Cannabidiol

Articles · New Medicines ·
35022511000001100

Articles

New Medicines

Category

Bladder instillation

Epidyolex (EU), Epidiolex (US) · Treatment-resistant epilepsy in children inc. Dravet syndrome & Lennox-Gastaut syndrome

Information

Epidyolex (EU), Epidiolex (US)
New molecular entity
GW Pharmaceuticals
Greenwich Biosciences

Development and Regulatory status

Launched
Launched
Launched
October 2019
Yes
Yes
Apr 20 · Price= 100mg/ml oral soln, 100ml=£850.29 [38].
Jan 20 · GW announces the official launch of Epidyolex on 6 January 2020, and notes it is routinely commissioned in England, Wales and Northern Ireland [36].
Jan 20 · Epidyolex has been available via Phoenix UK since October 2019. Pack size - 100mg/mL x 100mL bottle. NHS trusts are advised to contact Phoenix UK direct for price [34].
Sep 19 · Approved in the EU [33]
Jul 19 · Recommended for EU approval by CHMP - the full indication is "for use as adjunctive therapy of seizures associated with Lennox‑Gastaut syndrome (LGS) or Dravet syndrome (DS), in conjunction with clobazam, for patients 2 years of age and older”. It is proposed that the medicine should be initiated and supervised by physicians with experience in the treatment of epilepsy [32].
Jun 19 · Uptake and sales of Epidiolex in the US have exceeded expectations, with 10,000 patients treated by April 2019 and sales of $33.5 million in its first full quarter on the market, more than double the anticipated $16 million figure [31].
Nov 18 · Launched in the US with a list price of $32,500 per year [29].
Oct 18 · Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It is also the first FDA approval of a drug for the treatment of patients with Dravet syndrome [27].
Sep 18 · GW Pharmaceuticals reports that Epidiolex has been transferred to Schedule V, the lowest restriction classification, by the US Drug Enforcement Administration. The company anticipates making Epidiolex available within the next 6 weeks [28].
Jun 18 · Approved in US. As part of the approval process, Epidiolex must be rescheduled from its current Schedule I before it can be made available to patients. Rescheduling is expected to occur within 90 days. GW subsidiary Greenwich Biosciences will market the drug in the US. Launch is expected autumn 2018 [25,26].
May 18 · GW Pharmaceuticals expects a decision regarding its MAA in Q1 19 [24].
Apr 18 · According to briefing documents posted to the FDA website ahead of an advisory committee meeting, the risk-benefit profile established by the data in the application appears to support approval. As no significant safety or efficacy issues were highlighted, it looks likely at this point that the FDA Peripheral and Central Nervous System Drugs Advisory Committee will recommend approval [23].
Dec 17 · GW Pharmaceuticals announce submission of Marketing Authorisation Application (MAA) to the EMA for Epidiolex® as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome. The MAA for Epidiolex is supported by data from three Phase 3 safety and efficacy studies, each of which met their primary endpoint.[21]
Oct 17 · Filed in the US - The company plans to file in the EU “in the near future” [20].
Apr 17 · GW hoping aiming to file in US in Q3 2017 [18]
Mar 17 · Granted orphan drug status in the EU for treatment of Lennox-Gastaut Syndrome (LGS) [16].
Sep 16 · GW has received guidance from the FDA that it considers is both positive and supportive of their proposed filing strategy to submit a single NDA for both the Dravet syndrome and Lennox-Gastaut syndrome indications incorporating the single Dravet trial that has already reported results and the two LGS trials [14].
Jun 16 · GW Pharma plan to file in US in H1 2017 for both Lennox-Gastaut and Dravet syndromes. GW has an upcoming pre-NDA meeting with the FDA on Epidiolex in Dravet syndrome, and it will request a separate meeting for the candidate in Lennox-Gastaut syndrome. But it does believe the indications are related and may be reviewed together [13].
Oct 14 · Granted orphan drug status in the EU for treatment of Dravet syndrome [5].
Jun 14 · GW anticipates starting anaother PIII trial in Dravet syndrome in 1Q 2015. GW expects to hold a pre-IND meeting with the FDA for Epidiolex in the treatment of LGS in mid-2014, and expects to conduct two PIII trials in LGS during 2015 [1].
Jun 14 · Epidiolex has been granted fast-track status and orphan drug status in the US [1].
Jun 14 · GW Pharmaceuticals plan to start a Phase 2/3 clinical trial of Epidiolex in Dravet syndrome in 2H 2014 [1].
Jun 14 · Pre-clinical for Dravet syndrome and Lennox-Gastaut syndrome in the UK [2].

Category

A small-molecule cannabinoid compound
Dravet Syndrome (UK prevalence 1 per 28,000) is a rare and extremely severe form of refractory epilepsy thought to be caused by a gene defect causing abnormal functioning of a sodium channel in the brain. Lennox-Gastaut syndrome (prevalence 2 per 10,000 in Europe) is characterised by multiple types of epileptic seizures, a characteristic electroencephalogram (EEG) with generalised slow spike-and-wave discharges, psychomotor delay and behavioural disorders [3,4].
Treatment-resistant epilepsy in children inc. Dravet syndrome & Lennox-Gastaut syndrome
Oral

Further information

Yes
December 2019
Lennox-Gastaut syndrome
Go to latest from NICE
Dravet syndrome
Go to latest from NICE

Trial or other data

Dec 19 · NICE recommends cannabidiol as an option for for treating seizures associated with Dravet syndrome and Lennox-Gastaut. There is a simple discount patient access scheme for cannabidiol [35].
Dec 19 · Second NICE TA in progress, due to indications (Lennox-Gastaut) [30].
Jan 18 · Results of GWPCARE4 (NCT02224690) published in The Lancet. 14-week study (n=171) found add-on cannabidiol (CBD 20mg/kg daily) was associated with a larger reduction in mean drop seizure frequency (-43.9% [IQR -69.6 to -1.9]) than placebo (-21.8% [-45.7 to 1.7]). Twelve patients (14%) in the CBD group withdrew due to adverse effects [22].
May 17 · PIII study (for which preliminary results were reported last Sep) published in NEJM. 43% of children on cannabidiol had a 50% reduction or better on seizure frequency vs. 17% with placebo, and 5% became entirely seizure-free with Epidiolex. Median number of seizures dropped from over 12 per month to less than six with placebo, and this was accompanied by a significant improvement on quality-of-life scores [19].
Apr 17 · Positive PIII data from GWPCARE3 study for Epidiolex in LGS presented at conference. The addition of cannabidiol to existing treatments in adults and children with LGS resulted in a larger median reductions in the monthly frequency of drop seizures (37-42% depending on dose) vs placebo (17%) [17].
Sep 16 · GW Pharma announces a second set of positive PIII results for cannabidiol to treat seizures in LGS. Patients on a high dose of Epidiolex saw a reduction in monthly drop seizures of 42%, while low-dose patients achieved a 37% decline and placebo patients saw a 17% reduction [15].
Jun 16 · GW Pharma announce data from a PIII trial involving 171 patients with LGS found that Epidiolex had a statistically significant median reduction in monthly drop seizures of 44% vs. 22% for placebo, during the 14-week treatment period. Patients in the trial had already been treated with an average of 9 antiepileptic drugs. Epidiolex patients reported an 86% rate of adverse events, as compared with 69% for placebo patients. The most common, occurring in more than 10% of patients, were diarrhea, somnolence, decreased appetite, pyrexia and vomiting. The company expects to report on a second, 225-patient PIII trial in this indication. This is a dose-ranging trial with three treatment arms with top-line data expected around the end of Q3 [12].
Mar 16 · GW Pharmaceuticals announces positive results of the first pivotal PIII study of cannabidiol (Epidiolex) for treatment of Dravet syndrome. Patients taking Epidiolex achieved a median reduction in monthly convulsive seizures of 39% vs. a reduction on placebo of 13% (p=0.01). A series of sensitivity analyses of the primary endpoint confirmed the robustness of this result. The difference between Epidiolex and placebo emerged during the first month of treatment and was sustained during the entire treatment period. Results from secondary efficacy endpoints reinforced the overall effectiveness observed with Epidiolex. Epidiolex was generally well tolerated in this study. The most common adverse events (occurring in greater than 10% of Epidiolex-treated patients) were: somnolence, diarrhoea, decreased appetite, fatigue, pyrexia, vomiting, lethargy, upper respiratory tract infection and convulsion. Of those patients on Epidiolex that reported an adverse event, 84% reported it to be mild or moderate. Ten patients on Epidiolex experienced a serious adverse event vs. three patients on placebo. Eight patients on Epidiolex discontinued treatment due to adverse events compared with one patient on placebo [11].
Dec 15 · Results of open label trial published in the Lancet neurology. In this single arm, open label study (214 enrolled patients) the median monthly reduction in frequency of motor seizures was 36.5% from a median baseline of 30.0 events per month. Serious adverse events were reported in 30% of patients [10].
May 15 · GW Pharmaceuticals begins a PIII trial of Epidiolex for LGS. GW anticipates that top-line data from the 14-week, 150-patient trial, which closely follows the start of two late-stage studies assessing the drug in another rare childhood epilepsy called Dravet syndrome, will be available early next year [9].
Apr 15 · In an open-label study reported at the American Academy of Neurology meeting, cannabidiol reduced the number of seizures by an average of 54% among patients with severe, treatment-resistant epilepsy [8].
Mar 15 · GW Pharmaceuticals has begun a PIII trial, the second part of a two-part randomised, double-blind, placebo-controlled parallel group safety, tolerability, pharmacokinetic and efficacy study of the drug in children treated with other anti-epileptic drugs. Part one - the pharmacokinetic and dose-finding elements of the trial - completed earlier this year. Part two is a 14-week comparison of Epidiolex versus placebo in a total of 100 patients to assess the drug’s safety and efficacy as an adjunctive anti-epileptic treatment. Top-line data should be available by the end of 2015, with a view of submitting a New Drug Application in the US mid-2016 [7].
Feb 15 · NCT02224703 A PIII Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome. Starts Mar 15, due to complete Dec 15. NCT02224690 A PIII Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults. Starts Mar 15, due to complete Dec 15 [6].
Oct 14 · The PII/III trial is a two-part randomised double-blind, placebo-controlled parallel group safety, tolerability, pharmacokinetic and efficacy study of single and multiple doses of epidiolex to treat Dravet Syndrome in children in addition to other anti-epileptic drugs. Part one will comprise the pharmacokinetic and dose-finding elements in 30 pts over 3 weeks and part two will be a placebo-controlled safety and efficacy evaluation over 3 months in 80 pts. All pts who complete the study will be eligible to enter an open label extension study.[6]
Oct 14 · PII/III trial commenced in the US. An additional Phase 3 trial is anticipated in the 1st quarter of 2015 in parallel with part two of the first PII/III trial [6].
Jun 14 · GW Pharmaceuticals announce physician reports of efficacy and safety data on 27 children and young adults with treatment-resistant epilepsy who have been treated with cannabidiol, Epidiolex, for a period of 12 weeks. Uncontrolled data from two hospital sites in the US that were generated under expanded access Investigational New Drug applications (INDs) authorised by the FDA were made available to the Company. A high proportion show a reduction in seizure frequency of greater than 50% and a portion of patients were reported to be seizure-free at the end of 12 weeks of treatment [1].

Evidence based evaluations

Epidyolex (EU), Epidiolex (US) · Epilepsy in patients with tuberous sclerosis complex who experience inadequately-controlled focal seizures - add-on therapy

Information

Epidyolex (EU), Epidiolex (US)
Licence extension / variation
GW Pharmaceuticals
Greenwich Biosciences

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)
Yes
Yes

Category

A small-molecule cannabinoid compound
Tuberous sclerosis complex (TSC) is a genetic disorder that causes non-malignant tumors to form in many diffferent organs, e.g. brain, eyes, heart, kidney, skin and lungs. TSC is estimated to affect approximately 50,000 patients in the U.S and 1 million people worldwide. The most common symptom of TSC is epilepsy, which occurs in 75-90% of patients, about 70% of whom experience seizure onset in their first year of life. Approximately 60% of TSC patients have treatment-resistant seizures [1,2].
Epilepsy in patients with tuberous sclerosis complex who experience inadequately-controlled focal seizures - add-on therapy
Oral

Evidence based evaluations

Zygel · Fragile X syndrome in paediatric and adolescent patients

Information

Zygel
New formulation
Zynerba Pharmaceuticals
Zynerba Pharmaceuticals

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase III Clinical Trials
Yes

Category

Cannabinoid receptor CB1 antagonist.
Rare, affecting ~ 1 in 4,000 males and 1 in 6,000 to 8,000 females. [1]
Fragile X syndrome in paediatric and adolescent patients
Transdermal