Ionis slips as safety concerns offset efficacy in FCS phase 3

Ionis Pharmaceuticals saw its share price fall 8% after it posted results from a phase 3 trial of its antisense drug volanesorsen in patients with familial chylomicronemia syndrome (FCS). The trial further demonstrated volanesorsen cuts triglyceride levels and as such met its primary endpoint, but the safety data also stoked fears that declines in platelet counts could affect antisense therapies.

Akcea Therapeutics, a wholly owned subsidiary of Ionis, reported a 77% drop in triglycerides from baseline among the 33 patients who took volanesorsen for three months, easily beating the 18% rise seen in the placebo group. That was enough for the study to hit its primary endpoint. And with the drug also performing well against secondary endpoints and in a previous phase 3 trial, the drug looks well set from an efficacy perspective as it heads toward planned regulatory submissions.

Doubts about the drug stem from the safety data. Ionis saw its stock price slump and its partner GlaxoSmithKline scrap plans for a trial last year after FDA put a clinical hold on a study of another antisense drug, IONIS-TTRRx. The clinical hold related to cases of severe platelet deficiency, an issue that also appeared to affect some patients who received volanesorsen.

The latest phase 3 data drop adds to the link between volanesorsen and low platelets. Of the 33 patients treated with volanesorsen, five dropped out because of falling platelet levels. A further five patients discontinued treatment after suffering injection site reactions, resulting in the dropout rate in treatment arm topping 30%. None of the platelet level dropouts occurred after Ionis adopted a monitoring program, lending credence to its claims the issue is manageable.

Ionis thinks FCS, a rare condition that hinders the body’s ability to clear triglycerides, contributes to the platelet declines, making it more of a disease-specific concern than the class-wide problem feared by investors. That didn’t stop Wall Street from looking past the efficacy results—which were expected to be positive after the previous phase 3—and wiping 8% off Ionis’ $6 billion market cap in the wake of the latest data.

The next people Ionis has to convince of the merits of the data are regulators. Ionis CEO Stanley Crooke has spoken of a desire to get volanesorsen in front of regulators as soon as possible. And, with phase 3 data now in hand, the company is set to file submissions in the U.S., European Union and Canada this year.