European Commission approved Alnylam’s AMVUTTRA, an RNAi therapeutic for treating hATTR amyloidosis with polyneuropathy
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After grabbing FDA approval in June, Alnylam Pharmaceuticals has recently received European Commission approval to market AMVUTTRA in the EU. AMVUTTRA, an RNAi based therapeutic, is indicated for treating hereditary transthyretin-mediated (hATTR) amyloidosis with stage 1 or 2 polyneuropathy.
hATTR amyloidosis is a rare, genetic, and protein-misfolding disease affecting multiple organs and tissues with key clinical presentations: polyneuropathy (damage of peripheral nerves) and cardiomyopathy. hATTR amyloidosis affects 50,000 people worldwide, with a median survival of 4.7 years post-diagnosis. The disease is caused by mutations in the transthyretin (TTR) gene and is characterized by the extracellular deposition of amyloid fibrils. Under normal conditions, TTR is a homotetramer that transports thyroxine and Vitamin A in the blood and cerebrospinal fluid. However, In hATTR amyloidosis, the mutated TTR impairs the stability of the tetramers resulting in dissociation into monomers. This leads to misfolding, aggregation, and deposition of TTR amyloid fibrils in the extracellular region.
AMVUTTRA (vutrisiran) is an RNAi therapeutic targeted to block the production of TTR protein by silencing the mRNA. It is expected to block both wild-type and mutated forms in the liver. HELIOS-A (NCT03759379) is a global phase 3, open-label study to assess the efficacy and safety of AMVUTTRA in patients with hATTR amyloidosis. AMVUTTRA was compared with Patisiran (FDA approved) and an external placebo from the APOLLO study (NCT01960348). The primary endpoint was to measure the modified neuropathy impairment score (mNIS) +7 – an assessment to quantify decreased muscle weakness, muscle stretch reflexes, sensory loss, and autonomic impairment – from the baseline.
Key results showed that AMVUTTRA significantly improved the mNIS +7 scores compared to external placebo at months 9 and 18 in more than 50% of the patients. Additionally, there was a rapid and sustainable reduction in serum TTR levels. AMVUTTRA has the advantage of a quarterly subcutaneous administration compared to once every three weeks for Patisiran. Patients could start seeing the benefits within nine months of the treatment. The most seen adverse reactions following the 18-month study were joint stiffness and pain in the arms and legs.
Alnylam Pharmaceuticals, founded in 2002, focuses on translating RNAi-mediated therapeutic approaches to multiple diseases, including rare genetic, hepatic infectious, cardio-metabolic and central nervous system diseases. Currently, AMVUTTRA is also under review by the Brazilian health regulatory agency and Japanese authority, PMDA.
