GW Pharmaceuticals has seen its valuation more than double over the past six months on hopes for a childhood epilepsy project that effectively did not exist a year ago. And in a month or so the company will release the first clinical data on the cannabis-based compound, Epidiolex, collected from an early access programme that has been running in the US.
Hopes are already very high for this orphan disease project, and the data will be crucial in confirming its potential. An encouraging signal will also likely prompt an application for the FDA’s breakthrough therapy designation, chief executive Justin Gover tells EP Vantage. After struggling for years to bring its multiple sclerosis therapy Sativex to market, the the epilepsy programme could progress at a very different pace.
Proof of efficacy
The data due to emerge mid-year are from about 30 US children who have been receiving Epidiolex under expanded access INDs granted by the FDA over the past year. 300 children are now approved to receive the compound, and about 60 have started treatment, Mr Gover says.
GW is providing Epidiolex free under the early-access programme, but has asked prescribing physicians to follow preset protocols to track seizure frequency.
However, with funding and FDA approvals in place, GW has already shifted its focus to the clinical trials needed to get the project on the market. A phase II/III trial will start in the second half of the year in Dravet syndrome, a rare and severe treatment-resistant epilepsy with very poor prognosis. GW has already secured orphan drug designation in this indication, and in another form of severe childhood epilepsy called Lennox-Gastaut syndrome.
The plan is to have two phase III trials in each indication running in 2015, with a filing in 2016.
The primary aim is to establish that Epidiolex can reduce seizure frequency, and this is ultimately what will win approval, Mr Gover says. But safety and tolerability – these children are frequently on many other medicines – will also be closely watched.
“The safety profile for current drugs is a real problem. One of the attributes [that investors] hope and expect to see is a relatively benign safety profile,” he says.
Cannabinoids, and specifically cannabidiol or CBD, have long been recognised as potentially valuable anticonvulsants. Epidiolex is purified CBD – extracted from a plant grown to be rich in the compound – and formulated into a liquid, but medical marijuana practitioners have been selling CBD-enriched oils for some time.
It was US physicians keen to establish a reliable supply of CBD that triggered the Epidiolex programme about 18 months ago, Mr Gover says, and “remarkable benefits” were seen in the first patients treated. This caused demand to surge from the community of parents and physicians struggling to find effective treatments for their children.
After all this, Mr Gover says everybody would be “frankly astonished” if the data failed to show any signal of efficacy. And they will hopefully be good enough to warrant the FDA’s breakthrough therapy designation. “Very close dialogue with the FDA would be very useful in our case,” he says.
An expedited path to market would bring both clinical and commercial advantages. Insys Therapeutics, for example, has said it plans to file an IND in the second half of the year to move its synthetically produced CBD project into the clinic – it is also eyeing Dravet and Lennox-Gastaut syndromes.
Mr Gover says that, should GW win approval for its naturally derived compound, orphan exclusivity laws in the US would prevent any other CBD-based product – including man-made molecules – from being approved for the same uses for seven years.
He is very confident that GW is well ahead of any competition, pointing to the company’s 15 years of work in the area of cannabis-based medicines.
“We have a full preclinical toxicology and pharmacology package on CBD already. We have 200 patients who have been in clinical trials with CBD, albeit not children. And we also have over 20,000 patient years of safety data in Sativex, and CBD is half of Sativex. All these things together represent a starting point to engage with the FDA that the synthetic companies simply don’t have,” he says.
Falling into place
As Mr Gover describes it, the stars have aligned for GW over the last 12 months.
A serendipitous Nasdaq listing was launched in May 2013, allowing exuberant US investors to pile into the stock as the epilepsy story – which captured huge amounts of media attention in the country – gathered pace (GW’s Nasdaq glory provides a blueprint for European biotech, October 8, 2013).
Prior to its US listing the big milestone on the horizon was two phase III cancer pain studies being conducted with Sativex, by partner Otsuka. Due by year end and with the potential to lead to US approval and launch, the data remain an important event, although it is clear that epilepsy is now the key focus for investors.
This time last year the company's shares were trading at four-year lows and it was struggling to persuade the UK financial community to take it seriously. Today GW boasts a market cap of £741m ($1.3bn), US investors now account for more than half of its shareholders, and the daily trading volume of its stock has surged by 40 times.
“The fact that we have an orphan programme to which we own commercial rights is game-changing for GW. It’s a different story to a year ago.”
It will soon become apparent whether this story has a happy ending.