- Gemphire Therapeutics Inc. stock plummeted Monday morning after the company disclosed topline data for its sole pipeline candidate that, while positive, was hampered by a strong placebo response.
- In the ROYAL-1 Phase 2b study, patients on a 600 mg daily regimen of Gemphire's gemcabene demonstrated significantly lower LDL-cholesterol levels from baseline, with average reductions of 17.2% after 12 weeks of treatment. Despite meeting the study's primary endpoint, gemcabene's efficacy was diluted by the control group, which collectively had a 5.5% decline in the bad fats.
- "We powered the study for 17% reduction," Gemphire's Chief Medical Officer Lee Golden said during an Aug. 7 investor call. "When we looked at the data, the placebo was maybe a little bit better of an effect than what we had anticipated. Generally you see a few percent one way or another of zero — we were at five and a half percent in this study, so maybe a drop higher than we would have expected."
While ROYAL-1's placebo response may have been "a drop higher" than Gemphire had prepared for, it was clearly enough to rattle investor confidence. The company's shares fell 40% to $11.20 apiece by market's open on Monday, and continued to shrink down to $9.05 apiece later in the morning.
One potential source for the high placebo response could be the study's 12-week timetable, because longer investigations are often less affected by control group outcomes, the company reasoned.
"Generally, placebo over time behaves closer to zero," Golden said. "It's not unusual for a patient to come into a study, and behave very well from a diet and exercise [perspective] and start doing all those kinds of lifestyle modifications that the doctors like to talk to them about."
But patients don't often maintain those lifestyle changes for long, Golden added, which could aid a more robust Phase 3 program. "So as you go longer — 24 weeks, 48 weeks and beyond — the ability of the patient to really sustain a short-term benefit in placebo really goes away."
ROYAL-1 enrolled 105 hypercholesterolemia patients who were already taking older cholesterol drugs. The participants had existing LDL-cholesterol levels of at least 100 mg per deciliter and triglyceride levels of less than 500 mg per deciliter. Investigators also stratified the patients by their backgrounds with statin therapy and whether they were diabetic.
In addition to lower LDL-cholesterol, gemcabene hit in a secondary endpoint — reducing high-sensitivity C-reactive protein 40.0%. Conversely, the placebo group saw a 6.1% decline in hsCRP.
Gemphire leadership noted that, should their drug make it to market, the added benefit to hsCRP may help it outperform competitors.
"The data that we have to date, the doses that we're exploring, has been higher than most of the agents that have been out there," Golden said. "There are a couple of studies where a few of the agents get into the 30 and 40 percent range, but generally they're between 20 and 35 percent, so we look at that 40 percent reduction as quite meaningful and continues to be potentially part of the differentiation story for us."
Gemphire plans to more thoroughly evaluate the study's outcomes when it gets more complete data later this month. The company is also investigating gemcabene in severe hypertriglyceridemia, results from which are slated to come in the first quarter of 2018, as well as nonalcholic steatohepatitis, homozygous familial hypercholesterolemia, and other conditions.