FDA Approves First Marijuana-Based Prescription Drug

By Pat Anson, Editor

The U.S. Food and Drug Administration has approved the use of Epidiolex, the first drug derived directly from marijuana, to treat seizures caused by two rare and severe forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome.

Epidiolex is the first FDA-approved medication that contains cannabidiol (CBD), one of the active ingredients in marijuana. It does not contain tetrahydrocannabinol (THC), the chemical compound in marijuana that makes people high.

“This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition,” FDA commissioner Scott Gottlieb, MD, said in a statement.

.png.png

FDA approval of Epidiolex is a major milestone for GW Pharmaceuticals, a British company focused on developing CBD-based medications. The company said Epidiolex would be available in the fall, but did not disclose the price. Some analysts have predicted it could cost as much as $25,000 a year.

Many oils and tinctures containing CBD are already sold online and in states were medical marijuana is legal, but the FDA has not approved any of them. The agency has only approved a handful of synthetic cannabinoids such as Marinol (dronabinol) to treat loss of appetite and nausea.

“We’ll continue to support rigorous scientific research on the potential medical uses of marijuana-derived products and work with product developers who are interested in bringing patients safe and effective, high quality products,” Gottlieb said.

“But, at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims. Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.”

Some children in clinical trials experienced side effects from Epidiolex such as liver toxicity, anemia and drowsiness, but an FDA staff report said the risks were “mild to moderate” and could be managed with warning labels. The staff report also found there was low risk of the strawberry flavored Epidiolex being abused.

“Today’s approval of Epidiolex is a historic milestone, offering patients and their families the first and only FDA-approved CBD medicine to treat two severe, childhood-onset epilepsies,” Justin Gover, GW Pharmaceutical’s CEO, said in a statement.

“This approval is the culmination of GW’s many years of partnership with patients, their families, and physicians in the epilepsy community to develop a much needed, novel medicine. These patients deserve and will soon have access to a cannabinoid medicine that has been thoroughly studied in clinical trials, manufactured to assure quality and consistency, and available by prescription under a physician’s care.”

While Epidiolex is only approved for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, doctors will presumably be able to prescribe it “off label” for other conditions such as chronic pain.  

GW Pharmaceuticals also makes Sativex, an oral spray that contains both CBD and THC. Sativex has been approved in Europe, Canada, Australia, New Zealand and several other countries for the treatment of muscle spasticity caused by multiple sclerosis. In Israel, Sativex is also approved for the treatment of pain and chronic non-cancer pain.  

FDA Staff Recommends Approval of Marijuana Drug

By Pat Anson, Editor

The U.S. Food and Drug Administration may be on the verge of approving its first prescription drug derived directly from marijuana.

In a report posted online, FDA staff said there was “substantial evidence” that Epidiolex, a liquid formula containing cannabidiol (CBD), was effective in reducing seizures in children with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), two severe forms of childhood epilepsy.

GW PHARMACEUTICALS IMAGE

GW PHARMACEUTICALS IMAGE

Epidiolex is made by GW Pharmaceuticals, a British drug maker that specializes in developing drugs from marijuana.

“The applicant has provided positive results from three randomized, double-blind, placebo-controlled studies conducted in patients with LGS and DS,” FDA staff reported.

“The studies are adequate and well-controlled. The statistically significant and clinically meaningful results from these three studies provide substantial evidence of the effectiveness of CBD for the treatment of seizures associated with LGS and DS.”  

CBD is one of the active ingredients in marijuana. It does not contain THC (tetrahydrocannabinol), the chemical compound in marijuana that makes people high. Many oils and tinctures containing CBD are already sold online and in states were medical marijuana is legal, but the FDA has not approved any of them.  The agency has only approved a handful of synthetic cannabinoids such as Marinol (dronabinol) to treat loss of appetite and nausea.

Although some children in the clinical trials experienced side effects from Epidiolex such as liver toxicity, anemia and drowsiness, the FDA staff report said the risks were “mild to moderate” and could be managed with warning labels. The report also found there was low risk of the strawberry flavored Epidiolex being abused.

“Although the review is still ongoing, the risk-benefit profile established by the data in the application appears to support approval of cannabidiol for the treatment of seizures associated with LGS and DS,” the report concludes.

(4/18/18 Update: An FDA advisory committee unanimously recommended that the FDA accept the staff findings and approve Epidiolex) 

In a briefing paper for the committee, GW Pharmaceuticals said there were few effective treatment options for children with LGS and DS, who often have severe intellectual and developmental disabilities and a high risk of mortality.

A final decision by the FDA is expected this summer. There is no guarantee the agency will follow the advice of its staff or advisory committee. If Epidiolex is approved, it would only be for the treatment of childhood epilepsy. However, doctors would presumably be able to prescribe it “off label” for other conditions such as chronic pain.  

GW Pharmaceuticals also makes Sativex, an oral spray that contains both CBD and THC. Sativex has been approved in Europe, Canada, Australia, New Zealand and several other countries for the treatment of muscle spasticity caused by multiple sclerosis. In Israel, Sativex is also approved for the treatment of pain and chronic non-cancer pain.  

Results of Cannabis Drug Study Cause Market Frenzy

By Pat Anson, Editor

A British pharmaceutical company has reported positive results from a Phase 3 clinical study of a marijuana-based medication for Dravet syndrome, a severe form of children’s epilepsy.

The study found that Epidiolex, a liquid formula containing a plant-derived cannabinoid (CBD), significantly reduced the number of seizures in children with Dravet syndrome. CBD is a compound in cannabis that does not produce the “high” caused by marijuana.

The study findings caused shares of GW Pharmaceuticals (NASDAQ: GWPH) to more than double in trading Monday, much of it fueled by speculation that the company’s cannabinoid products would eventually be approved by the Food and Drug Administration for pain relief.

“If they get this, doctors will say, here’s a cannabinoid prescription,” said CNBC’s Jim Cramer. “This will be the pure cannabis that a lot of people who have been waiting for, an actual painkiller that is not addictive. This will replace, I believe, the terrible, terrible wave of death that oxycodone has caused.

image courtesy gw pharmaceuticals

image courtesy gw pharmaceuticals

“If you want to prescribe actual medical marijuana, a real doctor is reluctant to do it because there are no uniform standards, and what you really want is the pure cannabinoid. There will be use of this galore.”

In a statement to CNBC, GW said it was not investigating Epidiolex for pain relief.

"Today's Phase 3 results of Epidiolex (cannabidiol) were not studying the medicine as a possible treatment for pain. Epidiolex is being investigated for Dravet syndrome, Lennox-Gastaut syndrome and Tuberous Sclerosis Complex (TSC), three rare, extremely debilitating epilepsy syndromes that begin in infancy or early childhood," the company said.

The Phase 3 placebo controlled study involved 120 children with Dravet syndrome, who were averaging about 13 seizures a month before the trial began. Seizures declined by over a third in patients treated with Epidiolex, with few side effects.

“The results of this Epidiolex pivotal trial are important and exciting as they represent the first placebo-controlled evidence to support the safety and efficacy of pharmaceutical cannabidiol in children with Dravet syndrome, one of the most severe and difficult-to-treat types of epilepsy,” said Orrin Devinsky, MD, of New York University Langone Medical Center’s Comprehensive Epilepsy Center.

“These data demonstrate that Epidiolex delivers clinically important reductions in seizure frequency together with an acceptable safety and tolerability profile, providing the epilepsy community with the prospect of an appropriately standardized and tested pharmaceutical formulation of cannabidiol being made available by prescription in the future.”

Epidiolex has both Orphan Drug Designation and Fast Track Designation from the U.S. Food and Drug Administration. There are currently no approved treatments for Dravet syndrome in the U.S.

“We are excited about the potential for Epidiolex to become the first FDA approved treatment option specifically for Dravet syndrome patients and their families,” said Justin Gover, GW’s CEO. “In light of this positive data, we will now request a pre-NDA (new drug application) meeting with the FDA to discuss our proposed regulatory submission.”

GW is recruiting 150 patients for a second Phase 3 trial of Epidiolex for Dravet syndrome and is currently conducting a Phase 3 study for Lennox-Gastaut syndrome. Another study of Epidiolex is scheduled to begin soon for a third form of epilepsy, Tuberous Sclerosis Complex.

The company is already marketing a marijuana-based oral spray called Sativex that is being sold in Europe, Canada and Mexico to treat muscle tightness and contractions caused by multiple sclerosis. Canada also allows Sativex to be used for the treatment of neuropathic pain and advanced cancer pain.

Sativex is not currently approved for use in the U.S. for any condition. It is estimated that over 400,000 cancer patients in the U.S. suffer from pain that is not well controlled by opioid pain medications. Two recent Phase 3 studies found that Sativex worked no better than a placebo in treating cancer pain.

New Setback for Medical Marijuana Spray

By Pat Anson, Editor

A British drug maker has announced more disappointing results from clinical studies on the use of a medical marijuana spray to treat cancer pain.

GW Pharmaceuticals (NASDAQ: GWPH) said results from two new Phase III studies showed that its Sativex oral spray worked no better than a placebo in treating cancer pain. That was the same finding the company reported in January from an earlier study involving nearly 400 patients in the United States, Mexico and Europe.

However, patients in the U.S. did show “statistically significant improvement” in their pain levels when Sativex was taken along with an opioid pain medication. GW and its partner, Otuska Pharmaceutical, have requested a meeting with the U.S. Food and Drug Administration to explain that finding. Sativex is getting a “fast track” review from the agency as a treatment for cancer pain.

"In light of the missed primary endpoint in the first trial earlier this year, these additional results are not a surprise. Nevertheless, we are encouraged by data across the trials which consistently show positive outcomes for U.S. patients when analysed as a separate cohort," said Justin Gover, GW's Chief Executive Officer.

image courtesy of gw pharmaceuticals

image courtesy of gw pharmaceuticals

"We believe that this finding may provide important guidance in determining the optimal target patient population for Sativex and look forward to a discussion with the FDA on a potential path forward."

Sativex is composed primarily of two cannabinoids, CBD and THC, which are administered in an oral spray. Sativex is already being sold in Europe, Canada and Mexico to treat muscle tightness and contractions caused by multiple sclerosis. Canada also allows Sativex to be used for the treatment of neuropathic pain and advanced cancer pain.

The spray is not currently approved for use in the U.S. for any condition. It is estimated that over 400,000 cancer patients in the U.S. suffer from pain that is not well controlled by opioid pain medications.

"While the results overall have been disappointing, and not necessarily wholly consistent with clinical experience, nonetheless they suggest that Sativex may have a useful role in the treatment of certain subgroups of patients with advanced cancer pain who have exhausted opioid treatments," stated Dr. Marie Fallon, Professor of Palliative Care, University of Edinburgh and a principal investigator in the Phase III program.

"In particular, the U.S. patients enrolled in this program showed a useful therapeutic benefit whereas results in European patients were generally not favorable. These U.S. patients were less frail, hence the Sativex intervention was subjected to less ‘noise,’ providing clearer results and valuable guidance in determining the optimal target patient population for Sativex. This is a patient population with a significant unmet need and I believe that this important observation for Sativex warrants further investigation."

Cancer patients in all three studies were given Sativex or a placebo spray 3-to-10 times a day over a 5-week period. Patients remained on opioid therapy during the studies. Sativex was well tolerated, with the only side effects in some patients being dizziness and somnolence.

GW is developing other cannabis-based medicines to treat epilepsy, glioma, ulcerative colitis, type-2 diabetes, and schizophrenia.