Otsuka Pharmaceutical has submitted a New Drug Application (NDA) to the Japanese Ministry of Health, Labour and Welfare for bempedoic acid, a treatment for hypercholesterolemia and familial hypercholesterolemia. The application is based on positive Phase 3 trial results demonstrating the drug's efficacy and safety in Japanese patients.
The U.S. biopharma, Esperion Therapeutics, is behind the drug and "pushing for accelerated adoption and expansion into additional territories," according to an H.C. Wainwright & Co. report. Esperion retains commercial rights in the United States.
Phase 3 Trial Results
The Japanese Phase 3 trial, a placebo-controlled, randomized, multicenter, double-blind study, involved 96 patients with high LDL cholesterol who were either statin-intolerant or had an inadequate response to statins. Participants received either 180 mg of bempedoic acid or a placebo orally once daily for 12 weeks.
Preliminary results showed that bempedoic acid significantly reduced LDL-C levels by 25.25% compared to a 3.46% reduction in the placebo group (p<0.001). The safety and tolerability profile of bempedoic acid were consistent with previous trials, and no serious adverse events were observed.
Clinical Implications
Hypercholesterolemia affects a significant portion of the population, and many patients struggle to achieve target LDL-C levels despite statin therapy. Bempedoic acid offers a novel mechanism of action, inhibiting cholesterol synthesis in the liver by acting on ATP citrate lyase. This provides a new treatment option for patients who cannot tolerate statins or do not achieve sufficient LDL-C reduction with statins alone.
Further Expansion
Otsuka acquired exclusive rights to develop and commercialize bempedoic acid in Japan from Esperion in 2020 and is currently developing it domestically.
Esperion is also seeking regulatory approvals for bempedoic acid in Taiwan (marketed as Nilemdo) and Canada, with potential partnerships in Australia and Israel. H.C. Wainwright maintained a Buy rating on Esperion, with a price target of US$16 per share, implying a potential return on investment of 523%.
Cardiovascular Benefits
Exploratory data presented at the American Heart Association annual meeting in 2024 indicated that bempedoic acid (Nexletol and Nexlizet) provides additional cardiovascular benefits. The drug reduced major adverse limb events in patients with pre-existing peripheral artery disease by 36% compared to placebo. Bempedoic acid also significantly lowered the incidence of major adverse cardiovascular events in patients with liver steatosis or liver fibrosis.
Long-Term Data
Long-term follow-up data from the MILOS trial in Germany showed that Nilemdo (bempedoic acid) and Nustendi (bempedoic acid plus ezetimibe) lowered LDL-C cholesterol by an average of 30.3% after one to two years of treatment. The percentage of patients meeting their LDL-C goals increased sevenfold to 35.3% from 4.9% at baseline.
