AMVUTTRA Transforms ATTR-CM Treatment: FDA Green Light for First Therapy Addressing Both Cardiomyopathy and Polyneuropathy

Alnylam Pharmaceuticals’ RNAi therapeutic AMVUTTRA (vutrisiran) has secured FDA approval for treating the cardiomyopathy manifestation of transthyretin-mediated amyloidosis (ATTR-CM), marking a watershed moment in managing this progressive cardiac condition. The drug now holds a unique position as the only FDA-approved therapy tackling both ATTR-CM and hereditary polyneuropathy (hATTR-PN) in adults.

Clinical Evidence Reshapes ATTR-CM Outlook

The HELIOS-B Phase 3 trial demonstrated AMVUTTRA’s capacity to alter disease trajectory fundamentally. Across all 10 pre-specified endpoints, the therapy achieved statistical significance compared to placebo. Most notably, the drug reduced all-cause mortality and recurrent cardiovascular events by 28% during the double-blind treatment window spanning up to 36 months. Extended analysis through 42 months revealed a striking 36% mortality reduction in the overall population.

For patients receiving AMVUTTRA monotherapy, the impact proved even more pronounced. The therapy cut mortality risk by 35% and reduced all-cause/recurrent cardiovascular events by 33% during the double-blind phase. Patients experienced tangible functional improvements: preserved exercise capacity, maintained quality-of-life measures, and early biomarker improvements in NT-proBNP and troponin I—markers historically predictive of cardiovascular deterioration.

Understanding ATTR-CM: The Disease Landscape

ATTR-CM represents a devastating, rapidly progressive condition affecting approximately 150,000 Americans and over 300,000 patients globally. Two forms exist: hereditary ATTR affecting ~50,000 worldwide, and wild-type ATTR impacting 200,000-300,000 individuals. The disease stems from misfolded transthyretin proteins accumulating as amyloid deposits, progressively damaging cardiac and neurological tissues. Currently, most patients remain undiagnosed, and many who receive standard therapies continue experiencing disease progression. No cure exists, leaving patients facing irreversible cardiac damage and premature mortality.

The RNAi Mechanism: Addressing Disease at Its Source

AMVUTTRA operates through RNA interference, silencing the TTR gene that produces disease-causing transthyretin proteins. This upstream intervention rapidly depletes TTR production, substantially reducing amyloid fibril deposition and halting the irreversible cardiac damage cascade. Administered via four convenient subcutaneous doses annually, AMVUTTRA offers a simplified treatment regimen compared to conventional approaches. Dr. Ronald Witteles, HELIOS-B investigator and Stanford University cardiologist, emphasizes that “vutrisiran’s mechanism allows patients to live longer, experience fewer hospitalizations, and improve their functional capacity—outcomes rarely seen in ATTR-CM management.”

Patient Access and AMVUTTRA Cost Considerations

Affordability represents a critical barrier in rare disease treatment. Alnylam has structured broad insurance coverage for AMVUTTRA, with approximately 99% of hATTR-PN patients achieving coverage, and the majority paying zero out-of-pocket expenses. Comparable coverage dynamics and payer acceptance are anticipated for ATTR-CM patients, given the robust clinical value demonstrated in HELIOS-B.

The company’s Alnylam Assist program removes additional access hurdles. This in-house support system provides one-on-one patient navigation, insurance coordination, financial assistance, and a Quick Start program offering eligible patients their initial AMVUTTRA dose at no cost if coverage delays occur. These integrated support structures aim to minimize AMVUTTRA cost burden and ensure seamless treatment initiation.

Safety Profile and Tolerability

AMVUTTRA’s safety foundation rests on extensive real-world experience: over 5,000 patient-years of global exposure through the earlier HELIOS-A trial and approved use across 15+ countries for hATTR-PN treatment. The most frequently observed adverse reactions included extremity pain (15%), arthralgia (11%), dyspnea (7%), and vitamin A level reductions (7%). Importantly, HELIOS-B identified no novel safety signals in ATTR-CM patients, maintaining the established safety framework.

Patients require vitamin A supplementation at recommended daily allowance levels, as AMVUTTRA treatment lowers serum vitamin A. Ophthalmologic evaluation is recommended if patients develop symptoms suggestive of vitamin A deficiency, such as night blindness.

Global Regulatory Pathways Advancing

Marketing authorization applications are currently under European Medicines Agency (EMA), Brazilian Health Regulatory Agency (ANVISA), and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) review. Alnylam anticipates proceeding with additional global regulatory submissions throughout 2025, expanding AMVUTTRA’s availability to international ATTR-CM populations.

The Clinical Community’s Perspective

Muriel Finkel, President of Amyloidosis Support Groups, characterized the approval as “a significant moment for patients living with ATTR amyloidosis,” representing hope for a community historically limited by treatment options and diminished quality-of-life outcomes. Medical leadership echoes this sentiment, viewing AMVUTTRA’s cardiovascular mortality reduction and functional preservation as meaningful advances in an unmet medical space.

Alnylam’s two-decade partnership with the ATTR amyloidosis community continues evolving through innovation-driven clinical development, positioning AMVUTTRA as a potential care standard for patients facing this life-limiting disease.