Ionis’ volanesorsen hits efficacy endpoint in phase 3

Ionis Pharmaceuticals' corporate headquarters in Carlsbad, CA

Ionis Pharmaceuticals has reported positive efficacy data from a phase 3 trial of volanesorsen in patients with severe hypertriglyceridemia. The antisense drug bested placebo in terms of reducing triglycerides, resulting in the study hitting its primary endpoint.

Investigators enrolled 113 patients in the trial and randomized them to receive either volanesorsen or a placebo. Triglyceride levels among the 75 subjects in the treatment arm fell 71.2% over the first 13 weeks of the study, compared to a drop of 0.9% in the placebo cohort. The effect of the drug on triglycerides persisted throughout the duration of the 26-week study, according to Ionis.

The 13-week change in triglyceride levels was enough for the study to meet its primary endpoint. And Ionis gathered other data to suggest the effect of volanesorsen is clinically meaningful. After 13 weeks of treatment, 82% of patients in the volanesorsen arm had triglyceride levels of 500 mg/dl or less. Only 14% of subjects in the placebo cohort hit this level.

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Ionis is particularly interested in a subset of patients with familial chylomicronemia syndrome (FCS), a rare hereditary condition that causes high levels of triglycerides. Going into the trial, the seven FCS patients had triglyceride levels of 2,280 mg/dl on average. After 13 weeks of treatment, triglyceride levels in three of the five FCS patients who received volanesorsen had fallen to 500 mg/dl or less. Overall, triglyceride levels among FCS patients in the volanesorsen arm fell 73%, compared to a 70% increase in the two-patient placebo arm.

That performance offers Ionis cause for encouragement as the clinical development program enters a critical period. Data from a study in FCS patients are due in the first quarter of next year. And, if all goes to plan, Ionis will show volanesorsen can make a meaningful difference to patients with the syndrome.

“People with FCS have particular challenges because in addition to having triglyceride levels that can be 10 to 20 times normal values, the currently available triglyceride-lowering drugs are usually ineffective,” Université de Montréal’s Dr. Daniel Gaudet said in a statement. “The data from studies in patients with FCS treated with volanesorsen, including those from the COMPASS study, show that for the first time these patients can achieve the triglyceride reductions needed to potentially improve their health.”

The upbeat reading of the data failed to drive up Ionis’ share price, potentially in part because of concerns a more detailed breakdown of the results will render the findings less impressive. Notably, Ionis is yet to provide a close look at the safety data, an area in which volanesorsen could be vulnerable.

Shares in the RNA-targeted R&D shop plunged 40% in May after investors were hit with a double whammy. First, GlaxoSmithKline canned a trial of IONIS-TTRRx over safety concerns. Then, Ionis said similar issues related to declines in platelets may affect volanesorsen.

In the volanesorsen phase 3 release, Ionis said “there were no serious platelet events in the study” without providing further details to allay concerns.