DUBLIN – Shares in GW Pharmaceuticals plc rose as much as 28 percent Monday on news that Epidiolex, its liquid formulation of plant-derived cannabidiol, hit the primary endpoint of a phase III trial in patients with Lennox-Gastaut syndrome (LGS), a rare and difficult-to-treat form of childhood-onset epilepsy. Following on from a positive read-out in March from a phase III trial in Dravet syndrome, another form of severe epilepsy, it’s further evidence that the drug has clinically significant anti-seizure effects, and it increases the company’s confidence of approval as it waits for a pre-NDA meeting date from the FDA.
London-based GW Pharma expects to file an NDA in both indications in the first half of 2017.
“These two positive trials provide a sizeable body of evidence supporting the efficacy and safety of Epidiolex in highly treatment-resistant forms of childhood-onset epilepsy,” GW CEO Justin Gover told analysts on conference call. “They also reinforce our view that Epidiolex represents an exciting potential new class of anti-seizure drug, which may lead to meaningful seizure management in otherwise treatment-resistant patients,” he added.
In the placebo-controlled study, those who received the drug (20 mg/kg/day) plus concomitant anti-epileptic medication (n=86), had a median 44 percent reduction in monthly seizure frequency vs. baseline, whereas those in the control arm (n=85) had a median drop of just 22 percent. Patients across the study had a median monthly frequency of 74 seizures at baseline. The result was statistically significant (p=0.0135). Additional sensitivity analyses “confirmed the robustness of this result,” GW chief medical officer Stephen Wright said on the call.
The magnitude of the reduction seen was “highly clinically relevant when taken in the context of other FDA-approved treatments for Lennox-Gastaut syndrome,” he said. “Of course, whilst treatment of any type of epilepsy is challenging, in this study we should bear in mind that these patients are particularly difficult to treat, having been treatment-resistant to an average of nine other anti-epileptic drugs,” Wright said.
The placebo response was higher in this trial than in the Dravet syndrome study – in which those on drug had a median 39 percent drop in monthly seizure frequency vs. a drop of 13 percent for those on placebo – but this was not a cause of concern, Stephen Schultz, vice president of investor relations, told BioWorld Today. “I think the placebo rate we saw in the LGS trial was well within the expected range.” (See BioWorld Today, March 15, 2016.)
The LGS study threw up no additional safety issues – the type and frequency of serious adverse events were similar to those seen in the earlier study. “Twenty [LGS] patients on Epidiolex experienced a serious adverse event, nine of which were deemed to be related to treatment, compared with four patients on placebo, where one was deemed to be treatment-related,” Wright said. Twelve patients in the treatment arm discontinued therapy due to adverse effects, whereas just one in the control arm did. All patients who completed the trial entered an open-label extension study.
Asked during the Q&A about the contribution of the anti-convulsant clobazam to the efficacy signal seen, without disclosing the data, Wright indicated that it did not confound the data. “We are able to say that efficacy on clobazam was good and that patients obtained good efficacy off clobazam,” he said. “There were patients who became completely seizure-free off clobazam, which is a very important observation.”
A second phase III trial in LGS has completed recruitment of 225 patients and is expected to read out late in the third quarter. Additional indications are also being actively pursued. Recruitment onto a phase III trial in tuberous sclerosis complex, a rare genetic condition characterized by the growth of benign tumors, epilepsy, developmental delay and autism-like symptoms, is ongoing. The company plans to commence recruitment onto a phase III in infantile spasm in the fourth quarter.
CEO Gover would not be drawn on price during the call’s Q&A session. “I think it’s premature on this call to talk about price today. We haven’t even filed the NDA yet,” he replied to one hopeful analyst that raised the issue. LGS affects about 30,000 people in the U.S., Gover said, 18,000-20,000 of whom are children. The trial recruited patients ages 2 to 55 years – the average age was 15 years, but 34 percent of participants were 18 or older. Drave syndrome affects about 5,000 to 6,000 patients in the U.S.
On the emotionally charged issue of Brexit, Gover’s position was very much business as usual. The company, being domiciled in the U.K., will continue to benefit from U.K. incentives, such as the patent box and R&D tax credits. If a regulatory regime emerges that is separate from the current European approval system “that’s ok,” he said.
Investor exuberance appeared to be more muted on Wall Street than in London, as U.S. investors grappled with the implications of Brexit. The stock (NASDAQ:GWPH) gained $5.18 on Monday, to close at $88.49. Shares in London (AIM:GWP) shed some of the day’s gains during the afternoon, to close at £5.665 (US$7.49), up 11 percent.