Epidiolex Received Priority Review By The US FDA To Treat Tuberous Sclerosis (TSC) -related Epilepsy

- May 12, 2020-

British pharmaceutical company GW Pharma is a global leader in the science, development and commercialization of cannabinoid prescription drugs. Recently, the company and its US subsidiary Greenwich Biosciences announced that the US Food and Drug Administration (FDA) has accepted a supplemental new drug application (sNDA) for the oral liquid preparation of the cannabinoid drug Epidiolex (cannabidiol, cannabidiol, CBD) and Priority review was granted. The sNDA seeks to expand the Epidiolex label to include: treatment of seizures associated with tuberous sclerosis (TSC). The FDA has designated the sNDA's prescription drug user fee method (PDUFA) target date to be July 31, 2020. Last month, GW also submitted a Class II change application to the European Medicines Agency (EMA) seeking approval for the drug (European market name: Epidyolex) for the same indications described above.


If approved, this will be the third indication for Epidyolex / Epidiolex in the US and Europe. Previously, the drug has been approved in the United States and the European Union for patients 2 years of age and older, as an adjunct to the treatment of epilepsy associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS). In the United States and the European Union, Epidyolex / Epidiolex have been granted orphan drug qualifications for the treatment of DS, LGS, and TSC-related seizures, each of which is a rare, severe, childhood-onset drug-refractory epilepsy type.


TSC is a rare, serious, childhood inherited disease. Epilepsy is the most common neurological feature of TSC. As many as two-thirds of TSC patients will experience drug-refractory seizures. There is a major need for new treatment methods in solving TSC-related seizures. Data from a phase III clinical study showed that Epidiolex significantly reduced TSC-related refractory seizures (both focal and systemic) and improved the patient's overall condition compared to placebo. If approved, Epidiolex will provide an important treatment option for the TSC patient population.


tsc

Tuberous sclerosis syndrome-TSC (Source: childneurologyfoundation.org)


This new indication application is based on the results of a randomized, double-blind, placebo-controlled phase III clinical study. A total of 224 patients (age 1-65 years) were diagnosed as resistant to treatment (refractory) in the study. These patients were randomly assigned to receive Epidiolex 25 mg / kg / day (n = 75), Epidiolex 50 mg / kg / day (n = 73), placebo (n = 76), 16 weeks of treatment (4-week titration period, 12-week maintenance period). The primary endpoint was the percentage change from baseline in Epidiolex versus placebo during treatment compared with the frequency of TSC-related focal and systemic seizures. Key secondary endpoints include: proportion of patients with ≥50% reduction in seizures, proportion of patients with ≥50% reduction in total seizure frequency (including focal sensation and seizures), and overall impression of changes in the overall status of the subject / caregiver (S / CGIC).


The results showed that the study reached the primary endpoint. Compared with the placebo group, the frequency of TSC-related seizures in the Epidiolex treatment group was significantly reduced: the Epidiolex 25mg / kg / day treatment group and the 50mg / kg / day treatment group decreased by 49% from baseline. 48%, 27% reduction in the placebo group (p = 0.0009, p = 0.00118).


The results of all key secondary endpoints support the impact on the primary endpoint. Specifically: (2) Compared with the placebo group, a higher percentage of patients in the Epidiolex treatment group had a 50% or greater reduction in seizures (36% in the 25mg / kg / day group and 50mg / kg / day group) 40%, 22% in the placebo group, p = 0.0692 and p = 0.0245). (2) Compared with the placebo group, 48% of patients in the two-dose Epidiolex treatment group experienced a greater reduction in total seizure frequency (including focal sensation and seizures), compared with 27% in the placebo group ( p = 0.0013 and p = 0.0018). (3) According to the results of the patient / caregiver overall impression (S / CGIC) questionnaire survey, the proportions reported by the Epidiolex 25mg / kg / day group and Epidiolex 50mg / kg / day group were improved by 69%, 62%, and comfort, respectively The dosage group was 39% (p = 0.0074 and p = 0.0580). (4) Additional analysis showed that patients treated with Epidiolex experienced a greater reduction in compound focal seizures than patients with placebo (25 mg / kg / day treatment group, 50 mg / kg / day treatment group 52% and 50%, respectively, and 32% in the placebo group, p = 0.0076 and p = 0.0116).


The safety profile observed in this study is consistent with previous research results and no new safety risks have been identified. The incidence of adverse events (AE) was 93% in the 25 mg / kg / day group, 100% in the 50 mg / kg / day group, and 95% in the placebo group. Both doses have acceptable safety, with 25 mg / kg / day adverse events less than 50 mg / kg / day. The most common adverse reactions are diarrhea, decreased appetite and drowsiness.


Epidiolex


Tuberous sclerosis (TSC) is a rare genetic disease that affects approximately 50,000 people in the United States and nearly 1 million people worldwide. Globally, at least 2 TSC babies are born every day, and it is estimated that one in every 6000 newborns. The disease mainly causes benign tumors to grow in important organs of the body, including the brain, skin, heart, eyes, kidneys, and lungs, and is the main cause of hereditary epilepsy. TSC usually occurs in the first year after birth, manifests as focal epilepsy or infantile spasms, and is associated with an increased risk of autism and intellectual disability. The severity of the condition may vary widely. In some children, the disease is very mild, while others may have life-threatening complications. About 85% of TSC patients have epilepsy and may develop refractory to medication. More than 60% of TSC patients cannot control seizures through standard treatments such as antiepileptic drugs, epilepsy surgery, ketogenic diet, or vagal stimulation. In contrast, 30-40% of epilepsy patients without TSC are resistant.


Epidyolex / Epidiolex is an oral, high-purity liquid extract of CBD extract. CBD is a non-psychotropic component derived from the cannabis plant and has multiple pharmacological effects on the nervous system. A large number of studies have shown that CBD has obvious antiepileptic and anticonvulsant activities, and has fewer side effects than existing antiepileptic drugs.


Epidyolex / Epidiolex is the first plant-derived cannabinoid drug approved by the United States and Europe to treat epilepsy, and it is also the first new antiepileptic drug (AED). In the United States, Epidiolex was approved in June 2018. In the European Union, Epidyolex was approved in June 2019. The industry is very optimistic about the drug's commercial prospects. Clarivate has previously predicted that the sales in 2022 will reach $ 1.2 billion.


Currently, GW Pharmaceuticals is developing Epidiolex / Epidyolex for the treatment of other rare diseases including TSC and Rett syndrome. GW has launched Sativex (nabiximols), the world ’s first plant-derived cannabinoid prescription drug, which is approved by many outside the United States for the treatment of spasticity in multiple sclerosis; To seek FDA approval. The company's pipeline has a series of cannabinoid candidates, including compounds for the treatment of epilepsy, autism, glioblastoma, and schizophrenia.