Zogenix hands GW a win
A phase III Lennox-Gastaut trial sees Fintepla meet statistical significance but fail the test of clinical relevance.
Zogenix’s claim yesterday to have succeeded in Lennox-Gastaut syndrome with its fenfluramine reformulation Fintepla is a case of putting a brave face on a disappointing dataset. The technically positive Fintepla result clearly underperformed GW Pharma’s Epidiolex in this childhood epilepsy indication.
The markets saw through Zogenix’s hype, sending its stock down 30% this morning while GW rose 7%. Not only does Epidiolex now have a clearer run at Lennox-Gastaut, if the latest result forces Zogenix to focus on Fintepla’s other use, Dravet syndrome, this could reduce the threat to Epidiolex of off-label Fintepla.
Epidiolex is marketed for both Dravet and Lennox-Gastaut, while Fintepla has a US FDA action date of March 25 in the former use. Evercore ISI analysts, who cover GW, said yesterday’s disappointing result would make Zogenix price Fintepla relatively high for Dravet, the smaller indication, limiting its off-label use.
What led to this was the Fintepla trial in 263 Lennox-Gastaut subjects that read out last night. Here the higher of two Fintepla doses, 0.7mg/kg/day, led to a 26.5% reduction from baseline in frequency of drop seizures, yielding a p value of 0.0012 versus placebo control.
So far, so good. But adjusting for placebo the reduction was only 18.7%. And the harsh reality is that the Epidiolex label reveals a 20-25% placebo-adjusted difference – in a study where placebo performed far better than in Zogenix’s trial.
This means that Fintepla simply lacks real-world clinical relevance. Zogenix argued that key secondary measures also favoured Fintepla, and an important aspect of the study was dose response: the lower 0.2mg/kg/day only beat placebo numerically, missing statistical significance.
However, this at best hints that only a dose higher than 0.7mg/kg/day could rival Epidiolex’s efficacy in Lennox-Gastaut. And any hopes of higher dosing will be tempered by fears over Fintepla’s active ingredient; fenfluramine was one half of the fen-phen obesity drug withdrawn in 1997 over links with serious heart problems.
Indeed, safety considerations could still play out as the FDA considers Fintepla’s Dravet filing. Zogenix says no serious cardiovascular issues have been observed, and again none were reported in the Lennox-Gastaut trial, where the most common adverse event was decreased appetite – logical for what had been designed as a diet drug.
Still, it will not go unnoticed that the full extent of fen-phen’s disastrous side-effect profile only emerged after broad patient use. This could weigh on the FDA reviewers’ minds as they evaluate Fintepla, and in the meantime the project’s second leg has been cut out from under it.
|GW versus Zogenix|
|Epidiolex (cannabinoid receptor agonist)||Status||Approved Nov 2018|
|2024e US sales||$118m||$380m|
|Fintepla (selective 5-HT reuptake inhibitor; Sigma-1 opioid receptor regulator)||Status||Filed||Phase III|
|2024e US sales||$219m||$308m|
|Source: EvaluatePharma US sales by indication.|