Despite growing competition in the transthyretin amyloid cardiomyopathy (ATTR-CM) field, Alnylam is hoping its RNA interference approach can set it apart from its peers. And now, the Massachusetts-based drugmaker has a fresh FDA approval to support its thesis.

The FDA has signed off on Alnylam’s Amvuttra, also known as vutrisiran, as a treatment for cardiomyopathy of wild-type or hereditary ATTR-CM in adults to reduce the chance of cardiovascular death, hospitalizations and urgent heart failure visits.

Thanks to a previous nod in 2022, Amvuttra is now the first medication approved in the U.S. to treat both ATTR-CM and polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN), Alnylam noted in a Thursday release.

Amvuttra now enters a potentially lucrative field largely dominated by Pfizer, whose Vyndaqel (tafamidis) family of transthyretin (TTR) stabilizer drugs won their initial ATTR-CM nods from the FDA in 2019. Meanwhile, BridgeBio’s TTR stabilizer Attruby crossed the FDA finish line in November and its launch is progressing smoothly so far.

Speaking to those that came before, Alnylam’s chief commercial officer Tolga Tanguler credited Pfizer’s tafamidis franchise for establishing the ATTR-CM category and boosting diagnosis rates. Still, more work remains to be done, and Alnylam figures Amvuttra, with its unique gene silencing approach, could be a game-changer for the field, the CCO said in a recent interview with Fierce Pharma.

“I think what Pfizer has done in terms of education and increasing diagnosis—in terms of developing the infrastructure and ecosystem—has been phenomenal,” Tanguler said.

Still, given that the only drugs available for the disease up until now have been TTR stabilizers, Tanguler figures the approval of a new mechanism of action will expand “this severe, but significantly underdiagnosed disease.”

Amvuttra is an RNA interference drug that works to deliver a rapid knockdown of TTR, which helps attack ATTR-CM at its source, Alnylam said in its approval announcement. By quickly knocking down TTR production, Amvuttra decreases deposition of TTR fibrils, which form amyloid that cause permanent cardiovascular damage and premature death in patients with ATTR-CM.

The FDA based its approval decision on data from Alnylam’s phase 3 Helios-B study, which the company’s medical chief, Pushkal Garg, M.D., previously described as a “grand slam.”

In the study, which met all 10 of its primary and secondary endpoints, Amvuttra reduced the risk of all-cause mortality (ACM) and recurrent cardiovascular (CV) events in the overall patient population by 28% versus placebo during a double-blind treatment period of up to 36 months. That same Amvuttra study population experienced a 36% mortality reduction through 42 months during an open-label extension portion of the trial.

Alnylam has estimated there are around 9,000 U.S. ATTR-CM patients in the first-line treatment setting, plus another 10,000 or so second-line patients who could switch over from tafimidis, analysts at Jefferies wrote in a note to clients this week. That potential patient pool could expand dramatically if diagnosis rates were to improve.

Jefferies predicts Amvuttra can bring home $250 million in cardiomyopathy sales this year, with $200 million of that sum coming from sales generated by tafimidis converts.

Meanwhile, Tanguler disagreed with the notion that drugs like tafimidis or BridgeBio’s recently approved cardiomyopathy med Attruby are more convenient simply because they’re taken orally. While those drugs must still be taken daily, Amvuttra is delivered via four subcutaneous injections throughout the year, which Tanguler argued is similar in terms of convenience and could improve adherence to the therapy in a swiftly progressing and ultimately fatal disease.

With a prior approval in hATTR-PN, Amvuttra isn’t launching into the cardiomyopathy space blind.

“This is not a standing start for us,” Tanguler said. “It’s a running start.”

ATTR, whether the cardiomyopathy or polyneuropathy manifestation, is primarily diagnosed and treated at cardiology centers in the U.S., where Alnylam already has a strong presence thanks to Amvuttra’s initial FDA green light in polyneuropathy, Tanguler explained.

Given that polyneuropathy was a narrower indication than cardiomyopathy, Alnylam has had to scale up its outreach efforts in light of its Amvuttra expansion goals, the CCO said.

Previously, Alnylam had been contacting roughly one-third to 40% of those cardiology centers, Tanguler said. Now, the company wants to cast a wide net by reaching 100%.

From another angle, there are around 3,700 doctors treating 90% of ATTR-CM patients and around 170 healthcare systems that account for roughly 80% of all ATTR-CM prescriptions in the U.S., the Jefferies team said this week. Alnylam plans to work with all of these high-volume prescribers and health systems during its launch, the research team said.

“We are fully scaled to be able to do that, and even more,” Tanguler said of the goal.

As far as pricing goes, Amvuttra in cardiomyopathy will cost roughly $450,000 per year before discounts, Citi analysts wrote in a note late Thursday. While that price tag is on par with the drug’s cost in polyneuropathy, it comes in well above those for Pfizer’s Vyndaqel offerings and BrideBio’s Attruby in ATTR-CM, the Citi team noted.

Alnylam has communicated that with rebates and other discounts, Amvuttra’s net price could ultimately drop over time as revenue starts building in the cardiomyopathy indication, the analysts said.

Additionally, the company noted in its approval release that Amvuttra in hATTR-PN is covered by insurers for around 99% of patients, most of whom pay $0 out of pocket for the drug. Alnylam said it expects to achieve similarly broad coverage and out-of-pocket costs in the cardiomyopathy indication, too. 

With the new approval, Alnylam has an opportunity to make a big mark on the sales front. For an idea of the potential opportunity at stake, Pfizer reported (PDF) Vyndaqel sales at above $5.4 billion last year, a 64% increase from the prior year.

While Alnylam’s commercial chief didn’t go into specifics about his company’s sales expectations for Amvuttra, he was clear that he expects the cardiomyopathy approval to be significant for the biotech.

“I think this is going to be a growth story,” Tanguler said. “And [it's] a category growth story, rather than just us or them.” 

Editor's note: This story has been updated with information on Amvuttra's pricing in ATTR-CM.