Amvuttra effective in East Asian patients with hATTR-PN: Trial data
Treatment shown to ease symptoms, reduce disability, improve quality of life
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Amvuttra (vutrisiran) safely and effectively eases symptoms, reduces disability, and improves quality of life in East Asian adults with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), according to a subgroup analysis of the global Phase 3 HELIOS-A clinical trial (NCT03759379). Top-line data from the trial supported the therapy’s approval for hATTR-PN.
“Although the number of East Asian patients in HELIOS-A was small, this post hoc analysis showed similar outcomes to those in the overall study populations, indicating that [Amvuttra] is effective and well tolerated” in a patient population “that has historically been underrepresented in [hATTR-PN] clinical trials,” researchers wrote.
Post hoc analyses are those specified and conducted after a trial has been completed and data have been collected.
The findings were described in the study “Efficacy and Safety of Vutrisiran in Patients with Hereditary Transthyretin-mediated Amyloidosis with Polyneuropathy: Analysis of the East Asian Subpopulation from HELIOS-A,” which was published in Neurology and Therapy.
Amvuttra reduces production of key protein
Also known as familial amyloid polyneuropathy, hATTR-PN is caused by mutations in the TTR gene. It is marked by the buildup of misfolded transthyretin (TTR) protein into toxic clumps, called amyloid deposits, in the peripheral nerves, or those outside the brain and spinal cord. This causes damage to the nerves, or polyneuropathy, and neurological symptoms.
Amvuttra, marketed by Alnylam Pharmaceuticals, is an approved treatment for hATTR-PN that’s designed to reduce TTR production in the liver, where the protein is mostly produced. The medication is expected to ease symptoms and slow or prevent the progression of hATTR-PN.
Regulatory approvals of Amvuttra, including in Asia, were based on data from the HELIOS-A study, in which 122 adult hATTR-PN patients received an under-the-skin injection of Amvuttra every three months for 18 months, or about 1.5 years.
Participant outcomes were compared with those of 77 hATTR-PN patients who received a placebo in the Phase 3 APOLLO trial (NCT01960348), a study that supported the approval of Alnylam’s first-generation hATTR-PN therapy, Onpattro (patisiran).
Data showed that Amvuttra-treated patients had reduced neurological symptoms and disability compared with the external placebo group.
Patients from Asia underrepresented in ATTR registries
In this study, a team of researchers analyzed the safety and efficacy of the therapy in a subgroup of East Asian patients with hATTR-PN from the HELIOS-A study.
“Patients from Asia are underrepresented in transthyretin amyloidosis (ATTR) registries, and face challenges regarding early diagnosis and treatment access,” the researchers wrote. ATTR is a group of conditions, including hATTR-PN, that are marked by the buildup of toxic TTR clumps.
The team compared data from the 12 HELIOS-A participants enrolled at East Asian sites (Japan, South Korea, and Taiwan) with that of the 21 East Asian patients who received a placebo in the APOLLO trial.
Participants who received Amvuttra had a median age of 57 years, while those in the external placebo group had a median age of 62 years.
In both groups, about three-quarters of patients were men, and two-thirds had non-V30M variants in the TTR gene, most commonly the A97S mutation (47.6%). V30M, or Val30Met, is the most common hATTR-PN-causing mutation in certain countries, including Japan, whereas the A97S mutation is common in Taiwan.
In HELIOS-A, the East Asian subgroup had a higher mean modified Neuropathy Impairment Score +7, indicating more severe polyneuropathy-related symptoms, than the overall trial population.
The consistency of treatment effects, including clinical response, TTR reduction, and safety profile, supports the suitability of [Amvuttra] in East Asian patients with [hATTR-PN].
Among East Asian patients, those treated with Amvuttra experienced significantly greater reductions in the mNIS+7 — 20.18 points after nine months and 30.75 points after 18 months — compared with those in the external placebo group. In the overall HELIOS-A population, the reductions in these scores were 17 and 28.55 points, respectively.
In addition to this main outcome measure, East Asian participants treated with Amvuttra also showed greater improvements in measures of quality of life, walking speed, and nutritional status relative to those given the placebo. Amvuttra was also associated with greater reductions in disability. These changes “were also similar to the overall population at month 18,” the team wrote.
Within three weeks of the first Amvuttra dose, East Asian patients experienced a “rapid and robust reduction” in blood TTR levels, which was maintained for 18 months. These effects were also consistent with those seen in the overall study population.
The most frequently reported adverse events in the East Asian patients treated with Amvuttra included fall, diarrhea, swelling of the extremities, and dizziness (8.3% each). Fewer patients on the therapy experienced adverse events, serious adverse events, and/or death relative to those in the placebo group.
“The consistency of treatment effects, including clinical response, TTR reduction, and safety profile, supports the suitability of [Amvuttra] in East Asian patients with [hATTR-PN],” the researchers wrote.
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