October 6, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Cambridge, Massachusetts – Alnylam Pharmaceuticals dropped after the company announced it was discontinuing development of revusiran for hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM).
Essentially, more patients on the drug died than those receiving the placebo. “We’re very sad to report the outcome here,” Akshay Vaishnaw, the company’s chief medical officer, said in a call with investors. “In terms of causality, we don’t have an explanation for this finding.”
After receiving reports during the Phase II OLE study that several patients were developing or having worsening peripheral neuropathy, Alnylam requested a Data Monitoring Committee (DMC) evaluate its ENDEAVOUR Phase III trial. Although the committee didn’t find conclusive evidence of neuropathy related to the drug, due to the benefit-risk profile, it recommended they suspend dosing. Alnylam then reviewed unblinded data from the ENDEAVOUR trial and noted the increased death rate.
“Patient safety comes first,” said John Maraganore, Alnylam’s chief executive officer, in a 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 also has another drug, patisiran, which is currently in a Phase III trial for hATTR amyloidosis with polyneuropathy (hATTR-PN). The company indicates that the termination of the revusiran study doesn’t affect the patisiran study or any of its other investigational RNAi programs currently in development.
Company stock is currently trading for $70.30, although it traded for $78.09 on September 27. After hours trading went for about $41.
TheStreet Ratings team gave the stock a “sell” with a ratings score of D. It wrote, “Alnylam’s weaknesses include its deteriorating net income, disappointing return on equity, weak operating cash flow, generally disappointing historical performance in the stock itself and feeble growth in its earnings per share.”
Hereditary amyloidosis with cardiomyopathy is a disease where amyloid plaque, similar to that found in the brains of Alzheimer’s patients, accumulates in the heart and other organs. It can lead to heart failure. It is diagnosed in 6 to 10 Americans per million annually, according to the American Heart Association, although it is believed to be underdiagnosed.
Alnylam focuses on RNA interference (RNAi). This technology acts to prevent genes from manufacturing specific proteins. Revusiran was engineered to target the gene that makes the abnormal protein that causes amyloidosis.
In late September, Alnylam presented 10 posters and oral presentations about its GalNAc platform at the 12th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) in Montreal, Quebec. In one of the presentations, a Phase I/II study of ALN-AAT to treat AAT deficiency-associated liver disease (alpha-1 liver disease), three patients showed asymptomatic, transient increased liver enzymes. As a result, that study was halted.
“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,” the Company said in a statement. “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.”
The company has a fairly broad pipeline focused on three strategic therapeutic areas, including Genetic Medicines, Cardio-Metabolic Diseases, and Hepatic Infectious Diseases.
