Alnylam's star RNAi drug keeps the pace on the way to Phase III

Alnylam CEO John Maraganore

Alnylam's ($ALNY) lead RNAi treatment continued to prevent nerve damage tied to a rare disease in an ongoing Phase II study, paving the path for late-stage development.

The drug, patisiran, is a treatment for transthyretin-mediated amyloidosis, or ATTR, in patients with familial amyloidotic polyneuropathy (FAP), a rare genetic defect that can lead to deadly protein buildups that damage nerve tissue. In an open-label study, the 20 FAP patients who received patisiran for 12 months reported an average 2.5-point decrease in a measure called modified Neuropathy Impairment Score, designed to quantify nerve function. The study has no placebo arm, but Alnylam says historical FAP data would suggest a 13- to 18-point increase in impairment over the same period, illustrating patisiran's promise.

And the drug, which is designed to reduce serum levels of transthyretin (TTR), notched a sustained TTR knockdown above 80% at 16 months, which, coupled with the neuropathy improvement, affirms the guiding hypothesis behind patisiran's development, according to Alnylam.

The results sent Alnylam's shares up about 10% on Tuesday as investors cheered the drug's progress in FAP. Last year, the biotech unveiled 6-month results from the same study in which patisiran clocked a mean 1-point reduction in neuropathy impairment, and the latest data suggest a durable benefit over time, investigator Dr. David Adams said.

"In particular, the possibility of halting neuropathic progression over 12 months of treatment is promising in light of the rapid increase in neuropathy impairment scores observed in analysis of other historical data sets," Adams, coordinator of the French Reference Center for FAP, said in a statement. "If these results are replicated in a randomized, double-blind, placebo-controlled study, I believe that patisiran could emerge as an important treatment option for patients suffering from this debilitating, progressive and life-threatening disease."

Now it's on Alnylam and partner Sanofi ($SNY) to follow through on that promise. The two are currently recruiting such a Phase III trial with a primary endpoint of improving Neuropathy Impairment Score from baseline at 18 months. In the meantime, Alnylam is keeping its open-label study rolling, expecting to report 18-month data later this year.

The drug is among of a slew of pipeline therapies Alnylam is working on with Genzyme. The Sanofi unit first stepped in on patisiran in 2012, paying $22.5 million up front for the Asian rights to the treatment with the promise of undisclosed milestones down the road. Then, last year, Sanofi took a $700 million stake in Alnylam in an expression of faith in the biotech's RNAi potential, a deal that expanded Genzyme's share of patisiran to include every territory outside of Western Europe and North America.

- read the results