A phase 3 trial of Alnylam’s patisiran has hit all of its primary and secondary endpoints. The clean sweep is a big win for Alnylam and the Sanofi-partnered gene silencing drug, which is now set to be put before regulators around the end of the year.

The data mark the culmination of almost 20 years work—and about 15 years work at Alnylam— to refine and validate the use of RNAi to silence genes and, in doing so, treat disease. Alnylam has ridden out the ebbs and flows in excitement about the novel approach to treating disease and emerged with phase 3 data that position it to create a new corner of the drug industry.

Alnylam CEO John Maraganore, Ph.D., acknowledged the significance of the data.

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“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,” he said in a statement.

Investigators enrolled 225 hereditary ATTR amyloidosis patients representing 39 genotypes in the trial. Two-thirds of participants received 0.3 mg/kg of patisiran intravenously once every three weeks for 18 months. The rest got placebo.

Patisiran blew placebo out of the water in terms of affect on the modified neuropathy impairment score, resulting in a p value of less than 0.00001. That meant the trial met its primary endpoint.

The divergence between patisiran and placebo was similarly pronounced against a key secondary endpoint that assessed the quality of life. Patisiran also beat placebo on the five other secondary endpoints, showing the drug affects muscle strength, walking speed, disability and other factors relevant to patients with hereditary ATTR amyloidosis.

Patisiran also emerged from the phase 3 with an acceptable safety profile. Peripheral edema and infusion-related reactions were more common in the patisiran arm. Many of these adverse events were of mild-to-moderate severity, though, and the proportion of deaths and dropouts was lower in the patisiran arm than placebo cohort.

Alnylam is now gearing up for its next challenges, namely persuading regulators of the merits of patisiran and then commercializing the drug. The biotech is aiming to get a filing to the FDA by the end of the year, with a European submission following shortly thereafter. Sanofi is responsible for filings in Japan, Brazil and other countries. The first of those submissions is due to land in the first half of next year.

Analysts at Leerink said in a note to clients this morning: "In the wake of the recent fitusiran setback - and also the discontinuation of revusiran last fall - the positive patisiran result with seemingly clean safety is likely to improve sentiment significantly. Specifically, the mortality rate in the patisiran arm (4.7%) was lower than that seen on placebo (7.8%); given the small N it's debatable whether or not this constitutes a true improvement, but in any case it's very encouraging with respect to RNAi safety.

"Ironically, more recent setbacks for ALNY (revusiran and then fitusiran) have come from next-gen RNAi compounds that do not utilize the older, lipidnanoparticle technology, which is the case for patisiran. But even despite this difference, we expect the result this morning to read positively on the platform and technology overall."

Shares in Alnylam jumped 25% in premarket trading. The gains added to the 100% increase in the stock seen over the first nine months of 2017.