LIB's cholesterol-busting drug aces 2nd phase 3 trial, keeping Amgen blockbuster in its sights

LIB Therapeutics has passed another milestone on its path to launching a challenger to cholesterol drugs sold by Amgen, Regeneron and Sanofi. In the latest phase 3 readout, the private biotech’s subcutaneous PCSK9 inhibitor cut levels of LDL cholesterol to maintain momentum going into its final two data drops.

Cincinnati-based LIB set up shop in 2015 to advance assets from Bristol Myers Squibb. Eight years later, the biotech, which has kept a low profile, has clinical data from two phase 3 PCSK9 trials and is on course to wrap up its two remaining late-stage studies in early November. The program is testing lerodalcibep, a small recombinant fusion protein of a PCSK9-binding domain, in a range of cardiovascular indications.

The latest clinical data, which LIB presented at the European Society of Cardiology and published in the European Heart Journal, cover the use of lerodalcibep in heterozygous familial hypercholesterolemia (HeFH) patients. HeFH is a genetic disorder that causes high cholesterol levels.

Investigators randomized 478 people who had high cholesterol, despite taking high-intensity statins and ezetimibe, to receive monthly subcutaneous doses of lerodalcibep or placebo. After six months, levels of LDL-C in the lerodalcibep arm had fallen by 58.6% compared to the placebo group. The mean decline in the final two weeks of the study was 65%.

In a European Cardiology Review video, lead investigator Derick Raal, Ph.D., a professor at the University of the Witwatersrand in South Africa, called the LDL-C reduction “remarkable.” Amgen’s PCSK9 drug Repatha achieved (PDF) a similar drop in LDL-C in a 12-week study, but lerodalcibep has potential advantages over the incumbent antibody and a rival drug, Praluent, from Regeneron and Sanofi.

“It's a much smaller protein, so it can be given in a smaller volume that's stable at room temperature, and it can be administered less frequently than monoclonal antibodies, which normally have to be administered every two weeks. This therapy is administered just once a month,” Raal said.

LIB now has phase 3 data on the use of lerodalcibep in patients with HeFH and homozygous familial hypercholesterolemia. The final two phase 3 clinical trials are assessing the drug candidate in more than 1,800 patients who have cardiovascular disease (CVD) or are at high and very high risk for CVD, and more moderate LDL-C elevations despite maximal tolerated statins and other oral therapy.

Lerodalcibep is part of a set of drug candidates designed to realize the promise of PCSK9 inhibition, a mechanism that reduces LDL-C but is yet to live up to early commercial forecasts. Merck & Co. is going after the same opportunity with the oral PCSK9 inhibitor it recently moved into phase 3.