results from HELIOS-B were recently published in The New England Journal of Medicine, further validating the scientific rigor and clinical impact of the findings.
A Growing Global Footprint: Regulatory Approvals and Submissions
The CHMP’s recommendation follows recent international regulatory successes for vutrisiran. The therapy was approved in the United States by the Food and Drug Administration (FDA) on March 20, 2025, and subsequently by Brazil’s National Health Surveillance Agency (ANVISA) on March 31, 2025 for the treatment of ATTR-CM. These approvals extend vutrisiran’s therapeutic reach beyond its initial indication in hATTR polyneuropathy.
In addition, vutrisiran is currently under review by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), and Alnylam has expressed intentions to pursue additional global submissions in 2025 and beyond. The company’s global regulatory strategy reflects a commitment to making RNAi-based therapies available to patients across diverse healthcare systems and geographies.
Alnylam’s Broader Vision for RNAi in Rare and Cardiometabolic Diseases
Vutrisiran’s potential expansion into ATTR-CM represents a broader strategic shift for Alnylam as it seeks to transition from a pioneering RNAi platform company into a fully integrated global biopharmaceutical enterprise. ATTR-CM lies at the intersection of rare disease and cardiology, areas in which Alnylam is actively building therapeutic franchises.
The success of vutrisiran also exemplifies the growing maturity of RNAi therapeutics as a viable and scalable drug modality. Since the first RNAi approval in 2018 (patisiran), Alnylam has steadily advanced a pipeline of gene-silencing medicines targeting a range of conditions, including primary hyperoxaluria, acute hepatic porphyria, hypercholesterolemia, and hypertension.
As Dr. Garg emphasized, “Combined with its quarterly dosing and well-established safety profile, we believe vutrisiran could offer an important new treatment option for patients in the EU.” The company’s continued investment in innovation, manufacturing, and global access infrastructure is positioning RNAi as a cornerstone technology in precision medicine.
Next Steps and Outlook
With the CHMP’s positive opinion now in hand, the European Commission is expected to make a final decision on vutrisiran’s approval for ATTR-CM within the coming months. A formal approval would enable Alnylam to launch vutrisiran across EU member states for this new indication, opening access to thousands of patients who currently face limited treatment options.
In the broader context of amyloidosis treatment, the potential approval of vutrisiran for ATTR-CM could reshape clinical practice by offering physicians a mechanism-based alternative to TTR stabilizers. As RNAi therapeutics continue to evolve and gain Alnylam acceptance, they may become foundational tools for treating protein misfolding disorders and other genetically defined diseases.
With its growing portfolio, expanding geographic footprint, and focus on high unmet medical needs, Alnylam is poised to remain a dominant force in the RNAi landscape—and the anticipated approval of vutrisiran for ATTR-CM in Europe may be one of the most impactful regulatory moments in the field to date.
