Alnylam CEO Highlights Major Success for Amvuttra in Key Heart Disease Trial

In a significant development for Alnylam Pharmaceuticals, the company reported that its RNA interference drug, Amvuttra (vutrisiran), significantly reduced the risk of death and recurrent cardiovascular events in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This announcement marks a pivotal point for Alnylam, as it seeks to solidify its position as a leading biopharmaceutical company.

During the HELIOS-B trial, Amvuttra demonstrated a 28% reduction in the risk of death or recurrent cardiovascular events compared to placebo in the overall ATTR-CM patient population. This includes patients who were also receiving Pfizer’s tafamidis, a standard treatment for ATTR-CM, for up to 36 months. Notably, for the 60% of participants who were not on tafamidis—sold under the commercial names Vyndaqel and Vyndamax—Amvuttra reduced the risk of death or cardiovascular events by 33%.

The trial also achieved statistical significance across several secondary endpoints, including improvements in the six-minute walk test, the Kansas City Cardiomyopathy Questionnaire (KCCQ), and the New York Heart Association (NYHA) classification at month 30.

Alnylam's CEO, Yvonne Greenstreet, emphasized that these results not only affirm the efficacy of Amvuttra but also showcase the potential of RNA interference as a therapeutic mechanism. Greenstreet noted that the trial outcomes support Amvuttra's position as a new standard of care for ATTR-CM.

Analysts reacted positively to the trial results, even as they sought more detailed data about the combination of Amvuttra and tafamidis. William Blair analyst Myles Minter, Ph.D., highlighted the drug's effectiveness in both naïve and tafamidis-experienced patients, suggesting broad applicability.

The HELIOS-B readout was particularly anticipated as it could determine Alnylam's continued leadership in RNA interference therapy, following the FDA's refusal to approve its previous ATTR drug, Onpattro, for ATTR-CM. Amvuttra is already approved for hereditary ATTR-polyneuropathy, a condition affecting the nervous system, and Alnylam estimates ATTR-CM to be ten times more prevalent.

The expansion of Amvuttra's label to include ATTR-CM is seen as a significant milestone. Alnylam's chief medical officer, Pushkal Garg, M.D., pointed out that the trial showed clear benefits in reducing the risk of death, which is a crucial metric for patients and physicians given the severe prognosis of ATTR-CM.

In terms of administration, Amvuttra is given via subcutaneous injection every three months, which may offer convenience compared to the daily oral dose required for tafamidis. This dosing schedule could also potentially lower out-of-pocket costs for patients.

Despite the promising results, some uncertainties remain, particularly regarding the specific data on the combination of Amvuttra and tafamidis. Alnylam's chief commercial officer, Tolga Tanguler, mentioned that payers might only cover monotherapy treatments for ATTR-CM in the near future, given the high costs of both drugs.

The HELIOS-B trial's success in various secondary endpoints further reinforces Amvuttra's potential as a leading treatment for ATTR-CM. Alnylam has submitted the detailed results to the European Society of Cardiology and plans to seek regulatory approvals later this year, including using a priority review voucher for its FDA application.

These developments underscore the transformative potential of Amvuttra in treating ATTR-CM and highlight Alnylam’s advancements in RNA interference therapies.