Real-world study finds Amvuttra helps keep hATTR-PN, life quality stable
All patients in small study prefer shots to infusions, citing convenience
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Six months of treatment with Amvuttra (vutrisiran) appears to maintain or slightly improve clinical status and quality of life among adults with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), according to a small real-world study in Spain.
None of the results were statistically significant, the researchers noted, but the team highlighted both a key qualification and what they called a “meaningful” benefit: First, the participants in the study had worse disease than patients in an earlier clinical trial, and second, a trend toward stable or eased neurological symptoms was seen.
“Although our results did not reach statistical significance, we observed no deterioration in quality of life and evidence of clinical stability,” the scientists wrote, adding that their patient population was “more pretreated and had greater disease burden” than that of the clinical trial that led to Amvuttra’s approval for hATTR-PN.
Still, “long-term real-world studies are warranted to confirm these findings,” the researchers wrote.
The study, “Quality of life and effectiveness of vutrisiran as treatment for hereditary transthyretin amyloidosis,” was published as a brief report in Farmacia Hospitalaria by two researchers in Spain.
hATTR-PN is a form of hereditary transthyretin amyloidosis, in which mutations in the TTR gene lead to the production of a faulty transthyretin protein that forms toxic clumps that accumulate in tissues and damage them.
Also known as familial amyloid polyneuropathy, hATTR-PN is marked by the buildup of these toxic clumps, or aggregates, mainly in the peripheral nerves, or those outside the brain and spinal cord. That buildup leads to polyneuropathy, or damage to multiple nerves. Some patients may also accumulate toxic transthyretin clumps in the heart muscle, causing damage known as cardiomyopathy.
Alnylam Pharmaceuticals’ Amvuttra, administered via subcutaneous, or under-the-skin, injections every three months, works by reducing transthyretin production, thereby preventing its buildup and slowing disease progression.
The therapy is approved in the U.S. for adults with hATTR-PN, and in Europe for those who have stage 1 or stage 2 polyneuropathy. It is also approved in both the U.S. and Europe for adults with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), hereditary or not.
Investigating Amvuttra use, benefits in the real world
Data from the Phase 3 HELIOS-A clinical trial (NCT03759379), which supported Amvutra’s approvals for hATTR-PN, showed that the therapy significantly reduced neurologic impairments and overall disability, while improving quality of life related to nerve damage, over 1.5 years.
While noting the benefits seen in the trial, the researchers argued that “the evaluation of innovative therapies must extend beyond clinical efficacy to consider their impact on patients’ quality of life.”
“In the context of [hereditary transthyretin amyloidosis], a rare and progressive condition, patient-reported outcomes are essential to capture the real-world benefits of treatment,” the researchers wrote.
To better understand the real-world benefits of Amvuttra for quality of life, the duo examined how hATTR-PN patients responded to six months of treatment in routine clinical practice. The main goal was to assess changes in the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire, which measures patient-reported quality of life based on polyneuropathy symptoms and their impact on daily activities.
“As a secondary objective, we describe effectiveness, safety and patient treatment preferences with [Amvuttra],” the researchers wrote.
The study involved 25 hATTR-PN patients — 14 men and 11 women — with a mean age of 66. All began treatment with Amvuttra between November 2023 and May 2024. Treatment was started a mean of six years after the patients’ diagnoses. Slightly more than half of the participants tested positive for Val30Met, the most common mutation causing hATTR-PN.
A total of 12 (48%) had Coutinho stage 1, meaning they had abnormal sensations or weakness, but could still walk unaided. The remaining 13 had Coutinho stage 2, meaning they no longer could walk without assistance.
Nearly all participants (96%) had received previous treatment. More than one-third switched from tafamidis, approved in Europe for hATTR-PN under the brand name Vyndaqel, and marketed in the U.S. as Vyndamax for ATTR-CM alone, mainly because their disease continued to worsen.
More than one-half switched from Onpattro (patisiran), Amvuttra’s predecessor that is approved for hATTR-PN, and one switched from Tegsedi (inotersen), an hATTR-PN-approved therapy now discontinued, mostly for convenience reasons.
Quality of life seen to improve over 6 months of treatment
Over six months of treatment with Amvuttra, Norfolk QOL-DN scores decreased by a median of six points, from 54 to 48, indicating better quality of life. Although this numerical improvement was not statistically significant, it suggests that quality of life was at least maintained, according to the researchers.
Neurological function was assessed using the Neuropathy Impairment Score (NIS), a clinical scale that measures muscle strength, reflexes, and sensation. The median NIS decreased from 41 to 22 points after six months. While this change was not statistically significant, a lower NIS indicates less impairment, suggesting a trend toward neurological stability or improvement.
In the blood, the transthyretin protein was either maintained at very low levels or reduced to undetectable levels in all participants. Overall, 14 patients already had undetectable TTR before starting Amvuttra, mostly due to previous treatment with Onpattro. The remaining patients showed reductions after switching to Amvuttra.
Heart health was monitored using blood NT-proBNP levels, a marker of heart damage. Median NT-proBNP decreased from 464 to 345 picograms/mL after six months. Although not statistically significant, this finding suggests that heart function remained stable.
[Amvuttra] has demonstrated potential, both in [a clinical] trial and in our [patient group], where even modest improvements or stabilization in patient-reported outcomes may represent meaningful clinical benefit and improve or maintain quality of life.
All 15 patients surveyed preferred subcutaneous injections to intravenous, or into-the-vein, infusions, stating that this mode of administration was more convenient, required less hospital time, and involved less frequent dosing. The mean score reflecting the positive impact of this new administration method on daily life was 4 of 5.
No treatment-related side effects were reported during follow-up, indicating a favorable safety profile.
Amvuttra “has demonstrated potential, both in HELIOS-A trial and in our [patient group], where even modest improvements or stabilization in patient-reported outcomes may represent meaningful clinical benefit and improve or maintain quality of life,” the researchers wrote, nonetheless adding that “long-term real-world studies are needed to confirm these findings.”
