Isis Pharmaceuticals Reports Positive Clinical Data From Lp(a) Lowering Drugs

(RTTNews) - Isis Pharmaceuticals Inc. (ISIS), and its subsidiary, Akcea Therapeutics announced positive results from a Phase 2 study of ISIS-APO(a)Rx in which patients with high lipoprotein(a), or Lp(a), achieved reductions in Lp(a) of up to 94 percent, with a mean reduction of 71 percent.

Lp(a) is a known driver of cardiovascular disease. They also announced results from a Phase 1/2a study of ISIS-APO(a)-LRx in which subjects with elevated Lp(a) achieved dose-dependent reductions in Lp(a) of up to 99 percent.

ISIS-APO(a)-LRx is a LIgand Conjugated Antisense or LICA version of ISIS-APO(a)Rx. ISIS-APO(a)-LRx demonstrated a greater than 30-fold increase in potency in humans as compared to ISIS-APO(a)Rx.

In the Phase 2 study, patients with high or very high Lp(a) treated with ISIS-APO(a)Rx achieved substantial reductions in Lp(a) of up to 94 percent with a mean reduction of 71 percent (p = 0.001). In this study, patients treated with ISIS-APO(a)Rx achieved equal reductions of Lp(a) regardless of incoming Lp(a) levels. The Phase 2 study was a randomized, double-blind, placebo-controlled, dose-titration 12 week study evaluating ISIS-APO(a)Rx in 65 patients with Lp(a) levels that were high (greater than or equal to 50 mg/dL and less than 175 mg/dL) or very high (greater than or equal to 175 mg/dL). In this study, treatment with ISIS-APO(a)Rx was generally well tolerated with no safety issues observed.

In the Phase 1/2a study, subjects who received a single, low volume, subcutaneous injection of 10 mg, 20 mg, 40 mg or 80 mg of ISIS-APO(a)-LRx achieved robust, dose-dependent and durable reductions of Lp(a). Subjects who received a single dose of 80 mg ISIS-APO(a)-LRx achieved substantial reductions in Lp(a) of up to 97 percent and a mean reduction of 79 percent (p = 0.01) at 30 days. The long duration of effect resulted in significant Lp(a) reductions of nearly 50 percent at 90 days after the single dose.

Subjects who received multiple doses of 10 mg, 20 mg or 40 mg of ISIS-APO(a)-LRx achieved dose-dependent, significant reductions in Lp(a) of up to 99 percent, and a mean reduction of up to 92 percent (p =0.001). In this study, subjects treated with ISIS-APO(a)-LRx achieved similar reductions of Lp(a) regardless of incoming Lp(a) levels. The safety and tolerability profile of ISIS-APO(a)-LRx to date supports continued development: out of 159 injections there were no injection site reactions or flu-like symptoms reported.