Things were looking up for Gemphire Therapeutics in June, when its lead drug gemcabene sailed through a midstage hypertriglyceridemia trial. Now, the company is halting its phase 2a trial in pediatric nonalcoholic fatty liver disease (NAFLD) because some patients’ disease got worse.
The trial started early this year and dosed patients with 300 mg of gemcabene daily. Its primary endpoint was a change in serum alanine transaminase (ALT), an enzyme biomarker of liver function, after 12 weeks of treatment, while its secondary endpoints included a change in hepatic steatosis, the buildup of fat in the liver.
The first three patients that completed 12 weeks of treatment had an increase in liver fat content, as well as elevated ALT levels.
“The increase in liver fat was deemed an unexpected problem by the trial investigator because it was an unexpected consistent pattern of worsening of the disease, rather than improvement, creating risk to the patients, which the investigator believed was likely due to the drug,” Livonia, Michigan-based Gemphire said in a statement.
The data and safety monitoring board overseeing the trial recommended Gemphire terminate it and follow up with the patients to collect more safety data.
Gemphire CEO Steve Gullans, Ph.D., pointed to the 1,200 patients who had been treated with the ex-Pfizer asset with no drug-related serious adverse events.
"Gemcabene-related adverse events (AEs) in these adult subject trials were observed to be comparable to those seen with placebo treatment. We remain confident that gemcabene has the potential to be an effective therapy for a host of cardiometabolic patients and we intend to continue to develop gemcabene to address multiple indications,” he said.
Gemphire licensed gemcabene from Pfizer back in 2011. Under that agreement, Pfizer had the right to cancel the agreement if Gemphire did not “adequately” commercialize the drug by April 2021. Earlier this week, the pair reworked the deal, which, among other things, extends the deadline of gemcabene’s first sale to April 2024.
In addition to NAFLD and severe hypertriglyceridemia, gemcabene is being developed for homozygous and heterozygous familial hypercholesterolemia and atherosclerotic cardiovascular disease, also called coronary artery disease.