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Cannabidiol oil - potential adverse effects

27 February 2020Self-administration of over-the-counter bought CBD is increasingly popular and doctors and pharmacists should be aware of its potential adverse effects. The Food Standards Agency (FSA)…

Assessing the quality of Cannabis-Based Products for Medicinal Use (CBPM) and cannabis-based food supplements available in the UK (January 2020): NHS Pharmaceutical QA Committee

15 January 2020This document has been written to inform purchasing decisions and other professional judgements which pharmacists may need to make when supporting the care of patients…
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New Medicines

Epidyolex (EU), Epidiolex (US)Tuberous sclerosis complex in adults and children - add-on therapy for inadequately-controlled seizures

Information

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

Development and Regulatory status

Launched
Launched
Launched
August 2021
Yes
Yes
Aug 21Licence extension approved by MHRA. New indication is use as adjunctive therapy of seizures associated with tuberous sclerosis complex (TSC) for patients 2 years of age and older [16].
Apr 21Licence extension approved in EU [15].
Feb 21Recommended for EU approval by CHMP - the additional indication is "for use as adjunctive therapy of seizures associated with tuberous sclerosis complex (TSC) for patients 2 years of age and older" [14].
Jul 20Licence change approved in US for the treatment of seizures associated with tuberous sclerosis complex (TSC) in patients one year of age and older [12].
Mar 20Filed in EU; filed in US in February 2020 [11].
Nov 19TSC PIII data to be presented at American Epilepsy Society annual meeting in Dec 19. Following that, GW expects to file a sNDA with the FDA in early 2020 (approval decision expected mid-20) and file to the EMA in Q1 20 [10].
May 19Following announcement that a PIII trial has met its primary outcome, GW Pharma plans to file in the US in Q4 19. No details on plans for EU filing but presumably will follow [8].
Feb 18Granted orphan drug status in EU for treatment of TSC [5].
Apr 16Granted orphan drug status in US for treatment of Tuberous Sclerosis Complex [3].
Apr 15GW Pharmaceuticals plc announced new physician reports of clinical effect and safety associated with the Epidiolex® expanded access program. These data were presented at the American Academy of Neurology annual meeting in Washington DC. Based on the findings in the expanded access program, GW has continued to explore options to commence clinical development of Epidiolex in an additional pediatric epilepsy indication. GW has now concluded that this additional target indication should be Tuberous Sclerosis Complex (TSC) and expects to commence clinical development in TSC later this year [1].

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].
Tuberous sclerosis complex in adults and children - add-on therapy for inadequately-controlled seizures
Oral

Further information

Yes

Trial or other data

Dec 20PIII RCT (NCT02544763; n=224) reports cannabidiol significantly reduced tuberous sclerosis complex -associated seizures from baseline vs. placebo; reduction of 48.6% for the 25mg group, 47.5% for 50mg group vs. 26.5% for placebo; and 25mg/kg/day dose had better safety profile vs. 50-mg/kg/day [13].
May 19In the PIII trial, epidiolex reduced TSC-associated seizures, which include both focal and generalised seizures types. Epidiolex hit the primary endpoint (reduction in seizure frequency vs. baseline) in the trial. Epidiolex 25 mg and 50 mg both provided seizure reductions of 49% and 48% from baseline respectively in comparison to 27% for placebo. All secondary endpoints supported the primary endpoint and the safety profile of Epidiolex remained consistent. The most common adverse events with epidiolex included somnolence, decreased appetite, diarrhea, constipation, vomiting, transaminase elevations, pyrexia, seizure, cough and infections.[7]
Sep 18PIII (NCT02544763) study has finished recruitment and expects to complete collection of primary outcome data in Feb 19. In PIII study (NCT02544750), primary outcome data collection will complete Feb 22 [4].
Oct 17PIII (NCT02544763) study is still recruiting patients and expects to complete collection of primary outcome data in Sep 18. PIII (NCT02544750) is enrolling by invitation and primary outcome data collection will complete Sep 20 [4].
Apr 16GW Research has started the first of two PIII trials to evaluate the efficacy and safety of cannabidiol as add-on therapy in patients with tuberous sclerosis complex who experience inadequately-controlled focal seizures (GWEP1521 Blinded Phase; EudraCT2015-002154-12; NCT02544763)(GWEP1521 Open-Label Extension; EudraCT2015-002154-12; NCT02544750). Each of the trials consists of two parts, the first being a double-blind phase and the second being an open-label extension phase. The randomised, open-label, single-group assignment trials will enrol 144 patients (≥2 years and ≤65 years) in the US, UK and France [1].

Evidence based evaluations

Zygel Fragile X syndrome in paediatric and adolescent patients with complete methylation

Information

Zygel
New formulation - repurposed medicine
Zynerba Pharmaceuticals
Zynerba Pharmaceuticals

Development and Regulatory status

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

Category

Cannabinoid receptor CB1 antagonist.
Rare genetic developmental disability, affecting ~1 in 4,000 males and 1 in 6,000 to 8,000 females [1]. A mutation impacts the FMR1 gene and causes endocannabinoid system dysregulation, causing core cognitive, social and behavioral symptoms. The mutation manifests as multiple CGG repeats in FMR1 (full mutation = >200 repeats). Methylation of FMR1 also plays a role in determining functionality of the gene; ~60% of patients are believed to fall into the completely methylated category [17].
Fragile X syndrome in paediatric and adolescent patients with complete methylation
Transdermal