Public Assessment Report - GOV.UK

1 DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. Public Assessment Report Decentralised Procedure Sativex Oromucosal Spray UK/H/2462/001/DC. UK licence no: PL 18024/0009. GW Pharma Limited 1. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. LAY SUMMARY. The MHRA granted GW Pharma Limited a Marketing Authorisation (licence) for the medicinal product Sativex Oromucosal Spray (PL 18024/0009) on 16th June 2010. This is a prescription- only medicine (POM) used to improve symptoms related to muscle stiffness (spasticity) in multiple sclerosis (MS). Health professionals sometimes talk about spasticity' when describing the muscle stiffness. Spasticity means there is an increase in muscle tone'. In other words, when the muscle is moved, there is more resistance to this movement than there normally would be. Muscles feel more rigid.

2 Sativex is used when other medicines have not worked to relieve your muscle stiffness. Sativex is a mouth spray which contains cannabis extracts containing compounds called cannabinoids. No new or unexpected safety concerns arose from these applications and it was, therefore, judged that the benefits of taking Sativex Oromucosal Spray outweigh the risks, hence Marketing Authorisations have been granted. 2. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. TABLE OF CONTENTS. Module 1: Information about initial procedure Page 4. Module 2: Summary of Product Characteristics Page 5. Module 3: Product Information Leaflets Page 6. Module 4: Labelling Page 7. Module 5: Scientific Discussion Page 9. 1 Introduction 2 Quality aspects 3 Non-clinical aspects 4 Clinical aspects 5 List of outstanding issues Module 6 Steps taken after Assessment Page 112.

3 Variation Assessment Report Annex 1 Page 113. 3. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. Module 1. Information about the initial procedure Proposed name of the medicinal Sativex Oromucosal Spray product in the RMS. INN (or common name) of the Delta-9-tetrahydrocannabinol Botanical Drug active substance(s): Substance (THC BDS) [Tetranabinex] and Cannabidiol Botanical Drug Substance (CBD BDS). [Nabidiolex], as extract of Cannabis sativa L. ATC Code N02BG 10. Pharmaceutical form(s) and Oromucosal Spray strength(s): Reference Number for the UK/H/2462/001/DC. Decentralised Procedure Reference Member State: United Kingdom Member States concerned: Spain Applicant (name and address) GW Pharma Limited Porton Down Science Park, Salisbury, Wiltshire SP4 OJQ. Timetable Day 210 17th May 2010. 4. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC.

4 Module 2. Summary of Product Characteristics In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPCs) for products granted Marketing Authorisations at a national level are available on the MHRA website. 5. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. Module 3. Patient Information Leaflet In accordance with Directive 2010/84/EU the Patient Information Leaflets (PILs) for products granted Marketing Authorisations at anational level are available on the MHRA website. 6. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. Module 4. Labelling 7. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. 8. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. Module 5. Scientific discussion during initial procedure I INTRODUCTION. Based on the review of the data on quality, safety and efficacy, the member states considered that the application for Sativex Oromucosal Spray (PL 18024/0009; UK/H/2462/001/DC) could be approved.

5 This application was submitted by the decentralised procedure, with the UK as reference member state (RMS) and Spain as concerned member state (CMS). The product is a prescription-only medicine as add-on treatment, for symptom improvement in patients with moderate to severe spasticity due to multiple sclerosis (MS) who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy. These are applications made under the decentralised procedure (DCP), according to Article of 2001/83/EC, as amended, for a new active substance Delta-9-tetrahydrocannabinol Botanical Drug Substance (THC BDS) with Cannabidiol Botanical Drug Substance (CBD BDS). The product is a solution for use as an oromucosal spray containing a combination of two extracts from Cannabis sativa L, equivalent to 27mg/ml delta-9-tetrahydrocannabinol and 25mg/ml cannabidiol.

6 Beneficial effects of cannabis on symptoms such as pain, urinary disturbance, tremor, spasm and spasiticity have also been claimed by individuals with multiple sclerosis (MS). A previous application for this product was submitted in 2006 via the decentralised procedure (UK/H/961/01/DC). The Concerned Member States for this earlier procedure were DK, ES and NL. That application was withdrawn by the Applicant following the Day 180 Draft Assessment Report . At the time of the withdrawal of the application the RMS (UK) and CMSs unanimously considered that the application for Sativex Oromucosal Spray as add-on therapy, for symptomatic relief of spasticity in patients with multiple sclerosis (MS) was not approvable. Further information on the previous application can be found in the Public Information Report at the following link which was published in December 2007.

7 In the current application, filed in May 2009, the applicant has provided substantial new data to address issues relating to efficacy that were identified in the earlier decentralised procedure. All non-clinical studies were conducted in accordance with current regulations. All clinical studies were conducted in accordance with Good Clinical Practice (GCP). The RMS has been assured that acceptable standards of GMP are in place for these product types at all sites responsible for the manufacture, assembly and batch release of these products. The RMS and CMS considered that the applications could be approved with the end of procedure (Day 210) on 17th May 2010. After a subsequent national phase, the licences were granted in the UK on 16th June 2010. 9. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. II. ABOUT THE PRODUCT.

8 Name of the product in the Sativex Oromucosal Spray Reference Member State Name(s) of the active substance(s) Delta-9-tetrahydrocannabinol Botanical Drug (INN) Substance (THC BDS) [Tetranabinex] and Cannabidiol Botanical Drug Substance (CBD. BDS) [Nabidiolex], as extracts of Cannabis sativa L. Pharmacotherapeutic classification NO2BG 10. (ATC code). Pharmaceutical form and 27mg/ml delta-9-tetrahydrocannabinol and strength(s) 25mg/ml cannabidol Reference numbers for the Mutual UK/H/2462/001/DC. Recognition Procedure Reference Member State United Kingdom Member States concerned Spain Marketing Authorisation Number(s) PL 18024/0009. Name and address of the GW Pharma Limited, Porton Down Science authorisation holder Park, Salisbury, Wiltshire, SP4 OJQ. 10. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. III SCIENTIFIC OVERVIEW AND DISCUSSION.

9 QUALITY ASPECTS. S. Active substances The two active substances are extracts from the leaves and flowers of the plant Cannabis sativa L., standardised to contain THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol), respectively. Common Name: Delta-9-tetrahydrocannabinol Chemical Name: ( )-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a ,7,8,10a-tetrahydro-6H- benzo[c]chromen-1-ol Molecular Formula: C21H30O2. Chemical Structure: Molecular Weight: Common Name: Cannabidiol Chemical Name: 2-[(1R,6R)-6-isopropenyl-3-methylcyclohe x-2-en-1-yl]-5-pentylbenzene- 1,3-diol Molecular Formula: C21H30O2. Chemical Structure: Molecular Weight: Herbal substances The plants are cultivated in line with Good Agricultural and Collection Practice (GACP). Two plant varieties are grown; one that contains higher levels of THC (delta-9-tetrahydrocannabinol).

10 And one that contains higher levels of CBD (cannabidiol). Satisfactory details have been provided describing the production of the herbal substances. Appropriate specifications have been provided for both herbal substances. Analytical methods have been appropriately validated and are satisfactory for ensuring compliance with the relevant specifications. Batch analysis data are provided and comply with the proposed specifications. 11. DCPAR Sativex Or omucosal Spr ay UK/H/2462/001/DC. Appropriate stability data have been provided and support the proposed retest period Herbal preparations Preparation of the extracts from the herbal substances has been adequately described, and appropriate in-process controls and intermediate specifications are applied. Satisfactory specification tests are in place for all starting materials and reagents, and these are supported by relevant certificates of analysis.