Rare Disease Report

Isis Begins Phase 3 Study in Patients with Familial Chylomicronemia Syndrome

SEPTEMBER 02, 2014
james Radke

Isis Pharmaceuticals, Inc. announced they have begun a phase 3 clinical trial evaluating the efficacy and safety of ISIS-APOCIIIRx in patients with familial chylomicronemia syndrome (FCS). 

FCS is a very rare genetic condition in which individuals lack properly functioning lipoprotein lipase (LPL), an enzyme that clears triglycerides from plasma. This disruption leads to very high concentrations of triglycerides and chylomicrons in the plasma (chylomicronemia).

The Phase 3 trial is a randomized, double-blind, placebo-controlled, 6 month study in which approximately 50 patients diagnosed with FCS will receive a weekly dose of ISIS-APOCIIIRx (300 mg) or placebo. The primary endpoint of the study is percent change in fasting triglycerides from baseline after three months of dosing.

“Current treatment options do not reduce triglyceride levels enough to reduce the risk of serious illness in patients with FCS."

In a statement, Sotirios Tsimikas, M.D., professor of medicine and director of vascular medicine at the University of California, San Diego and vice president of clinical development and leader of the cardiovascular franchise at Isis Pharma said, "FCS is a rare and very serious genetic disorder that is often associated with triglyceride levels higher than 2,000 mg/dL.  Because of their extremely high triglyceride levels, FCS patients are at significant risk of many serious health conditions, including frequent episodes of pancreatitis, which can require hospitalization and can be life-threatening. 
Current treatment options do not reduce triglyceride levels enough to reduce the risk of serious illness in patients with FCS."

Dr Tsimikas added, "ISIS-APOCIIIRx provides a unique therapeutic approach in that it is designed to reduce triglyceride levels by reducing apoC-III, an important regulator of triglyceride clearance.
The Phase 2 data strongly support advancing ISIS-APOCIIIRx into Phase 3 studies in patients with severely elevated triglycerides like FCS."

The phase 2 studies Dr Tsimikas referred to showed that FCS patients treated with ISIS-APOCIIIRx experienced significant decreases in triglyceride levels (i.e.,  1,500 mg/dL or more decrease).  In other phase 2 studies, patients with very high to extremely high triglyceride levels, who received ISIS-APOCIIIRx achieved substantial lowering of triglycerides (mean percent reductions of up to 71%) and apoC-III (mean percent reductions of up to 88%) and increasing of HDL-cholesterol (mean percent increases of up to 78%). This latter study involved patients with extremely high triglyceride levels but not necessary those with FCS who have severely high triglyceride levels due lack of a properly functioning LDLase.  In that regard, ISIS-APOCIIIR is being developed to treat patients with severely elevated triglycerides (i.e., >880 mg/dL) in addition to patients with FCS. Isis plans to initiate the Phase 3 program in patients with severely elevated triglycerides in 2014, in addition to the phase 3 study in patients with FCS.   

Going it Alone

Isis is no stranger to developing drugs for patients with rare lipidemias.  They developed the orphan approved drug Kynamro to treat homozygous familial hypercholesterolemia (HoFH) that is currently being marketed by their partner Genzyme. Unlike Kynamro however, Isis plans to advance ISIS-APOCIIIR on its own.  Richard Geary, Ph.D., senior vice president of development at Isis said. "Our broad experience developing drugs to treat lipid disorders, including the good working relationships we have established with the physicians and centers that treat many FCS patients should support the rapid advancement of this program.  We currently plan to advance ISIS-APOCIIIRx without seeking a partner." 

 “We currently plan to advance ISIS-APOCIIIRx without seeking a partner." 

ISIS-APOCIIIRx is an antisense drug designed to target apoC-III, a protein produced in the liver that plays a central role in the regulation of serum triglycerides.
For more information about ISIS-APOCIIIRx, visit http://www.isispharm.com/Pipeline/
For more information about FCS, visit http://fcs.raredr.com/

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