Alnylam May Rival Pfizer in ATTR-CM, Experts Seek Complete Data

Topline results from a Phase III trial of Alnylam’s RNAi therapy Amvuttra in treating ATTR amyloidosis with cardiomyopathy have garnered significant attention. The trial demonstrated a statistically significant reduction in all-cause mortality and recurrent cardiovascular events.

Kostas Biliouris, director and equity research analyst at Bank of Montreal Capital Markets, was optimistic about the results, stating they exceeded initial expectations and might represent a best-case scenario. Nevertheless, a comprehensive understanding will emerge once the full data set is released later this summer. Further insights from the HELIOS-B study will be shared at the European Society of Cardiology’s congress in London from August 30 to September 2.

Paul Matteis, head of the therapeutics research team at Stifel, emphasized that the absence of detailed data is one of the primary unanswered questions currently. Amvuttra faces competition from Pfizer’s ATTR-CM oral drugs, Vyndamax and Vyndaqel, which were approved in 2019. The Vyndaqel family has achieved blockbuster status, generating $1.1 billion in sales in the first quarter of 2024, a 66% increase from the same period in 2023.

In the HELIOS-B trial, Amvuttra reduced the risk of mortality and recurrent cardiovascular events by 28% in patients also taking Pfizer’s Vyndamax compared to a placebo. For those only on Amvuttra, the risk reduction was 33%. The secondary endpoint, the risk of death from all causes, showed a 36% reduction in patients taking both drugs and a 35% reduction in those on Amvuttra alone. Additionally, patients on Amvuttra demonstrated significant improvements in metrics like the six-minute walk test.

Biliouris suggested that, based on the current data, Amvuttra could be among the best treatments for ATTR cardiomyopathy. Matteis also noted that Amvuttra might be at least tied for the top spot among treatments but highlighted the importance of the 30-month data to provide a complete comparison with Vyndamax and BridgeBio’s investigational drug acoramidis.

Despite the promising results, some experts are skeptical about Amvuttra’s ability to compete with Pfizer. Myles Minter, a research analyst at William Blair, indicated that Alnylam has more work to do. He pointed out that Vyndamax is a safe drug with an impressive hazard ratio, and the patient population in Amvuttra’s clinical trials had more severe cardiovascular events than those typically prescribed the drug today. Minter emphasized the need for more control data against placebo in the current patient population and suggested that the detailed data expected at the European Society of Cardiology’s congress will clarify Amvuttra’s competitiveness.

Financially, Amvuttra is currently approved only for polyneuropathy, generating over $900 million in sales and growing 18% year over year from a patient population of between 30,000 and 60,000. Minter believes the cardiomyopathy opportunity could expand Amvuttra’s patient base tenfold as more noninvasive diagnostic techniques become available for ATTR-CM. He estimates peak sales of $3.7 billion in the U.S. and $1.8 billion in the EU, while Matteis projects peak drug sales of around $5 billion to $6 billion. However, Vyndamax is expected to maintain its blockbuster status.

Pricing will also play a significant role in Amvuttra’s financial outlook. Currently priced higher than Vyndamax, there is an expectation of price adjustments. Matteis added that economic drivers like the potential for practices to earn more through in-office injections could also influence Amvuttra’s market position. While there is potential for Alnylam to lead, definitive conclusions await the full data.