Researchers from the University of Pennsylvania presented preliminary data from a trial evaluating Regeneron Pharmaceutical‘s (NSDQ:REGN) injectable biologic drug therapy for reducing triglyceride levels. The team, led by Dr. Richard Dunbar, presented their work at the annual meeting of the American Heart Assn.
The Phase I, placebo-controlled, double-blind study tested the safety and efficacy of Evinacumab, an investigational monoclonal antibody specifically engineered to inhibit a protein which enables high triglycerides. The study enrolled 41 participants and monitored them for at least 5 months following the injection.
Researchers examined 6 dose levels and in the top 3 dose groups, triglycerides were lowered by 64% to 73%. The biologic was also well tolerated, with some participants reporting mild headaches.
“In this study, we tested a new approach for lowering triglycerides using an injectable drug that inhibits a specific protein which enables high triglycerides – Angiopoietin-like 3 (ANGPTL3). As expected, suppressing AngPTL3 resulted in a profound drop in triglyceride levels, as compared to a placebo,” Dunbar said in prepared remarks. “Encouragingly, the kinds of drops we saw appear to push beyond the boundaries of what is usually experienced with current oral medications.”
“Current medications such as fibrates or prescription fish oils effectively lower triglycerides, but leave much to be desired, each only lowering levels by 20 to 50 percent,” Dunbar said. “Validating a drug that lowers triglycerides well beyond that range would undoubtedly take us to the next level, particularly since it could be combined with current oral medications for those patients with extraordinarily high triglycerides who often can’t achieve safe levels with our usual medications. A similar approach has been taken for lowering certain cholesterol with the advent of PCSK9 inhibitors, which utilize a similar monoclonal antibody mechanism.”
The Pennsylvania team also noted dose-dependent reductions in cholesterol, including cholesterol from low-density lipoproteins (LDL). It is widely believed that LDL contribute to plaque buildup and the narrowing of arteries in the heart. The biologic also lowered cholesterol from high-density lipoproteins (HDL), which proved consistent with the drug’s mechanism targeting the AngPTL3 protein.
“Though the preliminary results give us a lot of hope that we could significantly improve triglyceride management, there is still a lot of work to be done to validate this approach,” Dunbar explained. “If all goes well and if this therapy makes it into clinical practice, the implications of this research are twofold. In the short term, profoundly lowering triglycerides may render hospital admissions less frequent in patients prone to pancreatitis, while long term, lowering triglycerides and associated cholesterol could also help reduce the risk of certain heart disease.”
The study was funded by Regeneron and the Tarrytown, N.Y.-based company provided the biologic for evaluation.