The supplemental BLA seeks FDA approval for alirocumab (Praulent) as a treatment to reduce overall risk of major adverse cardiovascular events.
The US Food and Drug Administration has accepted a supplemental Biologics License Application (sBLA) for alirocumab (Praluent Injection), a PCSK9 inhibitor. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of April 28, 2019.
The sBLA proposes an update to the Prescribing Information to include alirocumab as a treatment to reduce overall risk of major adverse cardiovascular events (MACE), which includes heart attack, ischemic stroke, death from coronary heart disease, and unstable angina requiring hospitalization.
The application included data from ODYSSEY OUTCOMES, a placebo-controlled phase 3 trial of 18,924 patients who had acute coronary syndrome in the 1-12 months (median 2.6 months) before trial enrollment.
The trial results showed an absolute risk reduction (ARR) of 1.6% (hazard ratio [HR], 0.85; 95% CI, 0.78—0.93; P = .0003) in MACE over the course of the 4-year study period.
Looking at patients with acute coronary syndrome and low-density lipoprotein cholesterol (LDL-C) levels at 100 mg/dL or greater, the study found that alirocumab reduced major adverse cardiovascular events by 24% with an absolute risk reduction of 3.4%.
As a PCSK9 inhibitor, alirocumab inhibits the binding of proprotein convertase subtilisin/kexin type 9 to the LDL receptor, which allows LDL receptors on surface liver cells to clear LDL and lower LDL-C levels in the blood.
Further data from the ODYSSEY OUTCOMES trial showed that among patients with diabetes, treatment with statins and alirocumab lowered risk of major adverse cardiovascular events by 2.3% (hazard ratio [HR], 0.84; 95% CI, 0.74 to 0.97).
For comparison, the absolute risk reduction for patients with prediabetes was 1.2% (HR, 0.86; 95% CI, 0.74 to 1.00) and the ARR for patients with normal glucose levels was 1.2% (HR, 0.85; 95% CI, 0.70 to 1.03).
"The analyses show adding alirocumab to maximally tolerated statins reduced the overall incidence of MACE, and the absolute risk reduction was highest among those with diabetes when compared to people with prediabetes or people without diabetes," said Kausik Ray, MD, ChB, a professor of public health at the School of Public Health of Imperial College in London, in a statement at the time the data was presented at the American Diabetes Association's 78th Scientific Sessions in June 2018.
Praulent is currently approved by the FDA as an injection indicated as a supplement to diet and statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol.
The most common adverse reactions (occurring in ≥5% of patients treated with alirocumab and occurring more frequently than with placebo) are nasopharyngitis, injection site reactions, and influenza, according to the current alirocumab Prescribing Information.