- Briefing documents released ahead of a May 10 advisory panel meeting are confirming investor fears that safety signals may block Ionis Pharmaceuticals and Akcea Therapeutics' volanesorsen from market, or at least seriously impair the drug if it gets there.
- The chief concern is the reduction in blood platelet counts seen among patients treated with the antisense oligonucleotide (ASO). Representatives from the Food and Drug Administration noted in their briefing documents that mild platelet reduction is common with ASO therapy, but significant portions of patients treated with volanesorsen experienced steep drops.
- "At present, we have no evidence that the risk of severe thrombocytopenia diminishes with time," the agency representatives wrote, suggesting too that a risk evaluation and mitigation strategy (REMS) for volanesorsen be put in place should the drug gain approval.
Investor optimism in volanesorsen really started to waver earlier this year, when data came out from a pivotal safety and efficacy study that tested it in patients with a rare metabolic disorder called familial chylomicronemia syndrome (FCS).
The drug clearly worked, as those in the experimental arm had on average a 77% reduction in plasma triglyceride levels from baseline. But safety was an issue, particularly with thrombocytopenia. Two serious cases arose, though they resolved after patients discontinued treatment. More than half of patients taking volanesorsen experienced platelet reductions that dipped below 100,000/uL, versus none in the placebo group.
It looks as though those results are top of mind with the FDA representatives, as well as the advisory panel. One of the most extensive discussions the panel plans on having is about volanesorsen's associated risk of thrombocytopenia. A debate on whether a REMS program will be necessary is also on the docket.
That doesn't bode well for the drug, according to analysts.
"At this point, our confidence in this program and the platform overall (in addition to its competitiveness vs [Alnylam's] RNAi for intrathecal delivery) is dampened to a point that, along with our concerns about the broad commercial strategy, we are no longer about to recommend shares," EvercoreISI analyst Joshua Schimmer wrote in a May 8 note, downgrading Ionis shares from "Outperform" to "In-Line."
Ionis and Akcea have indicated they can wade through the regulatory headwinds. The companies spent much of their respective first quarter earnings calls discussing the launch preparations for volanesorsen and their hereditary ATTR treatment inotersen. The expected branded names for the drugs are Waylivra and Tegsedi, respectively.
"[T]he expanded access programs for Tegsedi and Waylivra are well underway, and patients are enrolling rapidly. In response to the enthusiasm from physicians and patients, we continue to expand the number of sites in the expanded access program," Sarah Boyce, president of Akcea, said on Ionis' earnings call.
Shareholders aren't as confident. Akcea stock fell more than 11% Tuesday morning to trade at $19.25 per share at market's open. Similarly, Ionis shares tumbled 10% to $39.77 apiece. They now are down about 19% year to date. Akcea is majority-owned by Ionis.