The FDA on Thursday approved Alnylam’s RNAi therapeutic a few days ahead of schedule, giving Amvuttra (vutrisiran) a green light to treat transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The therapy’s potential to change the ATTR-CM treatment landscape earned it a place on FirstWord’s list of drugs that will shape 2025. Amvuttra is now the second drug — and first with a wholly unique mechanism of action — to challenge Pfizer’s Vyndaqel/Vyndamax (tafamidis), which had been the sole ATTR-CM treatment option for about five years until the November 2024 approval of BridgeBio’s Attruby (acoramidis). To make up for BridgeBio’s headstart, Alnylam had cashed in a priority review voucher to ensure a speedy review of Amvuttra. Like Vyndaqel, Attruby is an oral TTR stabiliser, whereas Amvuttra is an RNAi therapeutic that delivers rapid knockdown of TTR. It was first approved for polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in 2022.
Initially greenlit in 2019, the Vyndaqel family has proved to be particularly lucrative for Pfizer. The products brought in a total of $5.5 billion in global sales last year, up 60% from 2023 revenues of $3.3 billion. Alynylam is hoping to capitalise on that fast-growing ATTR-CM market, as Amvuttra already sits on the cusp of blockbuster status. The RNAi therapeutic brought in $970 million in sales last year from its hATTR-PN indication; following its label expansion Thursday, the pharma projected full-year 2025 revenue between $1.6 billion and $1.7 billion for its TTR portfolio, which also includes Onpattro (patisiran). Given as four subcutaneous doses per year, Amvuttra’s current hATTR-PN wholesale acquisition cost of $119,000 per prefilled syringe will remain the same for ATTR-CM.
Newcomer showdown Amvuttra will now go head-to-head with Attruby to wrestle away a piece of Pfizer’s ATTR-CM pie. A series of physician polls conducted by FirstWord last year showed that cardiologists view Amvuttra as an important new treatment option, but whether it, or Attruby, offers the biggest benefit to patients depends on different interpretations of available clinical data. For related analysis, see Physician Views Results: Cardiologists have much to ponder with ATTR-CM treatment options set to expand; Physician Views Poll Results: Amvuttra another compelling treatment option for ATTR-CM, say majority of cardiologists; and Physician Views Results: Cardiologist feedback suggests Alnylam well placed to take on Pfizer in ATTR-CM field. Thursday’s approval was based on the results of the Phase III HELIOS-B trial, in which Amvuttra achieved statistical significance compared to placebo on all 10 pre-specified primary and secondary endpoints.
Specifically, the RNAi therapeutic reduced the composite endpoint of all-cause mortality (ACM) and recurrent cardiovascular (CV) events by 28% compared to placebo after 36 months. In addition, Amvuttra reduced ACM by 36% in the overall population at up to 42 months and by 35% in those not on tafamidis at baseline. Attruby earned its clearance on the back of data from the ATTRibute-CM Phase III trial, in which the drug saw a 25% reduction in ACM and a 50% decrease in CV-related hospitalisations at 30 months.
The New Contender in ATTR-CM Treatment
If you’re tracking the race for innovative therapies in transthyretin amyloid cardiomyopathy (ATTR-CM), you know the battleground just got more intense. With the recent approval of Amvuttra by Alnylam Pharmaceuticals, a powerful new player enters the ring alongside Pfizer and BridgeBio Pharma. This move isn’t just a business expansion — it’s a game changer for patients and the industry alike.
What Is ATTR-CM and Why Does It Matter?
Understanding the Silent Heart Threat
ATTR-CM is a rare but deadly condition where abnormal amyloid proteins accumulate in the heart, causing serious cardiac dysfunction. Without timely intervention, it leads to heart failure and drastically lowers life quality.
Limited Treatment Options Until Recently
For years, patients and doctors faced frustratingly few options. But with breakthrough therapies from companies like Pfizer, BridgeBio, and now Alnylam, hope is on the horizon.
Alnylam’s Amvuttra — The New Hope
How Amvuttra Works
Amvuttra (vutrisiran) is a small interfering RNA (siRNA) therapy designed to silence the production of the faulty transthyretin protein responsible for amyloid buildup.
What Sets Amvuttra Apart
Unlike previous therapies, Amvuttra offers the convenience of subcutaneous dosing every three months, promising less frequent administration without compromising effectiveness.
Pfizer and BridgeBio — The Established Fighters
Pfizer’s Vyndaqel and Vyndamax
Pfizer’s Vyndaqel (tafamidis) and Vyndamax have been mainstays in the ATTR-CM treatment arena. These drugs stabilize the transthyretin protein to prevent it from forming harmful amyloids.
BridgeBio’s Acoramidis
BridgeBio’s acoramidis is a novel transthyretin stabilizer currently in late-stage development, promising to add more muscle to the treatment arsenal.
What Amvuttra’s Approval Means for the Market
Increased Competition Spurs Innovation
The entry of Amvuttra is set to intensify competition, driving all players to improve efficacy, safety, and patient experience.
Pricing and Access Dynamics
With three major contenders, there could be downward pressure on pricing and expanded access, which is great news for patients.
Patient-Centric Benefits of Amvuttra
Convenience Is King
Who wants to visit the clinic monthly? Amvuttra’s quarterly dosing is a breath of fresh air, simplifying treatment adherence.
Fewer Side Effects?
Early data suggest Amvuttra’s safety profile is favorable, reducing the risk of adverse reactions common with some treatments.
The Science Behind siRNA Therapies
Precision Medicine in Action
Amvuttra’s mechanism showcases the power of gene silencing technology, targeting the disease’s root cause rather than just managing symptoms.
A Growing Trend in Rare Disease Therapies
siRNA therapies are increasingly popular, opening new avenues for diseases once deemed untreatable.
How Will Pfizer and BridgeBio Respond?
Possible Pipeline Acceleration
Both companies might fast-track their R&D efforts or pursue combination therapies to stay competitive.
Strategic Partnerships and Mergers
Industry watchers predict potential alliances or licensing deals to consolidate market share and enhance treatment portfolios.
Challenges Ahead for Alnylam and Amvuttra
Market Penetration Hurdles
Despite approval, convincing physicians and payers to switch or adopt new treatments can be tough.
Long-Term Efficacy and Safety
While promising, Amvuttra still needs to prove its benefits over years of real-world use.
Patient Advocacy and Awareness
Educating on ATTR-CM
More awareness campaigns are necessary to ensure patients get diagnosed early and access these cutting-edge treatments.
H3: Role of Patient Support Programs
Alnylam and others invest in support programs to assist patients with treatment navigation, boosting adherence and outcomes.
Global Impact and Access
Expanding Reach Beyond the U.S.
Approval in multiple countries is crucial for broad patient access worldwide.
Addressing Healthcare Disparities
Manufacturers and healthcare systems must work together to reduce inequalities in rare disease treatment availability.
What’s Next in the ATTR-CM Arena?
Next-Generation Therapies in Development
Gene editing, CRISPR, and novel stabilizers are on the horizon, promising even more effective solutions.
Personalized Medicine Approaches
Tailoring treatment to patient genetics and disease progression could revolutionize outcomes.
Why This Competition Matters to You
More Choices, Better Care
When companies compete fiercely, patients benefit from improved drugs and affordable pricing.
The Promise of Longer, Healthier Lives
These advances aren’t just scientific victories; they’re real chances for patients to live fuller lives.
Conclusion: A Triumphant Trio in the Fight Against ATTR-CM
The approval of Amvuttra catapults Alnylam into the heavyweights’ ring alongside Pfizer and BridgeBio, creating a dynamic, innovative battlefield in ATTR-CM treatment. For patients, it means more hope, better options, and a brighter future. As these three companies push boundaries, we can expect rapid advancements and exciting developments in the fight against this devastating disease.
