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Crestor manages cholesterol elevation during NGM282 NASH therapy

Crestor safely and effectively managed NGM282-associated LDL cholesterol elevation, according to a study published in Journal of Hepatology.

“NGM282-associated elevation of cholesterol is mainly driven by an increase in the large, buoyant LDL particles, which are considered to be less atherogenic than the small, dense LDL particles,” Mary Rinella, MD, from Northwestern University in Chicago, and colleagues wrote. “Importantly, co-administration of [Crestor] in these patients reduced concentrations of total cholesterol, LDL-C and LDL particles to levels below baseline.”

The study comprised 66 patients who received 0.3 mg, 1 mg or 3 mg of NGM282 daily for up to 2 weeks. Patients then began concurrent therapy with daily 20 mg Crestor (rosuvastatin, AstraZeneca) whether statin naive or switching from concurrent statin therapy.

At week 2, LDL cholesterol was significantly elevated in the NGM282 0.3 mg group (27.6 mg/dL; P < .001), the 1 mg group (54.2 mg/dL; P < .001), and the 3 mg group (50.6 mg/dL; P < .001) compared with baseline.

LDL-C rapidly decreased after rosuvastatin initiation with changes of 43.2 mg/dL in the 0.3 mg group, 59.2 mg/dL in the 1 mg group, and 46.3 mg/dL in the 3 mg group by week 4. The decline of LDL-C continued through week 6 and week 12.

At week 12, 83% of patients in the NGM282 0.3 mg group, 76% in the 1 mg group, and 79% in the 3 mg group achieved LDL-C levels lower than baseline.

Additionally, triglyceride plasma concentrations declined steadily during the study in all three NGM282 groups. The relative changes in triglyceride levels at week 12 were 14% in the 0.3 mg group, 26% in the 1 mg group, and 34% in the 3 mg group compared with baseline.

“Future studies should also explore lower rosuvastatin doses, slower escalation and alternative lipid-lowering therapies for coadministration with NGM282,” Rinella and colleagues wrote. “Further understanding of the cardiovascular effects of NASH and insights into potential cardiovascular benefits of treating this chronic disease may have important implications on clinical practice.” – by Talitha Bennett

Disclosure: Rinella reports research or grant support from Novartis; advisory committee or review panel roles with AbbVie and Intercept; and has consulted for Enanta, Fibrogen, Gilead, Immuron, Intercept, Madrigal, NGM Biopharmaceuticals, Novartis, Pfizer and Taiwan J. Please see the full study for the other authors’ relevant financial disclosures.