GW Pharmaceuticals’ U.S. subsidiary Greenwich Biosciences reported positive top-line results of a randomized, double-blind, placebo-controlled phase 3 clinical trial of Epidiolex in the treatment of seizures associated with tuberous sclerosis complex, a rare and severe form of childhood-onset epilepsy.

Epidiolex, is the first prescription, plant-derived cannabinoid medicine and the first in a new class of anti-epileptic medications approved in the United States to treat seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome in patients two years of age or older.

The current trial focused on tuberous sclerosis complex (TSC), a rare genetic condition that causes tumors to grow in many different organs of the body. Almost all of these tumors are benign and grow most often in the brain, skin, heart, eyes, kidneys and lungs and can cause a variety of health problems. Symptoms usually appear before a child is six months old and severity of the disease can vary widely. Epilepsy is present in greater than 90 percent of patients with TSC and may progress to become intractable to medication.

Patients aged one to 65 years with a confirmed diagnosis of treatment-resistant TSC were eligible to participate in the phase 3, randomized double-blind placebo-controlled trial. The trial randomized 224 patients into three arms: a lower dose, a higher dose, and a placebo. Epidiolex was added to current anti-epileptic drug treatment. The average age of trial participants was 14 years. On average, patients were taking three anti-epileptics, having previously tried and discontinued four other anti-epileptics.

TSC-associated seizures, as measured in the primary endpoint of this trial, differ from previous Epidiolex clinical trials in LGS and Dravet syndrome. These seizure types comprise focal motor seizures without impairment of consciousness or awareness; focal seizures with impairment of consciousness or awareness; focal seizures evolving to bilateral generalized convulsive seizures; and generalized seizures (tonic–clonic, tonic, clonic, or atonic) that are countable. The median baseline seizure frequency of the TSC-associated seizure types was 57 per month.

The primary endpoint of the study was the change in seizure frequency over the 16-week treatment period (four-week titration followed by 12-week maintenance at the target dose) compared to baseline for the lower dose Epidiolex arm vs. placebo. The results for both the lower dose and higher dose arms were similar, with seizure reductions of 48.6 percent and 47.5 percent from baseline, respectively, versus 26.5 percent for placebo. All key secondary endpoints were supportive of the effects on the primary endpoint. Both doses studied in the trial were shown to be equally effective, with fewer adverse events in the lower dose cohort. Adverse events included somnolence, decreased appetite, diarrhea, constipation, vomiting, transaminase elevations, pyrexia, seizure, cough, and infections.

“The positive outcome in this trial of Epidiolex in patients with tuberous sclerosis complex expands both our knowledge of this newly available medicine and its potential utility beyond the current indications,” said Elizabeth Thiele, director of the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital, professor of Neurology at Harvard Medical School, and the lead investigator of the trial. “Data from previous controlled clinical trials of Epidiolex have shown clinically meaningful seizure reductions and consistent safety and tolerability in children and adults with Lennox-Gastaut syndrome and Dravet syndrome. Based on the positive results of this trial in TSC patients, EPIDIOLEX, if approved for this additional indication, may become an important treatment option also in this disease state with significant unmet medical need.”

The trial was the fifth successful late stage study of Epidiolex for seizure control. Based on the current trial results, GW plans to submit an application to the U.S. Food and Drug Administration in the fourth quarter of 2019 with the goal of expanding the product label in 2020 to include TSC.

“Some of the most challenging and frustrating aspects of tuberous sclerosis complex are seizures that cannot be effectively controlled by existing medications,” said Kari Luther Rosbeck, president and CEO of the Tuberous Sclerosis Alliance, “A new safe and effective treatment option such as Epidiolex is desperately needed. We are truly excited about the potential approval of Epidiolex to treat seizures in TSC as it brings much needed hope to those with TSC and their families who live daily with this difficult disorder.”

Photo: Kari Luther Rosbeck, president and CEO of the Tuberous Sclerosis Alliance

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