Alnylam drug approval brings cardiomyopathy competition to Pfizer, Bridgebio Pharma

Alnylam Pharmaceuticals has identified a long-awaited FDA decision that extends the use of its drug Amvuttra to the treatment of a prevalent cardiomyopathy. This is the second FDA approval for this indication in four months and the third overall approval, introducing new competition to the treatment of diseases that lead to heart failure and frequent hospitalizations, often becoming fatal within five years of diagnosis.

AMVUTTRA is now approved for the treatment of adults who develop cardiomyopathy from thioprotein amyloidosis (ATTR), a disease in which abnormal versions of liver proteins through trypsin (TTR) lead to the accumulation of amyloid in tissues in the body. The regulatory decision announced late Thursday covers natural development of Attrymomypathy, as well as hereditary diseases. Amvuttra is the third drug approved for ATT-type cardiomyopathy, second only to Pfizer’s product, which has become the standard of care approved last fall and Bridgebio Pharma drug. But Amvuttra introduced a new mechanism of action to the disease.

Based in Cambridge, Massachusetts, Alnylam specializes in RNA interference drugs, and therapies provide small pieces of RNA to “silence” a gene, thus defeating the production of the protein that causes the disease. AMVUTTRA is designed to reduce the levels of TTR proteins driving attr. The drug was first approved in 2022 as an injection every three months and is a treatment for polyneuropathy caused by the disease.

FDA approved AMVUTTRA in ATT myopathy, based on data from the placebo-controlled phase 3 study Helios-B, with the main goal of measuring death from all causes and recurrent cardiovascular events. Results from this comprehensive endpoint showed that AMVUTTRA was statistically significant decrease by 28% during the treatment period up to 36 months. On the secondary target of measuring mortality, the results showed 36% of the 42-month period. The results were published in the New England Journal of Medicine last August.

“We believe that Amvuttra has the potential to become a new standard of care for cardiomyopathy for ATT,” Alnylam CEO Yvonne Greenstreet said on Thursday night’s conference call. “Our confidence stems from the success of the Helios-B study, which demonstrates that the therapeutic characteristics of AMVUTTRA support the front-line potential.”

The Pfizer received its first FDA approval for ATT myopathy in 2019. Its drug Tafamidis is sold as Vyndaqel (four times the capsule per day) and Vyndamax (used as the daily capsule), which binds to Mutant Ttr Protein to prevent proteins from building protein characteristics. Although the Pfizer small molecule is approved in other countries for the treatment of aphrodisiacs, its U.S. approval only covers cardiomyopathy caused by the disease. Pfizer reported that in 2024, the Vyndaqel family's global sales were $5.5 billion, a 65% increase over the previous year. Most of the revenue from the product comes from the United States

Last November, the FDA approved Bridgebio Drug Attruby to bring a new cardiomyopathy competition. Last month, it was approved by European regulators twice a day. Like Pfizer, atteruby is a TTR stabilizer. But Bridgebio believes its drug is a better stabilizer, and the product label language shows that the pill achieves “almost complete stability” of the target protein.

Recognizing the warnings of cross-trial comparisons, some differences may affect how prescribers and patients view these therapies. Leerink Partners analyst Mani Foroohar wrote in a note sent to investors on Friday that the reduction in cardiovascular hospitalizations and emergency heart failure and the emergency heart failure visit with Amvuttra were much lower than what Attruby showed. But William Blair's Myles Minter highlighted data on all-cause mortality from Alnylam drugs, which is an advantage for Atteruby, which in its key study did not reach statistical significance in this measure. Pfizer's tafamidis tag includes mortality benefits.

“give [all-cause mortality] “The data and totals in the Amvuttra tag are derived from the patient population, some of whom are receiving Tafamidis treatment, and we believe Amvuttra is the best choice for patients and healthcare providers,” Minter said.

Minter added that subgroup analysis showed that AMVUTTRA was used in the patient population, including younger, healthier patients reflecting the current disease population. William Blair believes that in these patients, Alnylam drugs are suitable for frontline use.

Amvuttra's headwind is its price. For Attryman's Alnylam, the wholesale price of Amvuttra will be the same wholesale price as Attry Polyneuropathy, with an injection of about $119,000 per year or $476,000 per year. In a speech by investors, the net price of the product will drop over time as the drug is absorbed. But currently, Pfizer’s ATT-type cardiomyopathy drug is cheaper, with the annual price of $267,987 while Bridgebio’s attruby is priced at $244,500 per year.

With significantly higher price tags, Leerink analysts expect the challenge will allow payers to cover Amvuttra in new instructions. But William Blair analysts believe that Amvuttra’s label is enough to ensure wide range of payers. The company also sees quarterly injections as an advantage because this dosing regimen improves compliance compared to the need to remember to take pills every day.

The approval obtained by Amvuttra in cardiomyopathy provides an estimated 300,000 patients worldwide compared to the larger market for polyneuropathy. Furthermore, most of these patients are undiagnosed, providing companies with opportunities to reach new patients.

In 2024, Alnylam reported that Amvuttra's revenue in polyneuropathy indications was $970.5 million. With new approvals, the company expects revenue from TTR products this year to $1.6 billion to $1.72 billion. Although Amvuttra can already be used for multiple myopathies, Alnylam is predicting the second half of the drug's launch in 2025 as the company continues to discuss value-based agreements with payers about Amvuttra and ensures formulas for the drug in its new instructions.

In other countries, Amvuttra is still under review. Alnylam expects Japan to make regulatory decisions in the second quarter of this year. Other decisions are expected to be made in Europe, Brazil and Canada later this year. In the recent semester, Alnylam will provide additional AMVUTTRA data at the American Cardiology Conference in Chicago in late March.

Photos of Alnylam Pharmaceuticals