GW Pharma’s cannabinoid project Epidiolex looks like an odds-on favourite to win US approval for epilepsy after a drama-free FDA advisory committee meeting in which agency staff and expert consultants alike had virtually nothing negative to say about it.
The risk of liver enzyme elevations can be managed, the FDA staff told the adcom, while the potential for abuse appears to be low. When coupled with persuasive evidence that Epidiolex significantly reduced the frequency of seizures in patients with the severe Dravet and Lennox-Gastaut disorders, agency advisors voted 13-0 in support, making US approval by the decision deadline of June 27 highly likely.
The data package supporting Epidiolex, an oral liquid medicine derived from cannabis plants, indicated that it reduced seizure frequency by as much as 23% compared with placebo. In these rare and intractable forms of paediatric epilepsy regulators’ tolerance for risk is relatively high, but the debate nevertheless centred on safety – specifically, risk of liver injury and abuse.
Epidiolex was linked with an increased rate of liver enzyme elevations, with evidence of a dose response as 16% of patients taking a daily dose of 20mg/kg and 8% of those taking 10mg/kg experienced liver side effects. FDA officials noted that none of the elevations were high enough to indicate significant liver injury, and that the risk was linked to concomitant treatment with Depakote.
Label warnings and instructions about monitoring patients should be sufficient to limit the risk, the FDA staff said, although they cautioned that Epidiolex had not been studied in patients with underlying liver disease.
The panel also considered the drug’s potential for abuse. At the highest therapeutic dose, 20mg/kg, and a supratherapeutic 4,500mg, there were some signs of elevated risk, but the signal was significantly weaker than those of Xanax or Marinol, the pharmaceutical-grade tetrahydrocannabinol (THC) used as an antiemetic.
In particular, panel members wondered if a mild signal of euphoria might be down to residual THC in Epidiolex, but agency officials said maximum serum concentration of THC was much lower in patients taking Epidiolex than in those taking Marinol.
Nevertheless, Epidiolex will need to be reviewed by the US Drug Enforcement Agency and put on a schedule before it can be launched, which will take up to 90 days after the FDA decision date.
GW has said it plans to launch Epidiolex solo, and appears to be in a position to do so with more than $500m in cash at the end of 2017. EvaluatePharma’s consensus of sellside analysts forecasts sales of $1.6bn in 2022.
Having a near-market orphan drug makes GW an attractive acquisition target, of course, and regulatory catalysts could serve as a trigger for a deal. However, its $3.7bn market capitalisation might be a restraint on deal talks, since any buyout would need to be pitched higher than that – though thanks to tax reform US big pharma has hundreds of billions of dollars of overseas profits it can now access.
Investors expect those dollars to be put to good use – if the stigma of a cannabis-based technology can be overcome, then buying out GW could be one way to address those calls.