Genzyme and Isis Pharmaceuticals Inc. announced that new two-year data from a phase 3 long-term extension study of KYNAMRO ® (mipomersen sodium) injection was presented at a scientific session at the annual American Heart Association meeting in Chicago, IL. In the study, a retrospective analysis showed that patients treated with KYNAMRO for a mean of two years had a significant reduction in Major Adverse Cardiovascular Events (MACE) compared to two years prior to therapy. This retrospective analysis included 104 patients who enrolled in the long-term extension study of KYNAMRO after having completed one of the KYNAMRO phase 3 blinded, randomized, placebo-controlled 6-month trials in patients with homozygous and heterozygous FH.

All patients who completed at least two years of treatment with KYNAMRO were included in the analysis. The rate of MACE in patients treated with KYNAMRO for two years were adjudicated by an independent committee and compared to the rate of MACE in the same patients based on their medical history prior to treatment with KYNAMRO. In this analysis, MACE were identified in 62% of patients during two years prior to KYNAMRO treatment, and 9% of patients during a mean of 24.4 months after initiation of treatment with KYNAMRO.

MACE were defined as myocardial infarction (MI), stroke, unstable angina (UA) and revascularization procedures (PCI/CABG). The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined.

Because of the risk of hepatotoxicity, KYNAMRO is available only through a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS. The goals of the KYNAMRO REMS are: to educate prescribers about the risk of hepatotoxicity associated with the use of KYNAMRO, and the need to monitor patients during treatment with KYNAMRO as per product labeling. To restrict access to therapy with KYNAMRO to patients with a clinical or laboratory diagnosis consistent with homozygous familial hypercholesterolemia (HoFH). KYNAMRO can cause elevations in transaminases.

In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) =3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT). KYNAMRO also increases hepatic fat, with or without concomitant increases in transaminases.

In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis. Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended.

During treatment, withhold the dose of KYNAMRO if the ALT or AST are =3x ULN. Discontinue KYNAMRO for clinically significant liver toxicity. Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS.