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Alnylam (ALNY) Execs Open Up About Patient Deaths in Abandoned Drug Trial

11/4/2016 6:35:36 AM

Alnylam Execs Open Up About Patient Deaths in Abandoned Drug Trial November 4, 2016
By Mark Terry, Breaking News Staff

On October 5, Cambridge, Mass.-based Alnylam Pharmaceuticals (ALNY) announced that it was discontinuing development of revusiran for hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM). The decision was made on the basis of unexpected patient deaths. At its third-quarter conference call the company provided more details.

Alnylam works in the field of RNA interference (RNAi). This is based on how genes are turned on and off. ATTR amyloidosis is a progressively debilitating and often fatal disease caused by an accumulation of transthyretin (TTR) in peripheral tissues. The TTR protein is mostly produced in the liver and normally carries vitamin A.

On October 5, the company disclosed that there had been 18 patient deaths in the trial. During the conference call, the company’s chief medical officer, Akshay Vaishnaw, said that there had been another death. Of the original 18 deaths, 16 were receiving revusiran.

The trial has 206 patients, all with ATTR cardiomyopathy. They were randomized two-to-one to receive revusiran versus placebo. Vaishnaw said there was a “perfectly balanced distribution” of the deaths between the active drug arm and the placebo arm.

Although the data monitoring committee recommended the trial be halted, the company has said “there was no conclusive evidence of drug-related peripheral neuropathy” that would have caused the deaths.

“We have established a team to evaluate all the revusiran data,” Vaishnaw said during the call. “To the extent possible, we intend to provide you with an update on our progress at our upcoming R&D day in December, but you should expect that our evaluation may take months to reach conclusive results.”
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Investors are concerned that the safety issues for revusiran cast a shadow over all of Alnylam’s RNAi technology. The company has more than half-a-dozen other compounds in clinical trials.

That’s a realistic concern. On September 30, the company presented 10 posters and oral presentations at the 12th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) in Montreal, Quebec. In that group, it presented data from its Phase I/II study of ALN-AAT to treat AAT deficiency-associated liver disease (alpha-1 liver disease), where three patients showed asymptomatic, transient increased liver enzymes. As a result, that trial was halted.

In a statement, the company said, “Since the target patient population for ALN-AAT has established liver disease, Alnylam plans to advance a follow-on molecule targeting a different sequence for further development. Specifically, the Company is finalizing selection of a new Development Candidate—ALN-AAT02—and plans to rapidly advance this compound towards the clinic, with a planned CTA filing in 2017.”

In 2014, Alnylam developed an alliance with Sanofi Genzyme (SNY) to accelerate and broaden RNAi therapeutic development. Alnylam holds product rights in North America and Western Europe. Sanofi Genzyme picked up the right to access specific programs in Alnylam’s current and future Genetic Medicines pipeline, including ALN-AAT in the rest of the world through the end of 2019.

Alnylam stock has taken a huge hit recently. Shares traded on September 27, 2016 for $78.09. They plunged to $36.21 on October 6 and are currently trading for $33.63. Shares had a yearly high of $108.96 on December 4, 2015.

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