FDA Approves RNAi Therapeutic Vutrisiran for hATTR Amyloidosis

A rapidly progressive, fatal rare disease called hereditary transthyretin-mediated (hATTR) amyloidosis has gained a new approved therapy with the favorable decision by the US Food and Drug Administration (FDA).

While this condition only has a few treatment options, vutrisiran (Amvuttra) is the first and only FDA-approved treatment that’s demonstrated reversal in neuropathy impairment with subcutaneous administration once every 3 months.

Phase 3 Data

Positive 9-month results provided by the HELIOS-A phase 3 study supported the approval. In the trial, vutrisiran significantly improved the signs and symptoms of polyneuropathy in adults. More than 50% of patients treated with the RNAi therapeutic experienced halting or reversal of their disease manifestations.

Additionally, vutrisiran met all primary and secondary endpoints with clinically significant outcomes, not only for polyneuropathy, but also for quality of life and gait speed relative to external placebo.

“The FDA approval of AMVUTTRA is very encouraging for the hATTR amyloidosis community, who need additional therapies to address the polyneuropathy of this progressive, life-threatening, multisystem disease,” Michael Polydefkis, MD, MHS, Professor, Johns Hopkins Neurology and HELIOS-A Study Investigator said in a statement.

“AMVUTTRA is a new therapeutic option that has demonstrated the potential to halt or reverse polyneuropathy progression in patients with an acceptable safety profile,” he continued, “along with an infrequent, subcutaneous dosing regimen that may also help to improve the disease management experience for patients.”

Unmet Needs of hATTR Amyloidosis

Hereditary transthyretin-mediated amyloidosis affects approximately 50,000 people worldwide. Once diagnosed with the inherited disease, the median survival is 4.7 years. For patients also presenting with cardiomyopathy that number reduces to 3.4 years of survival.

A variant or mutation in the TTR gene is what causes hATTR amyloidosis. The TTR protein is mainly produced in the liver and normally serves as a carrier for vitamin A. However, variants in the gene result in abnormal amyloid proteins that accumulate and damage body organs and tissue.

This can occur in the peripheral nerves and heart, therefore initiating intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy, among other disease manifestations. The significant morbidity and mortality that affects this population indicates a major unmet medical need.

The Advancing Frontier of RNAi Therapy

RNA interference, or RNAi, is a natural cellular process of gene silencing. According to Alynylam Pharmaceuticals, the developers of vutrisiran, RNAi is a promising and rapidly advancing frontier in the biology and drug development landscape right now.

RNAi therapeutics work by harnessing the natural biological process of RNA interference that occurs within the cells. Alnylam’s RNAi therapeutic platform consists of small interfering RNA (siRNA), or the molecules that mediate RNAi and silence messenger RNA (mRNA), known as the genetic precursors that encode for disease-causing proteins–preventing them from being made.

This RNAi therapeutic platform “functions upstream of today’s medicines” with its revolutionary approach and potential to transform the care of patients with genetic diseases.