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 ATTR-CM Landscape Just Got a New Challenger
Cardiac amyloidosis, particularly transthyretin amyloid cardiomyopathy (ATTR-CM), isn’t just a medical challenge—it’s a battleground. Until recently, the space was dominated by Pfizer and BridgeBio. But now, Alnylam Pharmaceuticals has entered the ring with the recent FDA approval of Amvuttra (vutrisiran). This move isn’t just a company milestone—it’s a direct shot at reshaping the landscape of heart disease treatments.
Let’s dive into how this approval changes everything.
What Is ATTR-CM and Why It Matters
Understanding the Disease
ATTR-CM is a rare, progressive, and potentially fatal heart condition caused by deposits of misfolded transthyretin (TTR) protein in the heart. These deposits stiffen the heart muscle, leading to heart failure, arrhythmias, and decreased quality of life.
The Unmet Need
While there have been advancements, ATTR-CM remains underdiagnosed and undertreated. The clock is ticking for patients, and any delay in therapy can be fatal. This is why new treatment options like Amvuttra are generating serious buzz.
Meet the New Player: Amvuttra by Alnylam
What Is Amvuttra?
Amvuttra (vutrisiran) is a next-generation RNA interference (RNAi) therapeutic. It targets the root cause of the disease: the overproduction of TTR protein in the liver.
How It Works
Think of RNAi as a molecular “mute button.” Amvuttra silences the TTR gene, stopping excess protein from being made in the first place. That’s next-level science in action.
FDA Approval—A Game-Changer
In 2022, Amvuttra was approved for hereditary ATTR polyneuropathy. But in 2025, the FDA extended its approval for ATTR-CM, signaling a major victory for Alnylam.
Market Implications
This opens up a market projected to reach over $6 billion by 2030. With this approval, Alnylam isn’t just participating—it’s competing for dominance.
The Existing Titans—Pfizer and BridgeBio
Pfizer’s Tafamidis
Pfizer’s Vyndamax (tafamidis) is the current market leader. It works by stabilizing the TTR protein, preventing it from breaking apart and forming harmful deposits.
BridgeBio’s Acoramidis
BridgeBio’s acoramidis is a late-stage contender. It also stabilizes TTR and has shown promising results in Phase 3 trials.
Alnylam’s Competitive Edge
A Different Mechanism
Unlike its rivals, Amvuttra doesn’t stabilize TTR—it prevents its production altogether. That could mean better outcomes, especially for patients not responding to stabilizers.
Less Frequent Dosing
Amvuttra is given once every 3 months, compared to daily pills from Pfizer or BridgeBio. That’s a huge win for patient convenience.
Global Expansion Plans
Alnylam isn’t just thinking local—it’s thinking global. With approvals pending in Europe and Asia, it’s clear the company wants worldwide market penetration.
Market Forecast—Three’s Not a Crowd
Analysts predict the ATTR-CM market will become a three-way race, with:
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Pfizer retaining early dominance
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BridgeBio capturing niche subgroups
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Alnylam disrupting the status quo
Strategic Partnerships Ahead?
Will Big Pharma step in? Licensing deals, collaborations, or even acquisitions are all on the table. The stakes are high, and the clock is ticking.
Impact on Patients
More Options, Better Outcomes
For patients, this is nothing short of a revolution. With three distinct mechanisms, doctors can personalize treatment plans like never before.
Precision Medicine Takes the Stage
As biomarkers and genetic testing become more common, these therapies can be matched to individual patient profiles, maximizing efficacy.
Pricing and Access—The Elephant in the Room
Will Amvuttra be affordable? At launch, it was one of the most expensive drugs for polyneuropathy. Pricing for ATTR-CM hasn’t been confirmed yet—but it’s a key factor in adoption.
What’s Next for Alnylam?
Pipeline Watch
Alnylam isn’t stopping here. It has a robust RNAi pipeline targeting everything from hypertension to Alzheimer’s.
Real-World Data Will Be Crucial
Post-market studies will tell us if Amvuttra can truly deliver on its promise in the real world.
Industry Buzz & Physician Sentiment
Doctors are cautiously optimistic. The novel mechanism, coupled with quarterly dosing, is seen as a major leap forward. But long-term outcomes and cost will determine real adoption.
A Paradigm Shift in ATTR-CM Treatment
With Alnylam’s entry, the paradigm shifts from stabilizing to silencing the disease at its genetic source. This represents a whole new era—not just for ATTR-CM, but for precision cardiology as a whole.
Final Thoughts—The Fight Is Just Beginning
Three’s company, but it’s also a showdown. Alnylam’s Amvuttra approval means patients, physicians, and the entire healthcare system now have more tools—and tougher choices. As these three pharma giants battle it out, one thing’s for sure: the real winners are the patients.
