Pubdate: Mon, 04 Apr 2016
Source: Chicago Tribune (IL)
Copyright: 2016 Chicago Tribune Company
Author: Robert McCoppin


Clinical Trial Shows Reduced Seizures in Children, Possibly 
Increasing Chances of FDA Approval

A marijuana extract significantly reduced seizures in severely 
epileptic children, according to a landmark study conducted in part 
at Lurie Children's Hospital of Chicago.

Supporters said the results greatly improve the chances for the drug, 
called Epidiolex, to win eventual approval by federal regulators for 
prescription use to treat Dravet syndrome, a debilitating type of 
epilepsy that strikes in early childhood. The drug would be the first 
derived from the marijuana plant to win such approval.

More broadly, the findings also support claims made by advocates of 
medical marijuana, but represent a much more controlled and limited 
use of the plant.

Children with Dravet syndrome typically have frequent seizures that 
cause problems with language, motor skills and relating to others. In 
the case of one patient in the trial at Lurie, 5-year-old Caleb Yunk, 
the disease has not been as severe but caused chronic seizures that 
led to difficulties with skills such as running, jumping and balancing.

In the trial, Caleb swallowed about 3 milligrams of a 
strawberry-flavored syrup twice a day. Once he started treatment, his 
parents said, the Milwaukee-area boy went 100 days without a seizure, 
and those he did have lasted less than half as long. Because Caleb's 
seizures can be triggered by overheating, his parents had kept him 
indoors on hot days, but on the drug, he showed enough progress to go 
swimming with his friends.

"His eyes sparkle more," said his mother, Kelley Yunk. "He's more 
engaged. I think he's more cheerful. For our family, it was such a 
huge blessing."

Much of the improvement came from being able to take Caleb off 
another drug and reduce his use of two others - medication that has 
serious side effects and made him "dopey," his parents said. Side 
effects seen during the Epidiolex trial included sleepiness, diarrhea 
and decreased appetite but were mostly mild or moderate, according to 
the manufacturer's reported results.

Epidiolex is almost pure cannabidiol, or CBD, a nonpsychoactive 
compound found in marijuana, without the THC component that gets users high.

The study at Lurie was part of a nationwide clinical trial conducted 
by the drug's maker, GW Pharmaceuticals. While a preliminary study 
also produced encouraging results, the company said this was the 
first trial of plant-based CBD involving a randomized, double-blind 
placebo control, known as the gold standard of disease research.

Double-blind means neither the patient nor the researchers know 
whether the patient is getting the drug or a placebo, in this case a 
similar liquid that doesn't contain any medicine, to avoid results 
being biased by optimistic interpretations.

The study involved about 120 patients, ages 2-18, who have Dravet 
syndrome and whose seizures were resistant to existing medications. 
Among patients who received the drug, convulsive seizures were 
reduced by an average of 39 percent, compared with 19 percent for the 
placebo, over 14 weeks last summer, according to results announced in March.

Officials are hopeful that this will speed up approval by the U.S. 
Food and Drug Administration to make Epidiolex available by prescription.

The study is one of four trials of Epidiolex to treat Dravet and a 
similarly serious form of epilepsy known as Lennox- Gastaut syndrome. 
Both conditions are rare, with an estimated combined patient 
population of roughly 30,000, and Dravet has no FDA-approved 
medication specifically for its treatment.

The promising results mean the company will seek a review by the U.S. 
Food and Drug Administration by the end of this year and hopes to win 
approval to prescribe Epidiolex by the end of 2017, GW 
Pharmaceuticals CEO Justin Gover said. The drug has fast-track 
designation from the FDA.

Initially, Epidiolex would be only for children who have not 
responded sufficiently to other medications.

It's too early to predict the cost of the drug, Gover said, but the 
company hopes to persuade insurance companies to cover it.

"We're obviously delighted" with the results, he said, calling it a 
"significant milestone."

UK-based GW Pharmaceuticals already offers Sativex, a drug derived 
from marijuana that contains equal parts THC and CBD and treats 
muscle spasms and stiffness in multiple sclerosis patients in Europe 
and Canada, though it is not available in the U.S. except in trials.

In a disappointment for advocates, trials last year failed to show 
that Sativex worked better than a placebo for cancer pain overall. 
But some less-frail patients who had pain despite using opioids did 
benefit, so researchers said it merited further investigation. GW 
Pharmaceuticals also plans to test treatments for various other 
conditions, including glioma, an aggressive form of brain cancer.

Investors have sued GW Pharmaceuticals over its admission that its 
trials lacked sufficient financial controls. But that is strictly 
about accounting for the cost of trials and has nothing to do with 
the test results, which no one has questioned, said Stephen Schultz, 
vice president of investor relations.

"We believe the lawsuit is completely baseless and without merit," he said.

Company officials emphasized that Epidiolex is very different than 
marijuana, because it is formulated as a concentrate of just one 
component of the plant, with pharmaceutical controls to guarantee the 
same product in every dose.

But medical marijuana advocates consider the Epidiolex results as 
verification of what they have been saying for years based on 
patients' stories, that marijuana can help those with epilepsy, which 
affects about half a million children in the U.S.

Ross Morreale, chairman of the Medical Cannabis Alliance of Illinois 
and cofounder of marijuana grower Ataraxia, said state law requires 
lab tests to guarantee potency and purity of medical marijuana, and 
it is already helping patients with a variety of medical conditions, 
without waiting for federal approval.

Illinois children with epilepsy may qualify to access medical 
marijuana under state law, but it remains illegal under federal law, 
and many doctors here are reluctant or prohibited by their employers 
from recommending it.

The principal investigator for the study at Lurie hospital was Dr. 
Linda Laux, a pediatric neurologist who specializes in helping 
children with treatment-resistant epilepsy.

Epidiolex did bring some positive changes in the patients' behavior, 
attention and focus, as well as motor skills such as walking, she 
said. Patients have been able to continue taking the drug after the trial.

"These results are very exciting and significant," Laux said. "This 
is absolutely a ray of sunshine and hope for these families."

Morgan Murphy, spokeswoman for the Epilepsy Foundation of Greater 
Chicago, welcomed the study results, which made her optimistic that 
the drug will get FDA approval.

"We've been waiting so long for something to come around," she said. 
"We're getting such a positive reaction from patients. It's a great 
step forward."
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MAP posted-by: Jay Bergstrom