On Friday, clinical-stage drug developer Zogenix (NASDAQ:ZGNX) reported results from the first of two trials evaluating the use of low-dose fenfluramine (ZX008) in patients with a rare form of epilepsy called Dravet syndrome. The results demonstrated that this drug -- once the "fen" part of the failed obesity drug fen-phen -- may control seizures in patients better than GW Pharmaceuticals's (NASDAQ:GWPH) Epidiolex, a highly anticipated marijuana-based drug.

Targeting the toughest to treat

Dravet syndrome is a rare and difficult type of epilepsy. Typically, it's diagnosed during a child's first year of life, and usually, Dravet syndrome patients lag peers in language and motor skills development. Sadly, it's resistant to commonly used anti-seizure medications, which makes the need for new treatment options important.

A tablet showing a brain scan and the words epilepsy with a stethoscope wrapped around it.


Because Dravet syndrome patients suffer frequent seizures, Dravet syndrome patients require significant care, and absent better treatment options, the prognosis for patients is poor. Overall, there are about 16,000 people diagnosed with Dravet syndrome in the U.S. and Europe. 

Using marijuana to control epilepsy

GW Pharmaceuticals is a leader in the development of medicine derived from marijuana's chemical cannabinoids. It already markets a THC-based medicine in Europe for multiple sclerosis spasticity, and it's been working on a cannabidiol-based (CBD) medicine, Epidiolex, for use in hard-to-treat epilepsy for years.

There are a lot of empirical stories about the benefits associated with epilepsy patients use of marijuana that's high in CBD, but last year, GW Pharmaceuticals became the first drugmaker to scientifically prove in clinical studies that its use can significantly lower the monthly frequency of seizures in Dravet syndrome patients. 

In studies evaluating Epidiolex in both Dravet syndrome and Lennox-Gastaut syndrome, another rare form of childhood-onset epilepsy, it reduced monthly seizures from baseline by about 40%. That matched up favorably to the low teen percentages witnessed in the placebo arm of its studies.

Following the release of those results, GW Pharmaceuticals has said it plans to file for FDA approval soon. 

Zogenix drug may be better

With an FDA application looming, Epidiolex is in the lead, but today's ZX008 data suggests that it may work better, and if so, Epidiolex's first-mover advantage may not ensure it remains the standard of care if approved.

In Zogenix's ZX008 study, the rate of monthly seizures dropped by an average 64% and median 72% in the 0.8 mg arm of its study, which is significantly better than the median 17.4% drop in the placebo group. Management also said that 45% of patients saw a 75% or greater reduction in monthly seizure rate. For comparison, only 2.5% of patients in the placebo group achieved that level of benefit. Furthermore, the median longest seizure-free interval for ZX008 was about 20 days, or more than twice the interval witnessed in the placebo group.

These top-line results suggest ZX008 may be the best future treatment option available to Dravet patients, but only if doctors can be convinced that low-dose fenfluramine is safe. Fenfluramine is a serotonin-releasing drug that gained widespread notoriety in the 1990s as one of two drugs combined in the weight-loss drug Fen-Phen. Patients treated with Fen-Phen were found to be at greater risk of developing heart problems, including pulmonary hypertension. The risk was determined severe enough for the FDA to pull Fen-Phen from the market in 1997. 

Based on new data, it would seem that Zogenix might be able to demonstrate to doctors that ZX008 doesn't expose patients to the same cardiac risks associated with Fen-Phen. In its trial, adverse events were experienced by most patients; however, severe adverse event rates were roughly in line with placebo. and there were no occurrences of worrisome cardiac signals that would indicate similar concerns to Fen-Phen.

What's next

Epidiolex and ZX008 appear to work in Dravet syndrome patients. It's tempting to compare directly efficacy from their respective trials to decide which may be better, but that's bad science. No head-to-head trials that could show which of these drugs is better are planned, so doctors and patients will need to review all of the patient efficacy and safety data independently and then conclude which drug is best for their patients. 

It's also important to remember that GW Pharmaceuticals' Epidiolex has also proven to be effective in Lennox-Gastaut syndrome, and that's something Zogenix' hasn't proven yet for ZX008. Management did tell investors on its conference call that it plans to enroll an LGS study by the end of 2017. 

Additionally, an FDA filing for approval of ZX008 won't happen until a second Dravet syndrome confirms efficacy. Results from that second trial are anticipated in the first half of 2018. Overall, it may be too early to say that ZX008 will win more market share than Epidiolex if both drugs are approved, but the data so far suggests it's possible. 

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.