Gemphire sparkles on third trial win for lead drug gemcabene

Trial investigator and Gemphire medical advisory board member Evan Stein M.D., Ph.D. (Gemphire)(Gemphire / Evan Stein)

Shares in Gemphire Therapeutics more than doubled after its lead drug gemcabene aced a midstage trial in patients with high triglycerides—setting up a phase 3 program.

The INDIGO-1 trial showed that gemcabene hit the target of reducing triglycerides in patients with severely elevated levels that raise the risk of developing serious cardiovascular complications, adding to two earlier wins in the rare lipid disorders homozygous and heterozygous familial hypercholesterolemia (HoFH/HeFH).

Analysts at Jefferies said the company is hoping to start the phase 3 program in severe hypertriglyceridemia (SHTG) next year and is also thinking about starting trials in the much larger mixed dyslipidemia patient population, which could make it a potential therapy for many millions of patients.

Added to that, Gemphire is also expecting data before the end of the year in familial partial lipodystrophy (FPL), a rare disease that could be a read-through for nonalcoholic steatohepatitis (NASH)—a hot area for drug development and another potentially lucrative market for the drug.

“The next step for a MD program is currently unclear as [Gemphire's] near-term goal is to move into phase 3 in SHTG,” note the analysts.

In INDIGO-1, triglyceride levels were cut 47% with a higher 600mg dose of gemcabene group, compared to a 27% reduction with placebo, and Gemphire said on a conference call that it would take that dose forward into phase 3. A lower 300mg dose reduced triglycerides by 33%. The reductions came even though around half of the patients were already being treated with cholesterol-lowering statin drugs.

Gemcabene also significantly reduced other biomarkers—including LDL-cholesterol and apolipoproteins B, E and CIII—linked to the development of atherosclerosis and inflammation. There was just one miss out of the secondary endpoints, with gemcabene showing only a trend toward improving C-reactive protein (CRP) which the biotech put down to the size of the trial.

The trial’s lead investigator Evan Stein M.D., Ph.D., of the Metabolic & Atherosclerosis Research Center in Cincinnati, said that around 70% of the 600mg arm achieved the treatment goal of driving triglyceride levels down below 500 mg/dL, which is important as it reduces the potential for pancreatitis.

The broad effects of the drug on biomarkers “were greater in the subgroups that are even more difficult to treat, those with diabetes and already on statins,” he pointed out.

Gemcabene “has the potential to address the “triple threat of cholesterol, triglycerides and inflammation in cardiometabolic disease, including SHTG, hypercholesteremia, and NASH,” according to Gemphire’s CEO Steven Gullans Ph.D., who took over the helm of the biotech after Mina Sooch resigned a year ago.

“There are approximately 3.5 million SHTG patients in the U.S. in need of lowering their triglyceride levels below 500 mg/dL to reduce their risk of developing acute pancreatitis,” he added.

The drug has also been shown to be safe and effective in combination with all current treatments for hypercholesterolemia, including high-intensity statins, injectable PCSK9-targeting antibodies (Amgen’s Repatha or Sanofi/Regeneron’s Praluent) and Merck & Co’s Zetia, according to Gemphire.

There’s another important data read-out for Gemphire in the coming months, as the FDA has asked for a rodent carcinogenicity study to rule out any activity against PPAR-alpha—a risk factor for cancer. That data is due in the third quarter, according to Jefferies, and will need to be in place ahead of the end-of-phase 2 discussions with the FDA.