Just three months ago, gene-silencing specialist Alnylam was pummelled after deaths in a phase 3 clinical trial forced it to abandon its revusiran candidate for hereditary ATTR amyloidosis. Now, it is hoping to file its new lead candidate by the end of the year.
Chief executive John Maraganore said at the J.P. Morgan Healthcare Conference that the company has moved on from that disappointment and is anticipating its first phase 3 data readout for new lead candidate patisiran—also for ATTR amyloidosis patients—in September.
ATTR amyloidosis is complication seen in patients with familial amyloidotic polyneuropathy (FAP), a rare genetic defect that can lead to deadly protein buildups that can damage nerve tissue.
"By the end of 2017 we will have three programs in late-stage development and one program in registration," he told investors, putting it on course to meet its goal of having multiple products on the market by 2020.
He insisted that the decision to drop the revusiran program after more deaths were seen in the treatment than placebo arm has no bearing on the company's gene-silencing platform and its other pipeline candidates. Investors have been nervy after the revusiran withdrawal was followed by news of patient death in a trial of one of Alnylam's partnered gene-silencing drugs, The Medicine Company's cholesterol-lowering candidate inclisiran.
While the ENDEAVOUR study of revusiran remains blinded, indications are that the 19 patients who died in the study—mainly from heart-related issues—tended to be sicker at enrolment, according to Maraganore.
"All the evidence to date has been dispositive of any platform indications," he told investors at the JP Morgan event, pointing out also that revusiran was an earlier generation compound given at much higher doses than Alnylam's current programs. He also said that experts have suggested that the inclisiran death (caused by an aneurysm) is unlikely to be drug-related.
"We've now generated a comprehensive safety database of over a thousand patients and three years of dosing across 10 clinical programs—overall we're encouraged by the safety profile we are seeing," said Maraganore.
Returning to patisiran, he noted the drug is currently being tested in the 225-patient APOLLO study, which is comparing the drug to placebo over an 18-month period, and is statistically overpowered so has a good chance of revealing any benefit.
The drug's main rival in ATTR amyloidosis is Ionis Pharmaceuticals' IONIS-TTR Rx candidate, which is also in phase 3 and due to generate results in April, according to analysts at Jefferies. Ionis has had its own safety scare after severe declines in platelets were seen in patients treated with another GlaxoSmithKline-partnered candidate.
Alnylam is trying to stay ahead of the pack by also bringing forward another ATTR amyloidosis candidate—TTRsc02—which could allow dosing just once every three months, while most drugs currently in development require weekly injections.
Meanwhile, Alnylam's other pipeline candidates include porphyria drug givosiran—with data from a Phase I/II trial due in June, and fitusiran for hemophilia in Phase II testing. A phase 3 program for givosiran designed to support regulatory approvals is due to start later this year, while the ATLAS program for fitusiran—including three pivotal studies—will get underway shortly.