"Familial chylomicronemia syndrome is a rare and very serious genetic disorder that is estimated to affect 3,000 to 5,000 patients worldwide. FCS patients are characterized by their extremely high levels of triglycerides, often higher than 2,000 mg/dL. These patients accumulate chylomicrons, which are derived from dietary intake and are the largest of the triglyceride-rich particles. FCS patients are difficult to treat because, due to their genetic defect, they are unable to clear triglyceride particles which build up in their blood. As such, a drug is needed that can help effectively clear chylomicrons from the blood, thereby reducing triglyceride levels in these patients," said
The Phase 2 open-label cohort was designed to assess the safety and activity of ISIS-APOCIIIRx in patients with extremely high triglyceride levels and a genetic confirmation of FCS. The data reported today are the final data from three FCS patients who all had baseline triglyceride levels greater than 1,400 mg/dL and completed 13 weeks of treatment with 300 mg of ISIS-APOCIIIRx. Isis reported an interim analysis of these data in September 2013. In this study, all three patients treated with ISIS-APOCIIIRx achieved substantial reductions in total triglyceride levels with a mean reduction of 69 percent that correlated with a comparable reduction of 69 percent in chylomicron-triglycerides. In addition, these patients experienced positive effects on other lipid parameters, including a mean reduction of 81 percent in apoC-III, a mean reduction of 81 percent in apoC-III-associated VLDL-C, and a mean increase of 78 percent in HDL-C. Because FCS is an extremely rare genetic disorder affecting one to two people per million, clinical trials in this disease are generally quite small.
ISIS-APOCIIIRx was well tolerated in the study. The most common adverse event was injection site reactions, which were predominantly mild and typically resolved rapidly. There were no flu-like symptoms, no treatment-related elevations of liver enzymes greater than three times upper limit of normal, no abnormalities in renal function, no clinically meaningful changes in other laboratory values and no treatment-related serious adverse events.
"Our initial focus is to bring ISIS-APOCIIIRx to the market for patients with FCS. These are patients who cannot reduce their triglycerides to safe levels with currently available medicines. We are extremely pleased with the performance of ISIS-APOCIIIRx to date. We believe that the significant unmet medical need for an effective triglyceride-lowering drug for patients with FCS and the robust, consistent effects we observe with ISIS-APOCIIIRx should enable us to rapidly move forward," said
FCS is a rare genetic disorder that affects approximately one to two out of a million people. The most common genetic cause of FCS is a defect in the lipoprotein lipase (LPL) gene, which results in extremely low levels of LPL activity and a significant reduction in the breakdown of triglycerides from the blood. In the study reported today, all three patients were homozygotes for null LPL gene mutations resulting in undetectable LPL activity.
ISIS-APOCIIIRx is an antisense drug intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents. ISIS-APOCIIIRx targets apoC-III, a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Humans who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease. Humans with elevated levels of apoC-III have high triglycerides associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome. In addition, the prevalence of type 2 diabetes is increased in patients with elevated triglycerides. Humans with elevated levels of triglycerides are at risk of many serious health conditions, including pancreatitis, which can be life-threatening and require hospitalization.
Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners. Isis' broad pipeline consists of 32 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders, and cancer. Isis' partner, Genzyme, is commercializing Isis' lead product, KYNAMRO®, in
This press release includes forward-looking statements regarding the discovery, development, and potential of drugs for cardiovascular diseases, and the development, activity, therapeutic potential and safety of ISIS-APOCIIIRx. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended
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D. Wade Walke, Ph.D., Vice President, Corporate Communications and Investor Relations, 760-603-2741; Amy Blackley, Ph.D., Associate Director, Corporate Communications, 760-603-2772