Nine clinical trials testing PCSK9-antibody meet primary efficacy endpoint

Nine new phase III trials testing alirocumab, a monoclonal antibody directed at PCSK9, in people with hypercholesterolaemia met their primary endpoint of a greater percent reduction from baseline in LDL-c at 24 weeks when compared with placebo or active comparator.

The trials are part of the ODYSSEY clinical trial program, which evaluates alirocumab in addition to standard-of-care lipid-lowering therapy, in patients with heterozygous familial hypercholesterolaemia (HeFH, trials ODYSSEY FH I, FH II and HIGH FH) or patients with high or very high cardiovascular (CV) risk (trials ODYSSEY COMBO I, COMBO II, OPTIONS I, OPTIONS II and LONG TERM). In the ODYSSEY ALTERNATIVE study, patients did not receive concomitant standard-of-care lipid-lowering therapy, due to a history of being intolerant to statins.
The trials evaluated two distinct dosing regimens: 150 milligrams (mg) every two weeks or 75 mg every two weeks increasing to 150 mg if needed to reach protocol-specified LDL-C targets. The 75 mg and the 150 mg dose were delivered with a single, self-administered one-milliliter (mL) injection.

Mean percent reduction in LDL-c from baseline at 24 weeks in alirocumab-treated patients in these nine ODYSSEY trials was consistent with results seen in previous alirocumab trials. Also in patients with a history of intolerance to two or more statins, patients randomised to alirocumab showed a greater percent reduction from baseline in LDL-c at week 24 compared to ezetimibe.

Alirocumab was generally well tolerated in the 9 ODYSSEY trials. The most common adverse events were nasopharyngitis and upper respiratory tract infections, which were generally balanced between treatment groups. Injection site reactions occurred more often in the alirocumab group compared to placebo. Serious adverse events and deaths were generally balanced between treatment groups as were other key adverse events including musculoskeletal, neurocognitive and liver-related events.

In the LONG TERM trial, a pre-specified interim safety analysis was performed when all patients reached one year and approximately 25 percent of patients reached 18 months of treatment.  A statistically significantly lower rate of adjudicated major CV events (cardiac death, myocardial infarction, stroke, and unstable angina requiring hospitalisation) was observed in the alirocumab arm compared to placebo in a post-hoc analysis. The potential of alirocumab to demonstrate CV benefit is being prospectively assessed in an ongoing 18,000-patient ODYSSEY OUTCOMES trial.

“Clinical data to date show consistent, positive results in LDL-C lowering, with an encouraging safety and tolerability profile across all Phase 3 alirocumab trials that we have reported,” said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President, Regeneron Laboratories. “Importantly, in the trials that used an individualized approach with 75 mg and 150 mg doses, the majority of patients reached their LDL-C goal while remaining on a 75 mg dose. This dosing approach was designed to provide physicians and patients with the flexibility to tailor therapy to patients’ lipid-lowering needs.”

The 9 ODYSSEY trials reported now, along with the previously announced MONO trial, encompass over 5,000 patients studied in double-blind trials for 24-104 weeks. More detailed data will be presented at upcoming medical congress.

Source: Press release Sanofi and Regeneron, 30 July 2014