Sanofi, Alnylam’s ATTR amyloidosis study meets main goal

Sanofi’s speciality care unit Genzyme together with an RNAi therapeutics company Alnylam Pharmaceuticals, announced Wednesday that the APOLLO Phase 3 study of patisiran, an investigational RNAi therapeutic being developed for patients with hereditary ATTR amyloidosis with polyneuropathy, met its primary efficacy endpoint and all secondary endpoints.

The primary endpoint for the study was the change from baseline in the modified neuropathy impairment score (mNIS+7) at 18 months.  The key secondary endpoint was improvement in quality of life assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN).

“We are very proud to report the first ever positive Phase 3 results for an RNAi therapeutic, marking the potential arrival of an entirely new class of medicines. This moment is the culmination of a 15-year journey of tireless work by countless contributors who have overcome enormous scientific and business challenges to make RNAi therapeutics a reality,” said John Maraganore, Chief Executive Officer of Alnylam.

The APOLLO trial enrolled 225 hATTR amyloidosis patients with polyneuropathy, representing 39 genotypes, at 44 study sites in 19 countries around the world.

At 18 months, the mean change from baseline in mNIS+7 was significantly lower in the patisiran group as compared with placebo (p less than 0.00001).

All five other secondary endpoints also demonstrated statistically significant favorable differences in the patisiran arm compared to placebo (p less than 0.001). These were: assessing muscle strength,
a patient reported outcome measure of daily living and disability, assessing gait speed, assessing nutritional status, and assessing autonomic symptoms.

Furthermore, the overall safety profile of patisiran was encouraging. The frequency of deaths in the study was similar in the patisiran (4.7 percent) and placebo (7.8 percent) arms.

Akshay Vaishnaw, Executive Vice President, R&D of Alnylam, said: “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.”

Alnylam expects to file its first New Drug Application in late 2017 and first Marketing Authorisation Application shortly thereafter. Sanofi Genzyme is currently preparing for regulatory filings for patisiran in Japan, Brazil and other countries, to begin in the first half of 2018.  Alnylam plans to launch patisiran in the U.S., Canada and Western Europe, with Sanofi Genzyme selling the product in the rest of the world.

“This is a significant milestone that supports our belief that RNAi therapeutics have the potential to become an innovative new class of medicines for patients with rare genetic diseases,” said Elias Zerhouni, M.D., President, Global R&D, Sanofi. “The APOLLO data suggest that patisiran could help improve the lives of people living with hATTR amyloidosis with polyneuropathy, a patient population in urgent need of additional treatment options. We look forward to working with Alnylam to make patisiran available around the globe as quickly as possible.”