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October 6, 2016

After 18 Deaths in Phase III, Alnylam Halts Revusiran Development

  • Alnylam Pharmaceuticals is halting development of revusiran following a Phase III trial of the RNA interference (RNAi) candidate in which 18 patients died.

    The company said in a statement it was abiding by a recommendation of the data-monitoring committee for the Phase III ENDEAVOUR trial assessing revusiran in patients with the rare disease hereditary transthyretin-related amyloidosis (hATTR) with cardiomyopathy (hATTR-CM).

    The committee said data from the trial found “an imbalance of mortality in the revusiran arm as compared to placebo."

    In a conference call late yesterday, Alnylam acknowledged that 18 of ENDEAVOUR’s 206 participants died of heart-related issues, adding that none of the deaths were drug-related. However, the company did not detail how many patients died in each of the trial’s arms.

    “In terms of causality, we don’t have an explanation for these safety findings,” Akshay Vaishnaw, Alnylam CMO and evp of R&D, said on the conference call.

    The data monitoring committee reviewed data from ENDEAVOUR as well as reports from the Phase II open-label extension (OLE) study of new-onset or worsening peripheral neuropathy. The committee did not find conclusive evidence for a drug-related neuropathy signal in ENDEAVOUR, but told Alnylam that the benefit–risk profile for revusiran no longer supported continued dosing, the company said.

    "Patient safety comes first,” Alnylam CEO John Maraganore, Ph.D., said in the statement. “We have stopped all dosing and are actively monitoring patients across revusiran studies to ensure their safety. We will also continue to evaluate ENDEAVOUR data to understand the potential cause of these findings.”

    Alnylam said the decision to halt development of revusiran would not affect any of its eight development programs. These include its program to develop patisiran, now in Phase III development for hATTR with polyneuropathy (hATTR-PN), and its ALN-PCSsc program partnered with The Medicines Company.

    In the eight programs, Alnylam said, “there is no evidence of a drug-related neuropathy signal” in over 800 treated subjects and patients with exposure of up to 34 months.

    News of the trial deaths and halt to revusiran development led to an investor selloff of company stock, with Alnylam’s share price falling 47% since yesterday’s close of $70.30, to $37.04 as of 9:33 a.m.

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