[go: up one dir, main page]

WO2022017961A1 - Utilisation du cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques - Google Patents

Utilisation du cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques Download PDF

Info

Publication number
WO2022017961A1
WO2022017961A1 PCT/EP2021/069903 EP2021069903W WO2022017961A1 WO 2022017961 A1 WO2022017961 A1 WO 2022017961A1 EP 2021069903 W EP2021069903 W EP 2021069903W WO 2022017961 A1 WO2022017961 A1 WO 2022017961A1
Authority
WO
WIPO (PCT)
Prior art keywords
cbd
preparation
seizures
thc
cannabinoids
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2021/069903
Other languages
English (en)
Inventor
Daniel Adam CHECKETTS
Kevin James CRAIG
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GW Research Ltd
Original Assignee
GW Research Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GW Research Ltd filed Critical GW Research Ltd
Publication of WO2022017961A1 publication Critical patent/WO2022017961A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants

Definitions

  • the present invention relates to the use of cannabidiol (CBD) for the treatment of seizures associated with rare epilepsy syndromes.
  • CBD cannabidiol
  • the seizures associated with rare epilepsy syndromes that are treated are those which are experienced in patients with trisomy 21.
  • the types of seizures include tonic and atonic seizures and spasms.
  • the dose of CBD is between 5 mg/kg/day to 50 mg/kg/day.
  • the CBD used is in the form of a highly purified extract of cannabis such that the CBD is present at greater than 95% of the total extract (w/w) and the cannabinoid tetrahydrocannabinol (THC) has been substantially removed, to a level of not more than 0.15% (w/w).
  • the CBD used is in the form of a botanically derived purified CBD which comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids. More preferably the other cannabinoids present are THC at a concentration of less than or equal to 0.1% (w/w); CBD-C1 at a concentration of less than or equal to 0.15% (w/w); CBDV at a concentration of less than or equal to 0.8% (w/w); and CBD-C4 at a concentration of less than or equal to 0.4% (w/w).
  • the botanically derived purified CBD preferably also comprises a mixture of both trans-THC and cis-THC. Alternatively, a synthetically produced CBD is used.
  • the other cannabinoids present are THC at a concentration of about 0.01% to about 0.1% (w/w); CBD-C1 at a concentration of about 0.1% to about 0.15% (w/w); CBDV at a concentration of about 0.2% to about 0.8% (w/w); and CBD-C4 at a concentration of about 0.3% to about 0.4% (w/w).
  • THC is present at a concentration of about 0.02% to about 0.05% (w/w).
  • the CBD may be formulated for administration separately, sequentially or simultaneously with one or more AED or the combination may be provided in a single dosage form.
  • Epilepsy occurs in approximately 1% of the population worldwide, (Thurman et ai, 2011) of which 70% are able to adequately control their symptoms with the available existing anti-epileptic drugs (AED). However, 30% of this patient group, (Eadie et al., 2012), are unable to obtain seizure freedom from the AED that are available and as such are termed as suffering from intractable or “treatment-resistant epilepsy” (TRE).
  • TRE treatment-resistant epilepsy
  • Intractable or treatment-resistant epilepsy was defined in 2009 by the International League against Epilepsy (I LAE) as “failure of adequate trials of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom ” (Kwan et al., 2009).
  • Childhood epilepsy is a relatively common neurological disorder in children and young adults with a prevalence of approximately 700 per 100,000. This is twice the number of epileptic adults per population.
  • the main symptom of epilepsy is repeated seizures.
  • Clinical observations and electroencephalography (EEG) tests are conducted and the type(s) of seizures are classified according to the ILEA classification.
  • Generalized seizures where the seizure arises within and rapidly engages bilaterally distributed networks, can be split into six subtypes: tonic-clonic (grand mal) seizures; absence (petit mal) seizures; clonic seizures; tonic seizures; atonic seizures and myoclonic seizures.
  • Focal (partial) seizures where the seizure originates within networks limited to only one hemisphere, are also split into sub-categories.
  • the seizure is characterized according to one or more features of the seizure, including aura, motor, autonomic and awareness / responsiveness.
  • a seizure begins as a localized seizure and rapidly evolves to be distributed within bilateral networks this seizure is known as a bilateral convulsive seizure, which is the proposed terminology to replace secondary generalized seizures (generalized seizures that have evolved from focal seizures and are no longer remain localized).
  • Trisomy 21 occurs when a person has three copies of chromosome 21 instead of the normal two. This gross chromosomal abnormality causes a condition called Down syndrome and is typically not inherited. Down syndrome may be caused by three possible genetic causes: trisomy 21 is caused by an extra chromosome 21 in all cells of the person; mosaic trisomy 21 is when only some cells in have an extra copy; and translocation trisomy 21 is when extra chromosome 21 material translocates onto another chromosome.
  • Down syndrome is associated with varying degree of intellectual disability, a characteristic facial appearance, a small nose, an upward slant to the eyes, a short stature, low muscle tone in infancy and a single deep crease across the center of the palm. Other symptoms of the syndrome may include heart defects, digestive abnormalities, gastroesophageal reflux, celiac disease, hypothyroidism, hearing and vision problems, leukemia, and Alzheimer disease. [0017] Down syndrome has a better prognosis in comparison to most other disorders caused by an extra chromosome. The aging process is accelerated, but most children with Down syndrome survive to adulthood and the average life expectancy is 55 years.
  • Treatment focuses on the specific symptoms in each person.
  • the overall goal of treatment is to boost cognition by improving learning, memory, and speech.
  • Early intervention services, educational programs, a supportive home environment and good health care can all help achieve this.
  • CBD Cannabidiol
  • a report from a website supporting those affected by childhood brain injury discusses the different aspects of a child’s recovery program including the use of CBD oil to treat seizures afflicting children with Down syndrome. 1 However, there is no indication of the types of seizures that would be reduced nor the dose or composition of CBD that would be used.
  • GB 2531282 discloses the effectiveness of highly purified CBD in the treatment of atonic seizures associated with Lennox-Gastaut Syndrome. However, there is no data of patients with trisomy 21 nor is there any mention of these conditions. [0024] The applicant has found by way of an open label, expanded-access program that treatment with CBD resulted in a significant reduction in tonic and atonic seizures and spasms in patients with trisomy 21.
  • CBD cannabidiol
  • the seizures associated with trisomy 21 are tonic and atonic seizures and spasms.
  • the CBD preparation comprises greater than 95% (w/w) CBD and not more than 0.15% (w/w) tetrahydrocannabinol (THC).
  • the CBD preparation comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids, wherein the less than or equal to 2% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); cannabidiol- C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4), and wherein the THC is present as a mixture of trans-THC and cis-THC.
  • THC cannabinoids tetrahydrocannabinol
  • CBD-C1 cannabidiol- C1
  • CBDDV cannabidivarin
  • CBD-C4 cannabidiol-C4
  • the CBD preparation is used in combination with one or more concomitant anti-epileptic drugs (AED).
  • AED concomitant anti-epileptic drugs
  • the one or more AED is selected from the group consisting of: levetiracetam, clobazam, vigabatrin, rufinamide, lacosamide and felbamate.
  • the CBD is present is isolated from cannabis plant material.
  • the CBD is present as a synthetic preparation.
  • the dose of CBD is greater than 5 mg/kg/day. More preferably the dose of CBD is 20 mg/kg/day. More preferably the dose of CBD is 25 mg/kg/day. More preferably the dose of CBD is 50 mg/kg/day.
  • a method of treating seizures associated with trisomy 21 comprising administering a cannabidiol (CBD) preparation to the subject in need thereof.
  • CBD cannabidiol
  • cannabinoids Over 100 different cannabinoids have been identified, see for example, Handbook of Cannabis, Roger Pertwee, Chapter 1, pages 3 to 15. These cannabinoids can be split into different groups as follows: Phytocannabinoids; Endocannabinoids and Synthetic cannabinoids (which may be novel cannabinoids or synthetically produced phytocannabinoids or endocannabinoids).
  • phytocannabinoids are cannabinoids that originate from nature and can be found in the cannabis plant.
  • the phytocannabinoids can be isolated from plants to produce a highly purified extract or can be reproduced synthetically.
  • “Highly purified cannabinoids” are defined as cannabinoids that have been extracted from the cannabis plant and purified to the extent that other cannabinoids and non-cannabinoid components that are co-extracted with the cannabinoids have been removed, such that the highly purified cannabinoid is greater than or equal to 95% (w/w) pure.
  • Synthetic cannabinoids are compounds that have a cannabinoid or cannabinoid-like structure and are manufactured using chemical means rather than by the plant.
  • Phytocannabinoids can be obtained as either the neutral (decarboxylated form) or the carboxylic acid form depending on the method used to extract the cannabinoids. For example, it is known that heating the carboxylic acid form will cause most of the carboxylic acid form to decarboxylate into the neutral form.
  • Treatment-resistant epilepsy (TRE) or “intractable epilepsy” is defined as per the I LAE guidance of 2009 as epilepsy that is not adequately controlled by trials of one or more AED.
  • Tonic seizures can be generalised onset, affecting both sides of the brain, or they can be focal onset, starting in just one side of the brain. If a tonic seizure starts in both sides of the brain, all muscles tighten and the subject’s body goes stiff. If standing, they may fall to the floor, their neck may extend, eyes open wide and roll upwards, whilst their arms may raise upwards and legs stretch or contract. If a tonic seizure starts in one side of the brain muscles tighten in just one area of the body. Tonic seizures usually last less than one minute.
  • Atonic seizures occur when a person suddenly loses muscle tone so their head or body may go limp. They are also known as drop attacks. In some children, only their head drops suddenly. They can begin in one area or side of the brain (focal onset) or both sides of the brain (generalized onset).
  • Epileptic spasm “infantile spasm”, “juvenile spasm” or “West syndrome” is defined as sudden flexion, extension or mixed flexion-extension of proximal and truncal muscles, lasting 1- 2 seconds. Spasms typically occur in a series, usually on wakening. Subtle forms may occur with only chin movement, grimacing, or head nodding. Spasms may be bilaterally symmetric, asymmetric, or unilateral, depending on whether they are generalised onset or focal onset.
  • the drug substance used is a liquid carbon dioxide extract of high-CBD containing chemotypes of Cannabis sativa L. which had been further purified by a solvent crystallization method to yield CBD.
  • the crystallisation process specifically removes other cannabinoids and plant components to yield greater than 95% CBD.
  • CBD is highly purified because it is produced from a cannabis plant rather than synthetically there is a small number of other cannabinoids which are co-produced and co-extracted with the CBD. Details of these cannabinoids and the quantities in which they are present in the medication are as described in Table A below.
  • the drug substance used in the trials is a liquid carbon dioxide extract of high-CBD containing chemotypes of Cannabis sativa L. which had been further purified by a solvent crystallization method to yield CBD.
  • the crystallisation process specifically removes other cannabinoids and plant components to yield greater than 95% CBD w/w, typically greater than 98% w/w.
  • the Cannabis sativa L. plants are grown, harvested, and processed to produce a botanical extract (intermediate) and then purified by crystallization to yield the CBD (botanically derived purified CBD).
  • the plant starting material is referred to as Botanical Raw Material (BRM); the botanical extract is the intermediate; and the active pharmaceutical ingredient (API) is CBD, the drug substance.
  • BRM Botanical Raw Material
  • API active pharmaceutical ingredient
  • the purity of the botanically derived purified CBD preparation was greater than or equal to 98%.
  • the botanically derived purified CBD includes THC and other cannabinoids, e.g., CBDA, CBDV, CBD-C1 , and CBD-C4.
  • the CBD preparation comprises not more than 0.15% THC based on total amount of cannabinoid in the preparation. In some embodiments, the CBD preparation comprises about 0.01% to about 0.1% THC based on total amount of cannabinoid in the preparation. In some embodiments, the CBD preparation comprises about 0.02% to about 0.05% THC based on total amount of cannabinoid in the preparation.
  • the CBD preparation comprises about 0.2% to about 1.0% CBDV based on total amount of cannabinoid in the preparation. In some embodiments, the CBD preparation comprises about 0.2% to about 0.8% CBDV based on total amount of cannabinoid in the preparation. [0055] In some embodiments, the CBD preparation comprises about 0.3% to about 0.5%
  • CBD-C4 based on total amount of cannabinoid in the preparation.
  • the CBD preparation comprises about 0.3% to about 0.4% CBD-C4 based on total amount of cannabinoid in the preparation.
  • the CBD preparation comprises about 0.1% to about 0.15% CBD-C1 based on total amount of cannabinoid in the preparation.
  • Distinct chemotypes of the Cannabis sativa L. plant have been produced to maximize the output of the specific chemical constituents, the cannabinoids. Certain chemovars produce predominantly CBD. Only the (-)-trans isomer of CBD is believed to occur naturally. During purification, the stereochemistry of CBD is not affected.
  • High CBD chemovars were grown, harvested, dried, baled and stored in a dry room until required.
  • the botanical raw material (BRM) was finely chopped using an Apex mill fitted with a 1 mm screen. The milled BRM was stored in a freezer prior to extraction.
  • the BDS produced using the methodology above was dispersed in C 5 -C 12 straight chain or branched alkane.
  • the mixture was manually agitated to break up any lumps and the sealed container then placed in a freezer for approximately 48 hours.
  • the crystals were isolated via vacuum filtration, washed with aliquots of cold C 5 -C 12 straight chain or branched alkane, and dried under a vacuum of ⁇ 10mb at a temperature of 60°C until dry.
  • the botanically derived purified CBD preparation was stored in a freezer at -20°C in a pharmaceutical grade stainless steel container, with FDA food grade approved silicone seal and clamps.
  • the botanically derived purified CBD used in the clinical trial described in the invention comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids.
  • the other cannabinoids present are THC at a concentration of less than or equal to 0.1% (w/w); CBD-C1 at a concentration of less than or equal to 0.15% (w/w); CBDV at a concentration of less than or equal to 0.8% (w/w); and CBD-C4 at a concentration of less than or equal to 0.4% (w/w).
  • the botanically derived purified CBD used additionally comprises a mixture of both trans-THC and cis-THC. It was found that the ratio of the trans-THC to cis-THC is altered and can be controlled by the processing and purification process, ranging from 3.3:1 (trans-THC:cis- THC) in its unrefined decarboxylated state to 0.8:1 (trans-THC:cis-THC) when highly purified. [0066] Furthermore, the cis-THC found in botanically derived purified CBD is present as a mixture of both the (+)-cis-THC and the (-)-cis-THC isoforms.
  • CBD preparation could be produced synthetically by producing a composition with duplicate components.
  • Example 1 describes the use of a botanically derived purified CBD in an open label, expanded-access program to investigate the clinical efficacy and safety of purified pharmaceutical cannabidiol formulation (CBD) in the treatment of seizures associated with trisomy 21.
  • CBD cannabidiol formulation
  • Subjects were required to be on one or more AEDs at stable doses for a minimum of two weeks prior to baseline and to have stable vagus nerve stimulation (VNS) settings and ketogenic diet ratios for a minimum of four weeks prior to baseline.
  • VNS vagus nerve stimulation
  • Patients were administered botanically derived purified CBD in a 100 mg/mL sesame oil- based solution.
  • a maximum dose of 50 mg/kg/day could be utilised for patients who were tolerating the medication but had not achieved seizure control; these patients had further weekly titration by 5mg/kg/day.
  • Seizure frequency, intensity, and duration were recorded by caregivers in a diary during a baseline period of at least 28 days. Changes in seizure frequency relative to baseline were calculated after at least 2 weeks and at defined timepoints of treatment.
  • Patients may be defined as responders if they had more than 50% reduction in seizure frequency compared to baseline.
  • the percent change in seizure frequency was calculated as follows: frequency
  • the percent change of seizure frequency may be calculated for any time interval where seizure number has been recorded.
  • the percent change of seizure frequency for the end of the treatment period was calculated as follows:
  • Table 1 Patient demographics, seizure type and concomitant medication
  • LEV levetiracetam
  • CLB clobazam
  • VGB vigabatrin
  • RFN rufinamide
  • LCS lacosamide
  • FLB felbamate
  • Tables 2A-C illustrate the seizure frequency for each patient as well as the dose of CBD given.
  • Table 2A Seizure frequency data for Patient 1
  • Patient 3 was treated for 8 weeks and did not experience a reduction in seizures over the treatment period.
  • this study signifies the use of CBD for treatment of seizures associated with trisomy 21.
  • Seizure types include tonic and atonic seizures and spasms for which seizure frequency rates decreased by significant rates, by 20-75%.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne l'utilisation du cannabidiol (CBD) pour le traitement de crises associées à des syndromes épileptiques rares. En particulier, les crises associées à des syndromes épileptiques rares qui sont traitées sont celles qui sont rencontrées chez des patients atteints de trisomie 21. Dans un autre mode de réalisation, les types de crises comprennent les crises toniques et atoniques ainsi que les spasmes. De préférence, la dose de CBD est comprise entre 5 mg/kg/jour et 50 mg/kg/jour.
PCT/EP2021/069903 2020-07-20 2021-07-15 Utilisation du cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques Ceased WO2022017961A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB2011158.9A GB2597310A (en) 2020-07-20 2020-07-20 Use of cannabidiol in the treatment of seizures associated with rare epilepsy syndromes related to genetic abnormalities
GB2011158.9 2020-07-20

Publications (1)

Publication Number Publication Date
WO2022017961A1 true WO2022017961A1 (fr) 2022-01-27

Family

ID=72338971

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2021/069903 Ceased WO2022017961A1 (fr) 2020-07-20 2021-07-15 Utilisation du cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques

Country Status (2)

Country Link
GB (1) GB2597310A (fr)
WO (1) WO2022017961A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2531282A (en) 2014-10-14 2016-04-20 Gw Pharma Ltd Use of cannabinoids in the treatment of epilepsy
WO2019207319A1 (fr) * 2018-04-27 2019-10-31 GW Research Limited Préparations de cannabidiol et leurs utilisations

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2531282A (en) 2014-10-14 2016-04-20 Gw Pharma Ltd Use of cannabinoids in the treatment of epilepsy
WO2019207319A1 (fr) * 2018-04-27 2019-10-31 GW Research Limited Préparations de cannabidiol et leurs utilisations

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CARABALLO ROBERTO ET AL: "Effectiveness of cannabidiol in a prospective cohort of children with drug-resistant epileptic encephalopathy in Argentina", SEIZURE, BAILLIERE TINDALL, LONDON, GB, vol. 80, 6 June 2020 (2020-06-06), pages 75 - 80, XP086246226, ISSN: 1059-1311, [retrieved on 20200606], DOI: 10.1016/J.SEIZURE.2020.06.005 *
DEVINSKY ORRIN ET AL: "Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial", LANCET NEUROLOGY, LANCET PUBLISHING GROUP, LONDON, GB, vol. 15, no. 3, 24 December 2015 (2015-12-24), pages 270 - 278, XP029415431, ISSN: 1474-4422, DOI: 10.1016/S1474-4422(15)00379-8 *
ROGER PERTWEE: "Handbook of Cannabis", pages: 3 - 15

Also Published As

Publication number Publication date
GB2597310A (en) 2022-01-26
GB202011158D0 (en) 2020-09-02

Similar Documents

Publication Publication Date Title
EP4181891B1 (fr) Utilisation du cannabidiol dans le traitement des crises d'absence associées aux syndromes d'épilepsie rares liés aux lésions cérébrales
AU2020279889A1 (en) Use of cannabidiol in the treatment of epileptic spasms
WO2022017942A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des mutations dans le gène syngap1
WO2022017962A1 (fr) Utilisation du cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
WO2022017945A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
WO2022017946A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
EP4181888A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau
EP4181902A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
WO2022017909A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes d'épilepsies rares associées à des anomalies structurales du cerveau
WO2022017947A1 (fr) Utilisation du cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
US20230285427A1 (en) Use of cannabidiol in the treatment of seizures associated with rett syndrome
WO2022017961A1 (fr) Utilisation du cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
WO2022017917A1 (fr) Cannabidiol destiné à être utilisé dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau
WO2022017944A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à une dégénérescence cérébrale bilatérale
WO2022017915A1 (fr) Cannabidiol destiné à être utilisé dans le traitement de crises associées à des lésions cérébrales
WO2022017951A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des troubles liés au gène cask
WO2022017913A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
WO2022017920A1 (fr) Cannabidiol destiné à être utilisé dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau
WO2022017936A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes d'épilepsies rares liés à des anomalies structurales du cerveau
WO2022017929A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à la lissencéphalie
WO2022017925A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées au syndrome épileptique multifocal
EP4181889A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes rares d'épilepsie liés à des anomalies génétiques
WO2022017954A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau
WO2022017953A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
GB2597278A (en) Use of cannabidiol in the treatment of seizures associated with rare epilepsy syndromes related to structural abnormalities of the brain

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21745992

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21745992

Country of ref document: EP

Kind code of ref document: A1