FAP Patients Might Have New Treatment Before Year’s End, as Trial Data Show Patisiran’s Benefits

Patients with hereditary ATTR amyloidosis, also called familial amyloid polyneuropathy (FAP), might soon have a new medication to look forward to, as data from a recent Phase 3 trial of patisiran showed the treatment improved quality of life and reduced the impairment caused by nerve damage.

Alnylam Pharmaceuticals and Sanofi Genzyme, which jointly developed the drug, plan to seek U.S. regulatory approval by year’s end, and marketing approval in Europe shortly thereafter.

Patisiran is an RNAi therapy, meaning it blocks the production of messenger RNA —  intermediate molecules in the process of translating genetic information to a protein. Patisiran silences the messenger RNA of the disease-causing TTR (transthyretin) protein.

“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,” Alnylam CEO John Maraganore said in a press release. “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.”

The Phase 3 APOLLO trial (NCT01960348) recruited 225 FAP patients who had among them 39 distinct mutations causing the disease.

For every two patients who received patisiran, one was randomly given placebo infusions. After 18 months, those treated with patisiran had improved their neuropathy-related impairment — the trial’s primary goal.

But they also scored better on a quality of life assessment than those on placebo. In addition, all five secondary outcome measures were significantly better in patisiran-treated patients, including muscle strength, gait speed and autonomic symptoms. A questionnaire also showed better scores in a patient-reported outcome measure of daily living and disability.

“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 Dr. Elias Zerhouni, president of Sanofi’s global research and development division.

“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,” Zerhouni added. “We look forward to working with Alnylam to make patisiran available around the globe as quickly as possible.”

Importantly, the study showed that patisiran was safe and well tolerated. Researchers observed similar rates of adverse events — some of them severe — in patisiran-treated and control groups. This indicates that the adverse events had no connection to the treatment.

Also, only 7.4 percent of patients treated with patisiran stopped their treatment early, compared to 37.7 percent in the placebo group. In addition, 4.7 percent of those on patisiran stopped taking the drug due to an adverse event, compared to 14.3 percent in the control group.

“Patients living with hATTR amyloidosis face an inevitable and painful advancement of their debilitating disease,” said Dr. Akshay Vaishnaw, executive vice-president of research and development at Alnylam. “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.”

In addition to U.S. and European regulatory applications, Sanofi Genzyme is preparing to file applications in Japan, Brazil and other countries in the first half of 2018.