A cardiovascular drug Pfizer licensed from Akcea Therapeutics in 2019 hit the mark in a Phase IIb dose-ranging study in patients with elevated non-HDL-C and triglycerides.
Dan Kitwood/Getty Images
A cardiovascular drug Pfizer licensed from Akcea Therapeutics in 2019 hit the mark in a Phase IIb dose-ranging study in patients with elevated non-HDL-C and triglycerides.
Vupanorsen is an investigational antisense therapy that is being developed for cardiovascular risk reduction and severe hypertriglyceridemia, an abnormal triglyceride concentration in the blood.
This morning, Ionis Pharmaceuticals, which acquired Akcea last year, announced that the dose-ranging Phase IIb study met the primary endpoint. According to the announcement, patients who were treated with vupanorsen achieved a statistically significant reduction in non-HDL-C at all doses tested at 24 weeks compared to placebo.
Additionally, Ionis announced that patients who received the experimental medication achieved statistically significant reductions in triglycerides and angiopoietin-like 3 (ANGPTL3) at all dose levels at 24 weeks compared to placebo.
Vupanorsen is designed to reduce the production of ANGPTL3, a key regulator of triglyceride and cholesterol metabolism that occurs in the liver.
Pfizer licensed vupanorsen in October 2019 with a $250 million upfront payment. At the time Pfizer struck the licensing deal, Mikael Dolsten, chief scientific officer and president of Worldwide Research & Development and Medical at Pfizer, said the asset will complement the company’s clinical mid-stage internal medicine pipeline. The pharma giant took over the development of vupanorsen following positive Phase II data for hypertriglyceridemia that was reported by Akcea.
The Phase IIb study TaRgeting ANGPTL3 with an aNtiSense oLigonucleotide in AdulTs with dyslipidEmia (TRANSLATE-TIMI 70) included 286 patients ages 40 and older who have dyslipidemia. Patients received a range of dose levels over a period of 24 weeks. The primary endpoint was a percent change from baseline in non-HDL-C at week 24.
Sotirios “Sam” Tsimikas, vice president of global cardiovascular development and cardiovascular franchise lead at Ionis, expressed his excitement at the topline results of the Phase IIb study. He said the companies were pleased to see statistically significant reductions in non-HDL-cholesterol, which was the primary endpoint, as well as achieving the secondary endpoint of reductions of triglycerides at all doses tested.
“The topline results of the Phase IIb study also showed that vupanorsen dose-dependently lowered its target, angiopoietin-like 3. Pfizer is continuing to review the findings to determine next steps regarding future development,” Tsimikas said in a statement. He added that the company is looking forward to seeing the full data set from the study that will be presented at a medical conference in 2022.
The most common adverse events recorded were injection site reactions. Those most often happened in the highest vupanorsen dose group. The most common laboratory abnormalities reported were increases in liver enzymes, alanine aminotransferase and aspartate aminotransferase. Those were also primarily seen at the higher doses with no severe adverse events associated to the treatment.
