- Alnylam Pharmaceuticals Inc. has halted clinical development for a main pipeline asset as the company investigates a recent patient death.
- The patient in question was enrolled in a mid-stage open label extension (OLE) study testing fitusiran as a treatment for moderate-to-severe hemophilia A or hemophilia B. He was hospitalized due to severe headache, and later died from a clot in one of the blood flow channels leading to his brain.
- Though it claimed the patient death wasn't related to fitusiran, Alynylam has stopped dosing patients in all investigations of the drug — including the Phase 2 OLE study and the recently initiated Phase 3 ATLAS program — until more information is known and a risk mitigation strategy is put into place.
It's almost deja vu for Alnylam. Around this time last year, the company faced another safety-related setback when a review of a late-stage study evaluating its drug for hereditary ATTR amyloidosis, revusiran, showed an imbalance in patient deaths between the trial's experimental and placebo arms.
A deeper investigation into why the imbalance existed came up mostly empty handed, though Alnylam noted that the evaluation showed no evidence revusiran caused cardiotoxicity and that safety worries shouldn't extend to its other RNA-focused programs.
"Importantly, we continue to remain confident that the findings with revusiran, a first-generation GalNAc-conjugate do not read through to the rest of our GalNAc platform and we believe recently reported data from across our pipeline continue to strengthen this confidence," Alnylam CEO John Maraganore said during the company's most recent earnings call.
Yet, this newest clinical hold has clearly shaken investors' optimism. Alnylam shares traded at $76.38 apiece by market's open on Thursday, down 11% from Wednesday's close.
Moving forward, the company plans to introduce amendments to fitusiran study protocols to improve patient safety. Notably, it is evaluating methods that would better allow investigators to prevent blood clots or identify when a patient is more at risk for them.
"I would certainly admit that across all clinical trial programs, not just hemophilia, I think we struggle to identify a definitive biomarker that we can rely on that's predictive of thrombotic potential," Steven Pipe of the C.S. Mott Children's Hospital at the University of Michigan said during a Sept. 7 Alnylam investor call, adding that the protein D-dimer is one important means to that end.
"There's lots of inhibitor studies where patients are getting more than one bypassing agent to treat bleeding, and d-dimers have been used as an early biomarker — or a warning, if you like — of when maybe you need to back off on dosing or the intensity of concomitant administration. So I think that is one tool that can be looked at," he said.
"The moral of the story always is in this context we want to be cautious about factor usage," Alnylam's head of R&D, Akshay Vaishnaw, added during the call.
Alnylam hopes to resume its fitusiran studies "as soon as possible," and maybe as soon as late 2017, according to a Sept. 7 statement.
In contrasting news, the company also reported Thursday positive interim results from a Phase 1 study of givosiran in patients with acute hepatic porphyrias.