Volanesorsen reduces pancreatitis, triglycerides in familial chylomicronemia

LAS VEGAS — Volanesorsen reduced triglycerides and the incidence of pancreatitis in patients with familial chylomicronemia syndrome, according to data presented at the National Lipid Association Scientific Sessions.

Andres Gelrud, MD, director of the pancreatic disease program at the Miami Cancer Institute, and colleagues analyzed data from the APPROACH and COMPASS trials.

As Cardiology Today previously reported, the COMPASS trial found that patients with hypertriglyceridemia treated with the investigational drug volanesorsen (Akcea Therapeutics) experienced a decrease in their triglyceride levels.

In the APPROACH trial, patients with familial chylomicronemia syndrome were assigned subcutaneous volanesorsen (n = 33; mean age, 47 years; 49% men) or placebo (n = 33; mean age, 46 years; 42% men). Patients with hypertriglyceridemia were also treated with subcutaneous volanesorsen (n = 75; mean age, 50 years; 25% men) or placebo (n = 38; mean age, 53 years; 21% men) in the COMPASS trial.

Patients in the APPROACH trial were treated with 52 weekly injections, whereas patients in the COMPASS trial received 26 weekly injections.

The primary endpoint was the effect of volanesorsen on the reduction of triglycerides at 3 months. The secondary endpoint was the effect of volanesorsen on abdominal pain intensity.

Volanesorsen reduced triglycerides by 77% in the APPROACH trial and 71% in the COMPASS trial compared with placebo (+18% and –1%, respectively). This treatment also decreased the number of events related to pancreatitis vs. placebo when data from the COMPASS and APPROACH trials were combined (6 events vs. 1 event; P = .019).

Patients at high risk for recurrent attacks had decreased risk with volanesorsen vs. placebo (4 events vs. 0 events; P = .02).

In the APPROACH trial, the average maximum pain intensity decreased in patients assigned volanesorsen compared with placebo.

The most common adverse events were mild and related to local cutaneous injection-site reactions in the APPROACH and COMPASS trials (17% and 39%, respectively). No major bleeding events, cardiac toxicity or renal or hepatic safety signals were seen in patients from both trials.

“When the target is approved, it will make a benefit in the lives of the patients because these patients do see a significant burden of disease because of the high triglycerides and the constant pancreatitis, hospitalizations that they have to undergo,” Swati Thorat, senior manager of medical communications at Akcea Therapeutics, told Cardiology Today. “We still have a long way to go before we can get it to patients, but we have all the data on safety and tolerability of the drug.” – by Darlene Dobkowski

Reference:

Gelrud A, et al. Treatment with volanesorsen reduced triglycerides and pancreatitis in patients with familial chylomicronemia syndrome and severe hypertriglyceridemia vs. placebo: Results of the APPROACH and COMPASS studies. Presented at: National Lipid Association Scientific Sessions; April 26-29, 2018; Las Vegas.

Disclosures: The APPROACH and COMPASS studies were funded by Ionis Pharmaceuticals/Akcea Therapeutics. Gelrud reports he received consultant honoraria and/or speaker fees from AbbVie, Akcea Therapeutics and Boston Scientific, a research grant from Dompe and royalties from UpToDate. Thorat is an employee of Akcea Therapeutics.