An investigational RNAi therapeutic being developed by Sanofi Genzyme and Alnylam Pharmaceuticals has hit targets in a late stage trial involving patients with hereditary ATTR amyloidosis with polyneuropathy.

The companies said the Phase III APOLLO trial of patisiran met its primary efficacy endpoint and all secondary endpoints, paving the way to a regulatory filing in the US later this year and the EU in early 2018.

Hereditary transthyretin (TTR)-mediated (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.

According to Sanofi and Alynylam, 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. Currently, the only approved treatment options are liver transplantation for early stage disease and tafamidis.

The APOLLO trial enrolled 225 hATTR amyloidosis patients with polyneuropathy, representing 39 genotypes, at 44 study sites in 19 countries around the world. Patients were randomised 2:1 to patisiran or placebo, with patisiran administered intravenously at 0.3 mg/kg once every three weeks for 18 months.

At 18 months, the mean change from baseline in the modified neuropathy impairment score (mNIS+7) was significantly lower in the patisiran group as compared with placebo, thus meeting the study’s primary goal.

Also, patients in the patisiran group experienced improvement in quality of life compared to placebo, as assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN), 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.

The firms also noted that the overall safety profile of patisiran was “encouraging”, with patisiran and placebo arms having similar frequencies of adverse events (96.6 percent and 97.4 percent, respectively) and serious adverse events (36.5 percent versus 40.3 percent, respectively).

“We believe the very encouraging APOLLO data demonstrate the potential for investigational patisiran to help improve the lives of hereditary ATTR amyloidosis polyneuropathy patients. Our immediate objective is now to submit these data to global health authorities,” said Akshay Vaishnaw, executive vice president, R&D of Alnylam.

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.