Akcea’ and Ionis’ Waylivra Meets Endpoints in Study in Patients with Familial Partial Lipodystrophy

Rare Daily Staff

Akcea Therapeutics and Ionis Pharmaceuticals reported that their experimental therapy Waylivra (volanesorsen) met its primary and secondary endpoints in a clinical study as a treatment for patients with familial partial lipodystrophy, a rare lipid disorder.

Familial partial lipodystrophy (FPL), is characterized by abnormal fat distribution across the body and a range of metabolic abnormalities, including severe insulin resistance, dyslipidemia and hypertriglyceridemia, hepatic steatosis and, in affected women, features of hyperandrogenism. People with FPL often present with polycystic ovarian syndrome or unusually insulin-resistant diabetes and are at increased risk of acute pancreatitis in addition to long-term, progressive consequences including premature cardiovascular disease and liver disease, resulting in cirrhosis. They are unable to store fat or triglycerides in normal fat stores, so excess triglycerides are stored in the liver and muscle and accumulate at high levels in the bloodstream.

Waylivra, developed using Ionis’ proprietary antisense technology, is designed to reduce the production of ApoC-III, a protein that regulates plasma triglycerides and may also affect other metabolic parameters.

The study showed Waylivra achieved a statistically significant reduction in triglyceride levels and the a statistically significant reduction in liver fat.

“We are encouraged by the substantial reduction in triglycerides and hepatic fat fraction achieved with Waylivra in patients with FPL and we will be reviewing the totality of the data internally and with experts in the field to determine the most appropriate next steps for this program,” said Louis O’Dea, chief medical officer at Akcea Therapeutics, an affiliate of Ionis.

The goal of the BROADEN study was to assess the effects of Waylivra on triglyceride levels and other metabolic parameters in people with FPL. The randomized, placebo-controlled, double-blind study included 40 adult patients with a clinical diagnosis of FPL plus hypertriglyceridemia and fatty liver.

Results from the study show a statistically significant mean reduction from baseline of 88 percent in triglyceride levels in Waylivra-treated patients at three months compared to 22 percent reduction in placebo-treated patients. Significant triglyceride lowering was maintained throughout the 12 months study period.

Results also show a statistically significant mean reduction from baseline of 51.9 percent in liver fat in Waylivra-treated patients at 12 months compared to a 1.5 percent increase in placebo-treated patients.

The most common adverse events observed in Waylivra-treated patients were mild or moderate in severity and included injection site reactions, nasopharyngitis, urinary tract infection, and reductions in platelet levels.  There were no serious or severe decreases in platelets.

Akcea and Ionis received marketing authorization in Europe for Waylivra in May 2019 as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate.


Photo: Louis O’Dea, chief medical officer at Akcea Therapeutics

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