Sanofi is preparing to seek an additional indication of Praluent (alirocumab), a proprotein convertase subtilisin/kexin type 9 (PCSK 9) inhibitor that lowers high cholesterol.
As the company confirmed the drug’s efficacy to reduce cardiovascular risks in the clinical trial ODYSSEY OUTCOMES, it will try to use the outcome as a basis for an additional indication, sources said.
Sanofi’s move is likely to gain faster momentum because the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recently adopted a favorable opinion for Praluent’s expansion of indication.
“The CHMP expressed a positive opinion to reflect Praluent’s efficacy in reducing cardiovascular risks on European approval. The European Commission is expected to make the final decision in the coming months,” Sanofi said.
Data from ODYSSEY OUTCOMES has also been submitted to the U.S. Food and Drug Administration, with a target action date of April 28, 2019, it added.
The drugmaker is hoping to obtain a new indication for Praluent in Korea, too.
If Sanofi wins additional indication for Praluent, the drug will be used as another treatment option, along with Amgen’s Repatha, to prevent recurrence of atherosclerotic cardiovascular disease (ASCVD) in adult patients.
If Repatha is used as an adjunct to correction of other risk factors in ASCVD patients, for lowering LDL-cholesterol and reducing cardiovascular risks, in addition to a maximally tolerated dose of statin or in addition to statin or other cholesterol-reducing therapy, Praluent is used in combination with maximally tolerated dose of statin or used alone in statin-intolerant patients.
The PCSK9 inhibitor drew attention with its strong LDL-cholesterol lowering effect and quickly solidified its status as a treatment for hypercholesterolemia.
In 2017, the American Society for Clinical Endocrinology (AACE) revised the dyslipidemia management guideline to include a PCSK 9 inhibitor as a new treatment option.
In late August in 2018 in Korea, the Korean Society of Lipid and Atherosclerosis (KSoLA) enhanced the therapeutic target and treatment standard for cardiovascular risks and included PCSK 9 inhibitors in the list of treatments for dyslipidemia in the latest guideline.
PCSK 9 inhibitor has become a treatment for hypercholesterolemia faster than expected, but it also has to overcome various issues as a second-line treatment.
The absence of long-term efficacy and safety profile and the uncertainty of cost-effectiveness are cited as the most significant hurdles to use PCSK 9 inhibitors in
Researchers are still working on whether PCSK 9 inhibitors significantly lower cardiovascular events and mortality consequently. Both the FOURIER study on Repatha and ODYSSEY OUTCOMES on Praluent were not fully enough to yield a meaningful result to prove the effectiveness of death reduction.
Praluent lowered the risk of major adverse cardiovascular events (MACE) by 15 percent, compared to placebo, in the ODYSSEY OUTCOMES study. In the high-risk patient group with LDL-C levels at 100mg/dL or more, the drug lowered MACE risk by 24 percent and all-cause mortality by 29 percent. However, it was not fully enough to prove its direct effectiveness in reducing mortality.
However, Sanofi said the median 2.8 years of follow-up was too short to demonstrate the effectiveness of reducing mortality. The company emphasized that the ODYSSEY OUTCOMES study was the first to show a correlation between a non-statin lipid-lowering drug and death reduction.
In Korea, PCSK 9 inhibitors are not covered by insurance, except for very rare Homozygous Familial Hypercholesterolemia (HoFH). Repatha is the only insurance-available HoFH indication.
If the Korean government approves Praluent’s new indication for reducing cardiovascular risks, Praluent will be able to compete against Repatha for high-risk patients with ASCVD.