Alnylam Reports Success in Heart Drug Study

An experimental medication developed by Alnylam Pharmaceuticals has shown promising results in treating patients with transthyretin amyloidosis cardiomyopathy, a severe heart disease. In a recent clinical trial, participants treated with Alnylam's drug, vutrisiran, demonstrated a 28% lower risk of death from any cause or recurrent cardiovascular event compared to those given a placebo. Among participants who were not already taking Pfizer's drug, tafamidis, at the start of the study, vutrisiran showed a 33% reduction in risk versus placebo. These outcomes were crucial goals of the study after Alnylam made statistical adjustments to its design in February.

Vutrisiran, which is marketed as Amvuttra for a different form of the disease, also showed significant improvements in secondary heart health measures. The trial further revealed that vutrisiran reduced the risk of death by 36% in the overall study population over a 42-month period, and by 35% in participants not on tafamidis. The benefits of the treatment were consistent across various subgroups, including those with different levels of disease severity.

The trial results indicated no significant differences in adverse events, serious adverse events, or side effects leading to study discontinuation between the drug and placebo groups. Alnylam noted that no adverse events were more common by 3% or more in the vutrisiran group compared to the placebo group. However, full details of the trial have yet to be disclosed, with comprehensive data expected to be presented at the European Society of Cardiology meeting later this month.

Alnylam plans to submit these results to regulatory authorities for approval and intends to use a priority review voucher to expedite the evaluation process. CEO Yvonne Greenstreet expressed optimism about vutrisiran's potential to become the new standard of care for treating ATTR amyloidosis with cardiomyopathy, thereby driving substantial growth for Alnylam.

The positive trial results have sparked optimism among analysts. Stifel analyst Paul Matteis suggested that vutrisiran could become a blockbuster drug in the TTR-cardiomyopathy market. Alnylam's shares surged nearly 40% in pre-market trading, reaching levels not seen since late 2022.

This development comes as a much-needed boost for Alnylam, which has faced financial challenges despite its pioneering work in RNA interference drug development. The company has brought four rare disease drugs to market and discovered a cholesterol-lowering medication sold by Novartis but struggled with consistent profitability, recording significant losses in recent years.

Success with vutrisiran in treating transthyretin amyloidosis cardiomyopathy could mark a turning point for Alnylam. The company already markets vutrisiran and a similar drug, Onpattro, for the rarer polyneuropathy form of the disease, but the cardiomyopathy variant is more prevalent. Alnylam estimates that over 250,000 people worldwide suffer from this form of the disease, compared to 30,000 to 50,000 in the U.S. and Europe with polyneuropathy. Pfizer's tafamidis, the only approved drug for cardiomyopathy, generated $3.3 billion last year, making it a top-selling medication.

Alnylam has aimed to surpass Vyndamax, Pfizer's tafamidis, initially with Onpattro and now with vutrisiran. Although Onpattro showed success in a Phase 3 study in 2022, the FDA rejected its application, prompting Alnylam to abandon plans for its approval in cardiomyopathy. Meanwhile, a similar drug developed by BridgeBio Pharma has also shown promise in testing and could receive FDA approval by November.

Vutrisiran, which is administered via subcutaneous injection, differs from Onpattro, which requires infusion. Unlike the shorter Onpattro study, vutrisiran's trial duration was sufficient to evaluate its long-term benefits, such as extending life and preventing hospital stays, similar to the criteria supporting Vyndamax's approval.

Analysts have high expectations for vutrisiran, given the performance of Onpattro in clinical testing and the potential superiority of RNA interference therapies over oral medicines like those from Pfizer and BridgeBio. These oral drugs stabilize the misfolded protein transthyretin, while RNA interference therapies prevent its production.

The debate over the best treatment approach continues, but Alnylam's recent results may intensify the discussion. BridgeBio's drug showed a 25% reduction in the risk of death and a 50% reduction in hospitalizations in its Phase 3 trial. However, comparing results across different studies can be challenging due to varying patient demographics. Nonetheless, vutrisiran appears poised to become a leading treatment option, potentially serving as both a second-line and first-line therapy.

The next major development in the TTR cardiomyopathy treatment landscape is expected in 2025, with results anticipated from a Phase 3 study of another silencer drug, eplontersen, being developed by AstraZeneca and Ionis Pharmaceuticals. Additionally, Intellia Therapeutics and Regeneron are testing a gene editing treatment for the disease.