DUBLIN – Shares in GW Pharmaceuticals plc shot up 17.2 percent percent Monday on news that Epidiolex, its liquid formulation of cannabidiol, reached the primary endpoint of a second phase III trial in treatment-resistant Lennox-Gastaut syndrome (LGS), a severe form of childhood epilepsy.

The data pave the way for an NDA filing in the first half of next year. The Cambridge, UK-based company plans to submit a single dossier that would support approval in both LGS and Dravet syndrome. The latter condition, a severe form of early onset epilepsy, is commonly associated with sporadic mutations in the SCN1A gene, which encodes a sodium channel. It reported positive phase III data in that indication earlier this year.

The new data are not only good – they're also strongly consistent with those obtained in the earlier study in LGS. Although the company has only unveiled topline data so far – it has yet to give an indication of responder rates – the magnitude of the responses seen across the two studies is of a similar scale.

In the second trial, those on 20 mg/kg/day (n=76) had a 42 percent reduction in the monthly frequency of drop seizure; those on 10 mg/kg/day (n=73) had a 37 percent reduction; while those in the placebo group (n=76) had a 17 percent reduction. Patients had a median baseline frequency of 85 drop seizures (defined as atonic, tonic or tonic-clonic, involving either the entire body, trunk or head) per month.

In the earlier, two-arm trial, those on 20 mg/kg/day (n=86) had a 44 percent reduction in the monthly frequency of drop seizures, while those in the placebo group (n=85) had a 22 percent reduction. Patients had a median baseline monthly frequency of 74 seizures in the earlier trial. (See BioWorld Today, June 28, 2016.)

Piper Jaffray analyst Joshua Schimmer highlighted the efficacy signal exhibited by the lower dose. "With a smaller enrollment per arm due to the addition of the lower dose, some investors feared loss of statistical significance along with no effect at the lower 10 mg/kg dose. Ultimately, both concerns proved unfounded, with high statistical significance [both arms p < 0.005]," he wrote in an investor note.

All patients in the second trial were on concomitant anti-epilepsy drugs – they were taking about three on average, having previously tried and discontinued an average of seven others. "In this demanding setting, we are especially pleased about the level of efficacy seen," GW Pharma's chief medical officer, Stephen Wright, told analysts on an investor call. Forty-nine percent of patients were taking clobazam, although Wright discounted any impact on the efficacy data. "We're very confident the research supports our previous position – that the positive effect of Epidiolex is independent of whether the patient is taking concomitant clobazam," he said.

The lower dose, although slightly less efficacious, appeared to be more tolerable. "In this trial, only one patient on the 10 mg/kg/day dose discontinued treatment due to adverse events, and six patients discontinued treatment on the 20 mg/kg/day dose," he said. Two of 13 serious adverse events in the low-dose arm were judged to be treatment-related, he said, vs. five of 13 in the high-dose arm. Eight patients in the control arm experienced serious adverse events. Ninety-nine percent of those who completed the trial joined an open-label extension study.

GW Pharma will file for approval of the two doses in LGS. So far, it only has data for one dose in Dravet syndrome. In a phase III trial reported in March, those on 20 mg/kg/day (n=61) had a 39 percent reduction in the monthly frequency of drop seizures, while those in the placebo group (n=59) had a 13 percent reduction. Patients had a median baseline frequency of 13 seizures per month. (See BioWorld Today, March 15, 2016.)

A second phase III trial in Dravet syndrome is underway, but the read-out will not come in time for the upcoming regulatory submission. On the basis of a pre-NDA meeting GW had with the FDA in mid-July, data from the single Dravet syndrome trial will suffice. GW CEO Justin Gover told analysts that the company expects the FDA to deliver its decision on the two indications at the same time. The dossier will contain data from 10 phase I and phase II studies and a safety database comprising 1,800 patients. More than 450 patients have been exposed to the drug for a year or more. Manufacturing scale-up is continuing in parallel. "We have been scaling significantly. We do expect to have inventory in year one for a few tens of thousands of patients," Gover said.

Epidiolex is a purified cannabis extract comprising 99 percent cannabidiol, with just trace amounts of other cannabinoids. In contrast, GW's approved product, the multiple sclerosis spasticity treatment Sativex, comprises equal parts cannabidiol and tetrahydrocannabinol.

GW shares (NASDAQ:GWPH) closed Monday at $126.06, up $18.50.