GW Pharmaceuticals’ GWP42006 has failed to outperform placebo in a phase 2a focal seizure trial. The setback wiped 5% off GW’s stock and dented the prospects of the cannabidivarin candidate.
Investigators enrolled 162 adults with inadequately controlled focal seizures and randomized them to receive GWP42006 or placebo. GW designed the proof-of-concept trial to assess whether GWP42006 cuts the frequency of seizures. A positive outcome would have boosted GW’s hopes of developing drugs based on cannabidivarin, a different cannabinoid than is used in lead asset Epidiolex.
The outcome fell short of expectations, though. While the trial linked GWP42006 to around a 40% drop in focal seizures, the placebo triggered a similarly sharp decline, resulting in the study missing its primary endpoint.
That is a blow to GWP42006 but in GW’s eyes the setback isn’t terminal. The cannabinoid specialist is still planning to move the asset into the clinic in autism spectrum disorders and Rett syndrome. And it will continue to explore whether it has a future in epilepsy, despite it failing to best placebo in the phase 2a.
GW is still working to understand what drove the placebo response. But it made a point of noting the trial was mainly performed at Eastern European sites in its statement to disclose the results. Some researchers have posited a link between the globalization of clinical trials and an uptick in placebo response rates, particularly in CNS studies.
One meta-analysis of adjunctive-therapy partial epilepsy trials found placebo response rates almost doubled between 1989 and 2009. The cause of the trend is unclear. But with an analysis of pediatric depression studies finding placebo response rates increase in line with the number of sites—and the 1989-2009 period covering the era of clinical trial globalization—some researchers have suggested the enrollment of patients in emerging markets may play a role.
Whatever is happening, GW isn’t the first drug developer to be stung by the phenomenon. UCB Pharma’s plans to win approval of epilepsy drug Briviact were set back when its European phase 3 trial failed, despite the U.S.-skewed study clearing the efficacy bar. The placebo response rate was fingered as the cause of the flop. One-third of the failed trial’s sites were in India or Eastern Europe. UCB went on to generate additional data and win approval for Briviact.
Many studies feature a similar mix of sites to the UCB trial and go on to deliver high-quality data that accurately reflect the safety and efficacy of their candidates. But GW ended up with a 40% placebo response rate and plenty of questions left to answer about the prospects of GWP42006.