Alnylam’s RNAi therapeutic Onpattro has been approved for use in Europe to treat Hereditary Transthyretin-Mediated (hATTR) Amyloidosis (hATTR amyloidosis) in adults with Stage 1 or Stage 2 polyneuropathy.

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.

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.

On the safety side, the incidence and severity of adverse events were similar in patients receiving Onpattro and placebo. The most common adverse events that occurred more frequently in the treatment group were peripheral oedema and infusion-related reactions.

“Patisiran has been shown to improve polyneuropathy, quality of life and activities of daily living,” said Theresa Heggie, head of Europe, Alnylam Pharmaceuticals. “This is the start of a new chapter in the treatment of this rare, rapidly progressive, fatal disease.”

“Until recently, patients diagnosed with hereditary ATTR amyloidosis faced an uncertain future. A lack of treatments to halt or reverse the progression of disease resulted in a gradual and inescapable decline in their day-to-day functioning, placing a heavy burden not just on the patient themselves but on their partners and families, many of whom end up being full time carers,” noted Professor Philip Hawkins, National Amyloidosis Centre, Division of Medicine, and University College London Medical School, Royal Free Hospital, UK.

“Patisiran has the potential not only to transform these patients’ lives but to change the way in which we think about and treat hereditary ATTR amyloidosis.”

The drug was also approved by US regulators earlier this month.