Amvuttra gets EU approval to treat adults with ATTR-CM

European Commission expands indication for treatment

Michela Luciano, PhD avatar

by Michela Luciano, PhD |

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The European Commission has expanded the indication of Amvuttra (vutrisiran) to include adults with ATTR amyloidosis with cardiomyopathy, or heart damage (ATTR-CM), regardless of whether they carry disease-causing mutations.

“Estimates show approximately 100,000 people are affected by ATTR amyloidosis across Europe, most with cardiomyopathy, so this approval marks a critical step toward addressing this underserved patient population,” Pushkal Garg, MD, chief medical officer at Alnylam Pharmaceuticals, said in a company press release. “We now look forward to securing access to AMVUTTRA for eligible patients across the EU as quickly as possible.”

Alnylam’s Amvuttra is approved in the European Union (EU) for adults with familial amyloid polyneuropathy (FAP) — also known as hereditary ATTR amyloidosis with polyneuropathy — a related condition that, instead of the heart, mainly affects the nerves outside the brain and spinal cord.

“AMVUTTRA is supported by a well-established efficacy and safety profile, with over 6,000 patient-years of global experience in the treatment of [FAP],” Garg said.

As an RNA interference (RNAi) therapy, Amvuttra is designed to lower the production of transthyretin (TTR), the protein that’s faulty in FAP and ATTR-CM, by targeting and silencing its messenger RNA, a molecule used as a template to make proteins.

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Approvals in U.S., Brazil

With the new indication, Amvuttra becomes the first RNAi therapy approved in the EU for both FAP and ATTR-CM.

The EU approval comes a few months after Amvuttra was cleared in the U.S. to treat adults with ATTR-CM, making it the first U.S.-approved treatment for both FAP and ATTR-CM. The therapy is approved for the same indication in Brazil.

The European Medicines Agency (EMA) in May issued a positive opinion to keep Amvuttra’s orphan drug designation in the EU for ATTR amyloidosis. The maintenance of that designation will grant Alnylam 10 years of market exclusivity after the therapy’s approval.

ATTR amyloidosis is a group of conditions marked by the misfolding of the TTR protein, which is coded by the TTR gene. When TTR misfolds, it forms toxic protein clumps, or amyloid deposits, that build up in various tissues and organs, leading to progressive damage.

FAP, an hereditary form of the disease, primarily affects the nerves outside the brain and spinal cord, resulting in neurological symptoms such as numbness, pain, and muscle weakness. In some cases, the heart is also affected, leading to cardiomyopathy.

In ATTR-CM, which can be inherited or noninherited, the misfolded TTR protein builds up mainly in the heart muscle. If left untreated, it can impair heart function, reduce exercise capacity, and eventually lead to heart failure.

By reducing the amount of TTR protein, Amvuttra helps to prevent the buildup of amyloid deposits in tissues, slowing disease progression and easing symptoms. The therapy is administered through an under-the-skin injection, once every three months, in a hospital or clinic.

Amvuttra’s approvals for ATTR-CM were based on positive results from a Phase 3 clinical trial, called HELIOS-B (NCT04153149), which enrolled 655 adults with hereditary or nonhereditary ATTR-CM. Participants were randomly assigned to receive either Amvuttra or a placebo every three months for up to three years.

The study included patients who were already receiving other standard-of-care treatments. These included tafamidis, an approved therapy for ATTR-CM that is sold as Vyndamax in the U.S. and Vyndaqel in Europe, where it is also approved for early-stage FAP.

By the end of the study period, participants treated with Amvuttra showed a 28% reduction in the risk of death from any cause and recurrent cardiovascular events compared with those on the placebo. Among those receiving Amvuttra alone, the risk was reduced by 33%.

Longer-term follow-up data showed that the risk of death dropped by 35% with Amvuttra in the overall population and by 34% in the group receiving Amvuttra alone. Treated patients also showed less of a decline in physical function and quality of life.

Rates of adverse events were similar between the Amvuttra and placebo groups. The most common adverse reactions to the therapy included injection site reactions and mild increases in certain liver enzymes.

The findings “provide compelling evidence to support the use of AMVUTTRA as a first-line treatment option for patients with ATTR-CM,” said Marianna Fontana, MD, PhD, a HELIOS-B investigator and a professor of cardiology at University College London’s National Amyloidosis Centre.

“The trial enrolled a broad population reflective of real-world clinical practice, and that’s what makes the results so meaningful,” Fontana said. “This is a milestone for patients, who now have a new treatment option that has the potential to significantly improve outcomes of this disease.”