The US Food and Drug Administration has approved Alnylam’s RNAi therapeutic Onpattro for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis.

hATTR amyloidosis is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene, which cause abnormal amyloid proteins to accumulate and damage body organs and tissue, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy.

Alynylam has previously said that the condition represents “a major unmet medical need with significant morbidity and mortality,” affecting around 50,000 people worldwide who have a life expectancy of 2.5 to 15 years from symptom onset. The only approved treatment options until now have been liver transplantation for early stage disease and tafamidis.

Data from the Phase III APOLLO trial, which enrolled 225 hATTR amyloidosis patients with polyneuropathy, representing 39 genotypes, at 44 study sites in 19 countries around the world, showed that at 18 months the mean change from baseline in the modified neuropathy impairment score (mNIS+7) was significantly lower in the Onpattro (patisiran) group as compared with placebo.

Patients treated with Onpattro had a mean 6.0-point decrease (improvement) in mNIS+7 score from baseline compared to a mean 28.0-point increase (worsening) for patients in the placebo group, resulting in a mean 34.0-point difference relative to placebo, after 18 months of treatment.

Also, patients in the treatment group experienced improvement in quality of life compared to placebo, as assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy, while all five other secondary endpoints also demonstrated statistically significant favourable differences in the treatment arm, including a 10-meter walk test, assessing gait speed and muscle strength.

“FDA approval of Onpattro represents an entirely new approach to treating patients with polyneuropathy in hATTR amyloidosis and shows promise as a new era in patient care,” said John Berk, Associate Professor of Medicine at Boston University School of Medicine and assistant director of the Amyloidosis Center at Boston University School of Medicine.

“Given the strength of the APOLLO data, including data showing the possibility of halting or improving disease progression in many patients, Onpattro holds tremendous promise for people living with this disease.”

Onpattro has also been filed in Europe. Pending regulatory approvals, Alnylam will commercialise the drug in the US, Canada and Western Europe, with Sanofi Genzyme commercialising the product in the rest of the world.