FDA approves two unique nonstatin drugs that lower LDL-C
For the first time in nearly 2 decades, FDA has approved two new oral nonstatin drugs that lower LDL-C: bempedoic acid (Nexletol) and bempedoic acid and ezetimibe (Nexlizet), both manufactured by Esperion.
Indicated for adjunct use with diet and maximally tolerated statin therapy, the once-daily medications provide additional lowering of LDL-C in adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease.
Bempedoic acid, the first in a new class of drugs, lowers LDL-C by inhibiting cholesterol synthesis in the liver. Approval was based on the results of the global Phase III LDL-C lowering study of more than 3,000 patients. Administered with moderate- or high-intensity statins, the drug led to an average of 18% placebo-corrected decrease in LDL-C.
Bempedoic acid’s effect on cardiovascular morbidity and mortality has not been determined.
Bempedoic acid and ezetimibe—the first nonstatin, LDL-C lowering combination medication ever approved—lowers elevated LDL-C by inhibiting cholesterol synthesis in the liver and absorption in the intestine.
Approval was supported by the Phase III Fixed Combination Drug Product LDL-C lowering program, as well as safety data from the Phase III bempedoic acid trial and the existing ezetimibe safety profile. When added on to maximally tolerated statins, the combo drug lowered LDL-C by 38% percent compared with placebo.
Label warnings and precautions include hyperuricemia, with the development of gout in a small percentage of patients, as well as increased risk of tendon rupture or injury. In clinical trials, adverse events reported most frequently were upper respiratory tract infections, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes. The majority were mild to moderate in severity.
Additional adverse events reported for bempedoic acid and ezetimibe were diarrhea, arthralgia, sinusitis fatigue, and influenza.
Bempedoic acid will be available by prescription on March 30, 2020, and bempedoic acid and ezetimibe will be available in July 2020. Both drugs are expected to cost about $10 per fill for up to a 3-month supply, according to Esperion.