Presentation: Clinical evidence and access for medicinal cannabis products

TGA presentations given at: RACGP (GP17) conference, 26-28 October 2017

13 November 2017

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Presentation

  • Presented by: Dr Tony Gill
  • Presented at: GP17 RACGP Conference
  • Presentation date: 28 October 2017
  • Presentation summary: Overview of clinical evidence and access for medicinal cannabis products

Transcript

Notifications to prescription medicines

Dr Tony Gill
Pharmacovigilance and Special Access Branch
Therapeutic Goods Administration

GP17 RACGP Conference

Slide 1 - The government’s intent

  • Treat medicinal cannabis products as medicines
  • Provide patient access to Australian-grown and manufactured medicinal cannabis outside the standard registered medicines route
  • Provision of a quality medicine through doctors prescription
  • Encourage clinical trialling for potential future TGA registration
  • The Health Products Regulation Group has oversight
    • Cultivation and manufacture (Office of Drug Control)
    • Product GMP, product scheduling and patient access through the Therapeutic Goods Administration (TGA)
  • States and Territories also have a role in regulation

Slide 2 - Evidence

Whiting et al 2015

  • There was moderate quality evidence to support the use of cannabinoids for the treatment of:
    • chronic pain and
    • spasticity
  • There was low quality evidence suggesting that cannabinoids were associated with:
    • improvements in nausea and vomiting due to chemotherapy
    • weight gain in HIV infection
    • sleep disorders, and
    • Tourette syndrome
  • Cannabinoids were associated with an increased risk of short-term AEs

Slide 3 - Evidence

National Academy of Science 2017 Report

  • In adults with chemotherapy induced nausea and vomiting, oral cannabinoids are effective anti-emetics.
  • In adults with chronic pain, patients who were treated with cannabis or cannabinoids are more likely to experience a clinically significant reduction in pain symptoms
  • In adults with multiple sclerosis (MS) related spasticity, short-term use of oral cannabinoids improves patient-reported spasticity symptoms.
  • For these conditions the effects of cannabinoids are modest; for all other conditions evaluated there is inadequate information to assess their effects.

Slide 4 - Clinical evidence reviews

  • Conducted by team from U NSW, U Sydney, U QLD and collaborators
  • Focus on epilepsy, MS, pain types, nausea and vomiting and palliative care
  • Systematic reviews of published reviews and findings of individual studies using Medline, Embase, PsycINFO, and EBM Reviews
  • Studies published from 1980 to early 2017
  • Priority was given to RCTs but also included observational studies, e.g. case reports, retrospective chart reviews, self-report surveys
  • Anticipated that these reviews will be published in the next few months in international journals – currently being reviewed

Slide 5 - Epilepsy

  • Five RCTs and 17 observational studies were identified - all examined CBD as adjuvant treatment (in addition to standard antiepileptic drugs)
  • Randomised controlled studies
    • In patients with paediatric-onset drug-resistant epilepsy CBD products reduced seizure frequency and achieved seizure freedom compared with placebo
    • 14% of patients withdrew because of treatment-related adverse events
    • Doses of cannabidiol required were reasonably high (20mg/kg/day) and some uncertainty around contribution of the effect of CBD on clobazam metabolism
  • Observational studies
    • In 14 of 17 studies, 56% of patients reported reductions in seizures of 50% or more.
    • In 7 paediatric studies 13% were estimated to be seizure-free
    • 10 studies reported improved quality of life in paediatric and adult groups

Slide 6 - Cancer and HIV induced nausea and vomiting

  • 11 met inclusion criteria, but were mainly against old medicines
  • In managing CINV in adults, THC/ analogues were more effective than placebo, and as effective prochlorperazine at completely controlling nausea and vomiting, and controlling /reducing nausea
  • Comparison of cannabinoids against newer anti-emetics is required
  • Research on cannabinoids for CINV in children is more limited
  • Evidence of efficacy of cannabinoids in treating nausea and vomiting in late stage AIDS and terminal cancer was equivocal

Slide 7 - Palliative care

  • 9 double blind or open label RCTs studies with a total of 1561 participants were included, but evidence was low quality
  • In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake, appetite, nausea/vomiting, pain, dizziness, mental health or sleep problems
  • In HIV patients, cannabinoids were superior to placebo for weight gain and appetite but not for nausea/vomiting
  • No convincing evidence suggesting that cannabinoids are of value for anorexia or cachexia (weakness and wasting) in cancer or HIV

Slide 8 - Multiple sclerosis

  • Nabiximols are TGA approved for the use in MS for muscle spasticity.
  • 11 systematic reviews with data from 32 studies with 3146 patients.
  • These included 10 moderate/high-quality RCTs, that examined if cannabinoids reduced pain and spasticity.
  • Five reviews concluded that there was evidence that cannabinoids may be effective for symptoms of pain and/or spasticity and positive effects on sleep and bladder symptoms
  • Mixed findings were reported on quality of life, ataxia/tremor and disability/disease progression
  • A lack of studies with non-cannabinoid comparators is a is a major evidence gap

Slide 9 - Chronic non-cancer pain

  • 102 trials of all types of study designs considered
  • Most studies with nabiximols, THC/ analogues, THC-rich preparations
  • Most evidence on cannabinoids was from studies where cannabinoids were adjuvant interventions and not first line treatments for pain
  • Patients who had cannabinoids for MS-related neuropathic pain were more likely to experience a 30% reduction in pain (low confidence) and decrease in pain scores (moderate confidence)
  • patients who had cannabinoids for non-MS related neuropathic pain were more likely to experience a 50% reduction in pain and a reduction in pain scores
  • Insufficient information to make a conclusion about cannabinoids for the treatment of pain associated with arthritis and fibromyalgia

Slide 10 - Draft clinical guidance documents

  • Draft “clinical guidance documents” for the use of cannabinoids are being developed for epilepsy, MS, pain types, nausea and vomiting and palliative care
  • Decisions on patient access to particular cannabis products will be made by the treating physician with clinical oversight from the state/territory health departments and TGA
  • Aim to produce documents by end 2017 with input by Australian clinical experts and patient

Slide 11 - Flowchart

Flowchart illustrating the TGA, states and territories pathway for Patient to access to cannabis from manufacture to cultivation and production

Slide 12 - Individual importation of medicinal cannabis

Medical practitioners can arrange patient by patient importation to fill prescriptions issued using TGA SAS A

  • Requires a licence under the Customs (Prohibited Import) Regulations 1956

Individual patients can utilise travellers’ exemption

  • to carry up to 3 months supply of medicines with them on a ship or aeroplane entering into Australia with a valid doctor’s prescription
  • Prior State Health Department approval may also be required

Slide 13 - Medicinal cannabis products are available through “unapproved products” pathways

  • No ARTG product available (SATIVEX® is approved but Australian product is not being supplied currently)
  • Authorised prescriber
  • SAS A - notification pathway for patients who are seriously ill with a condition from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of early treatment
  • SAS B - application pathway for patients that do not fit SAS A

For help 1800 220 007/ 02 6232 8866, medicinal.cannabis@health.gov.au

Access to medicinal cannabis products: steps to using access schemes
(URL: https://www.tga.gov.au/access-medicinal-cannabis-products-steps-using-access-schemes)

Slide 14 - SAS B and Authorised Prescriber

Criteria depend upon the patients, product, prescriber

Authorised Prescribers must:

  • have training and expertise appropriate for the condition and the proposed use of the product, and
  • be able to best determine the needs of the patient and to monitor the outcome of therapy

Patient and clinical justification

  • patient information, diagnosis and indication treated
  • the seriousness of the condition
  • details of past treatment
  • expected benefits from the use of the product

Slide 15 - Product details

  • Trade name - Manufacturer/Company/Supplier
  • Dose Form i.e. tablet, extract and active ingredients
  • Shelf-life and Storage Conditions
  • Compliance with TGO 93 for composition / contamination

Administration details

  • Dosage, Route of administration, Duration of treatment

Monitoring Detail:

  • Efficacy of the treatment, adverse events/reactions
  • Human studies to demonstrate efficacy and safety data
  • Evidence levels depend on seriousness of the condition

Slide 16 - Notifications (SAS A) and Applications (SAS B and AP) 1 January 2016 to 10 October 2017

SAS A Notifications

  • 5 since June 2017 disallowance

SAS B Applications

  • Approved applications -173 (rest pending further information or withdrawn)
  • 74 for cannabidiol, rest for THC/ CBD in various ratios
  • Range of dosage forms for products

Authorised Prescriber Applications

  • Approved – 27 (and pending – 6) (101 patients to June 2017)

Slide 17 – Questions?

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