Alnylam Stock Catapults as Genetic Disease Drug Meets All Phase III Goals

September 20, 2017
By Alex Keown, BioSpace.com Breaking News Staff

CAMBRIDGE, Mass. – Positive Phase III data for Alnylam ’s RNA interference treatment for hereditary ATTR amyloidosis with polyneuropathy has caused shares of company stock to spike more than 23 percent in premarket trading.

This morning, the company announced its Phase III Apollo study for patisiran met its primary efficacy endpoint and all secondary endpoints. Alnylam said patients on the patisiran arm fared significantly better against placebo. At 18 months, the mean change from baseline in mNIS+7 was significantly lower in the patisiran group as compared with placebo, Alnylam said. Trial data shows mean and median changes in mNIS+7 impairment scores for patisiran patients were both negative values. That indicates an overall improvement in the majority of patients compared with baseline, Alnylam said.

Based on the positive results, Alnylam and its developmental partner Sanofi plan to file for regulatory approval by the end of the year. Sanofi Genzyme is currently preparing for regulatory filings for patisiran in Japan, Brazil and other countries, to begin in the first half of 2018. Investors and company leaders are breathing a sigh of relief as Alnylam’s long journey to develop RNAi treatments appears to be paying off.

Alnylam Chief Executive Officer John Maraganore said the positive data is the “culmination of a 15-year journey of tireless work.” Now RNAi therapeutics are a reality, he said. RNAi is a natural mechanism of gene silencing.

“This is an incredibly exciting milestone for Alnylam and RNAi, and most importantly for patients and their treating physicians and families. We extend our deepest gratitude to all the patients, investigators and study staff who participated in the Apollo study – they made this important scientific progress possible,” Maraganore said in a statement this morning.

TTR amyloidosis is a severe, progressive and fatal disease with multiple overlapping clinical manifestations. There are three forms of TTR amyloidosis: familial amyloid polyneuropathy, FAP, familial amyloid cardiomyopathy, FAC, and wild type (wt)-TTR amyloidosis. The disease is caused by the accumulation of misfolded TTR protein in a broad range of tissues and organs, including peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to organ failure and eventually death.

Elias Zerhouni, head of Sanofi’s global R&D team, added that the results from the Apollo trial “supports our belief that RNAi therapeutics have the potential to become an innovative new class of medicines for patients with rare genetic diseases.” He said trial data indicates 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.”

Alnylam’s RNAi therapies have gone through a wild ride over the years of development. Last year, Alnylam announced it was discontinuing development of revusiran for hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM) following patient deaths.

As Alnylam investors celebrate the positive data this morning, investors in rival RNAi company Ionis Pharmaceuticals are not. Shares of that company are down about 10 percent in early trading. Ionis has seen several setbacks with its RNAi therapy targeting TTR amyloid cardiomyopathy, which includes patients with familial amyloid cardiomyopathy (FAC) and patients with wild-type transthyretin amyloidosis (wt-TTR amyloidosis).

While Alnylam celebrates the Apollo trial, the company saw a setback earlier this month when it suspended development of its Phase II fitusiran trial for hemophilia A following the death of a patient. The patient died from a thrombotic event and the company said it was suspending the trial pending further investigation.