Vutrisiran, sold under the brand name Amvuttra, is a medication used for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.
[5] Vutrisiran is generally well tolerated but side effects can include injection site reactions, fatigue, arthralgia, dyspnea, diarrhea and musculoskeletal pains.
These potent and durable pharmacodynamic properties of vutrisiran, together with an acceptable safety profile, prompted further evaluation in a phase I clinical study.
[18] Vutrisiran was found to be well tolerated, established a good safety profile and elicited rapid robust and durable TTR reduction.
[20] Vutrisiran treatment resulted in rapid (≤3 weeks) and sustained reduction in serum TTR levels over 18 months, similar to what was observed in the patisiran group.
Following 18 months of vutrisiran treatment, steady-state mean (SD) peak and trough serum TTR reductions from baseline were 87.6% and 81.0%, respectively.
[10] A subcutaneous dose of 25 mg vutrisiran every 3 months caused similar or greater efficacy than patisiran given as IV infusion three times a week.
[18] Vutrisiran significantly improved multiple disease-relevant outcomes versus placebo, with an acceptable safety profile.
[16] The ongoing extension period of HELIOS-A will assess long-term safety and efficacy with continued Q3M vutrisiran treatment, or an alternative every 6 months dosing regimen.
[21] A study whose results are awaited is the phase III HELIOS-B (NCT04153149) randomized, double-blind, placebo-controlled trial, in which patients with TTR-related amyloid heart disease, both wild-type and mutated forms, are enrolled to evaluate the possible effects of the drug in terms of cardiac involvement.
The primary end point will evaluate the efficacy of vutrisiran in the composite outcome of reducing all-cause mortality and recurrent cardiovascular hospitalization.
The majority of adverse events in the phase I trial of vutrisiran were mild, and included nasopharyngitis, headache, diarrhoea and nausea, and injection site reactions.
[16] HELIOS-A trial also reported encouraging safety and tolerability, with the majority of adverse events being mild or moderate 10 and no drug- related discontinuations or deaths occurred.
[16] AEs occurring in (≥ 10%) of patients receiving vutrisiran included falls, pain in extremity, diarrhea, peripheral edema, urinary tract infection, arthralgia, and dizziness; all of which, except pain in extremity and arthralgia, occurred at a similar or lower rate than in the external placebo group.
Four vutrisiran recipients (3.3%) developed antidrug antibodies (ADAs) that were low and transient with no evidence of an effect on clinical efficacy, safety, pharmacokinetics or pharmacodynamic parameters.