Amvuttra improves multiple life quality measures: Trial data
Physical function also benefited from the therapy in HELIOS-A clinical trial
Amvuttra (vutrisiran) provided significant clinical benefits in multiple measures of quality of life and physical function in people with familial amyloid polyneuropathy (FAP), according to published details of the HELIOS-A clinical trial.
Benefits, which also included early gains in nutritional status, were most pronounced in those in the early stages of the disease, data showed.
“The findings of this study support the clinical benefit of [Amvuttra] as an effective treatment that can improve the lives of patients with [FAP] and emphasize the importance of early and effective treatment,” researchers wrote.
The study, “Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy,” was published in the journal Neurology and Therapy.
Transthyretin is a protein that transports vitamin A and the hormone thyroxine throughout the body. Inherited mutations in the TTR gene that encodes for transthyretin result in a faulty protein that forms toxic clumps, called amyloid, in tissues and organs.
In FAP, also called hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy, amyloid build-up in peripheral nerves, or those found outside the brain and spinal cord, causes damage, leading to symptoms of neuropathy.
Amvuttra lowers production of faulty transthyretin protein
Alnylam Pharmaceuticals‘ Amvuttra, an approved treatment for adults with FAP, works by lowering the production of the faulty transthyretin protein with the goal of reducing amyloid build-up and lessening symptoms.
Its approval was based on data from the Alnylam-sponsored Phase 3 HELIOS-A clinical trial (NCT03759379), in which a total of 122 adult FAP patients received an under-the-skin injection of Amvuttra every three months for 18 months.
Participant outcomes were compared with 77 FAP patients who received a placebo in the Phase 3 APOLLO trial (NCT01960348), a study that supported the approval of Alnylam’s first-generation FAP therapy Onpattro (patisiran).
Previously reported data showed Amvuttra eased neuropathy symptoms and disability after nine months of treatment compared with the external placebo group, meeting the trial’s primary goal. Treatment also improved walking speed, nutritional status, quality of life, and heart health over 18 months, meeting several secondary objectives.
The newly published peer-reviewed report confirmed previous data and provided further details of Amvuttra’s impact on quality of life, physical function, and nutritional status over 18 months.
Before treatment (baseline), quality of life was markedly impaired in both Amvuttra and external placebo groups, as assessed with the Norfolk Quality of Life‐Diabetic Neuropathy (QOL‐DN) questionnaire. This patient-reported tool is an indicator of neuropathic symptoms and their impact on daily life activities.
Patients with worse quality of life at baseline had more severe disease, as reflected by a higher polyneuropathy disability (PND) stage, a classification of FAP progression focusing on walking abilities.
Improvements seen in quality of life
With Amvuttra, there was an improvement in quality of life, as indicated by a 1.2-point mean decrease in Norfolk QoL-DN scores after 18 months, while the placebo group experienced a worsening in quality of life, as showed by a 19.8-point mean increase.
While increases in quality of life were seen across all PND stage levels, those with a lower PND stage at baseline, or less severe disease, experienced the greatest treatment benefit over 18 months.
Amvuttra was favored over a placebo in several symptom-related domains of the Norfolk QOL-DN, which included numbness, pins and needles, superficial pain, deep pain, and weakness.
A significant benefit in patients’ self-rated global health also was observed in Amvuttra-treated patients, as measured by the EuroQoL visual analog scale (EQ-VAS), with scores ranging from 0 (worst possible health) to 100 (best possible health). Mean scores in the Amvuttra group increased by 2.1 points versus a decrease of 11.6 points with a placebo.
Physical function was assessed by participants’ walking speed over 10 meters (33 feet). After 18 months, Amvuttra-treated patients walked 0.24 meters per second (m/s) — or 47 feet per minute — faster than those who received a placebo.
While the absolute mean walking speed in the Amvuttra group slightly declined over 18 months (-0.024 m/s), a pronounced decline in the external placebo group was about 10 times worse (-0.264 m/s).
Similar results were reported using the Rasch-built Overall Disability Scale (R-ODS) assessment, a questionnaire on the limitations of activity and social participation, with higher scores reflecting improvements. The mean score for Amvuttra-treated patients declined by 1.5 points, while the placebo group dropped by 9.9 points, a difference of 8.4 points favoring Amvuttra after 18 months.
At baseline, most patients in both groups had Karnofsky Performance Status (KPS) of 70%-80%, which classifies patients by functional impairment. This means that patients were either unable to engage in normal activity or work, or were able to participate in normal activity with effort.
By 18 months, there was a higher proportion of Amvuttra-treated patients than placebo-treated patients with stable (58.2% vs. 34.7%) or improved (13.1% vs. 8.1%) KPS scores, indicating a stable or improved ability to participate in normal activities.
Lastly, nutritional status was assessed using the modified body mass index (mBMI), which measures body fat adjusted by blood albumin protein levels to correct FAP-associated weight gain.
Nutritional gains were seen as early as three months with Amvuttra, as indicated by a mean 4-point increase in mBMI, compared with a 30.3 point decline in the placebo group.
By 18 months, these patients further improved to a mean mBMI of 25. By contrast, the external placebo group’s mBMI continued to decline to a mean of 115.7-points by 18 months, a 140.7-point worsening.
“Findings from the HELIOS-A study demonstrate that [Amvuttra] treatment over 18 months provides significant clinical benefits compared with the external placebo group in multiple measures of [quality of life] and physical function,” the researchers concluded.
“These benefits of [Amvuttra] were seen in the overall study population and were most pronounced in patients with earlier-stage disease at baseline, highlighting the importance of initiating effective treatment for ATTRv amyloidosis with polyneuropathy early in the course of disease,” they added.
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