Ionis spinout Akcea files for approval of volanesorsen

Akcea Therapeutics has filed for FDA approval of volanesorsen. The Ionis Pharmaceuticals spinout sees the filing positioning it to bring the treatment of familial chylomicronemia syndrome (FCS) to market in the U.S. next year.

Ionis teed up cardiovascular antisense drug volanesorsen for the NDA with data drops from phase 3 trials in December and March. Those studies showed volanesorsen lowers triglyceride levels in patients with severe hypertriglyceridemia and FCS, a rare condition that restricts clearance of the fats. The 77% fall in triglyceride levels in patients with FCS suggests volanesorsen is effective in this population.

That puts Akcea, which spun out of Ionis in July with a $125 million IPO, in a good position to convince the FDA of the efficacy of volanesorsen. The conversation about the safety of the drug could be trickier, though.

Investors have been hypersensitive to data linking volanesorsen and other antisense drugs to low platelet counts. The phase 3 data released in March sent Ionis’ stock down 8%, despite being a clear hit from an efficacy perspective. That reaction stemmed from news that five of the 33 patients in the trial dropped out because of falling platelet counts. Another five stopped treatment because of injection site reactions. That put the dropout rate in the volanesorsen arm at 30%.

Ionis and, since striking out on its own, Akcea have argued the platelet declines are tied to FCS, a disease associated with variable levels of the thrombocytes. And, that by adopting a monitoring program, the risk can be mitigated. None of the platelet-related dropouts happened after Ionis put a monitoring program in place. Akcea plans to apply the same model postapproval by providing platelet monitoring.

RELATED: Ionis slips as safety concerns offset efficacy in FCS phase 3

The ability of Akcea and healthcare sites to effectively implement this program may be questioned during the FDA review process. The regulator sent a warning letter to a study site trialing another Ionis’ drug, IONIS-TTRrx, in March for failing to comply with platelet monitoring requirements. The news wiped 6% off Ionis’ stock and prompted one analyst to cut his target price on the grounds the inability of a study site to comply boded badly for the real-world prospects of the program.

As with other news that has dented Ionis’ stock over the past year, there is a more benign reading of the warning letter. Notably, when the FDA visited the site in October and November they found fault with its records from May and June, shortly after the new monitoring program came into force. That suggests the site got the hang of the monitoring procedure after some early teething problems.