Vutrisiran Now Under Review for Approval in Europe for FAP Treatment

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by Marta Figueiredo PhD |

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The European Medicines Agency (EMA) has agreed to review Alnylam Pharmaceuticals’ application requesting the approval of vutrisiran, its second-generation RNA interference (RNAi) therapy candidate for familial amyloid polyneuropathy (FAP).

Hereditary ATTR (hATTR) amyloidosis, which includes FAP, “is a rare, rapidly progressive, debilitating and fatal condition and we are delighted that the EMA has agreed to review the regulatory submission for vutrisiran based on the positive 9-month data from the HELIOS-A Phase 3 study,” Rena Denoncourt, vice president and TTR Franchise lead at Alnylam, said in a press release.

This is a change to a previous announcement that stated the therapy would only be submitted to the EMA for approval after 18-month results were made available from the ongoing HELIOS-A study (NCT03759379), expected later this year. Instead, these data will be provided to the agency during its application review.

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“If approved, we believe that vutrisiran will provide an important new subcutaneously [under-the-skin] administered, once-quarterly treatment option for patients, with the potential to reverse manifestations of the disease in [FAP patients],” Denoncourt said.

“We look forward to working closely with the EMA to bring vutrisiran to the hATTR amyloidosis community in Europe,” Denoncourt added.

Should the European Commission approve vutrisiran, health authorities in each European Union member state will decide whether to add the therapy to their respective public health programs, in which patients can access the treatment at low or no cost.

A similar application is currently being reviewed in the U.S., where a decision is expected no later than April 14, 2022. Regulatory filings to health authorities in Brazil and Japan are also planned for later this year.

Vutrisiran is Alnylam’s successor to Onpattro (patisiran) — also approved for FAP and administered directly into the bloodstream once every three weeks — and allows for a four-times-a-year, or potentially a biannual, dosing schedule.

While both therapies use a process called RNAi to lower the production of transthyretin (TTR), the faulty protein that causes FAP, vutrisiran is designed to have greater stability, potentially allowing for a stronger and long-lasting effect than Onpattro.

As such, Alnylam’s next-generation, long-acting, subcutaneous RNAi therapy has the potential to require less-frequent dosing and lower the burden and overall healthcare costs for patients, while improving their quality of life.

Vutrisiran received orphan drug designation in both the U.S. and Europe, as well as fast-track designation in the U.S., for the treatment of FAP and related hATTR diseases. These designations are meant to accelerate its development and regulatory review.

The ongoing HELIOS-A study, expected to conclude in May 2024, is evaluating the safety and efficacy of 1.5 years of treatment with vutrisiran against Onpattro in 164 adults with FAP, recruited at 57 sites across 22 countries. Vutrisiran (25 mg) was given through a subcutaneous injection once every three months.

Notably, the group of patients given a placebo in the Phase 3 APOLLO trial (NCT01960348), whose data supported Onpattro’s approval, were used as an external control group for most study goals.

HELIOS-A’s top-line, nine-month data showed that the trial met both its main and secondary goals, with vutrisiran-treated patients experiencing less severe neurologic impairments and significant improvements in quality of life and walking speed, compared with the APOLLO placebo group.

A rapid and sustained reduction in blood TTR levels, which dropped by 83% from the study’s start, was also observed in vutrisiran-treated patients. Similar trends were seen among patients given Onpattro.

Vutrisiran also was associated with improvements in other key exploratory goals, including in different measures of heart health, nutritional status, and overall disability.

The second-generation therapy was generally safe and well tolerated. The rates of the most common adverse events, including diarrhea, pain in the extremities, falls, and urinary tract infections, in vutrisiran-treated patients were similar or lower than those reported for the historical placebo group.

After completing the 18-month treatment period, participants may choose to enter the study’s extension phase, in which all will receive either 25 mg of vutrisiran once quarterly, or 50 mg of vutrisiran once every six months for 1.5 years.