EPIDYOLEX 100 mg/ml (cannabidiol)

Key points

Favourable opinion for reimbursement as adjunctive therapy of seizures associated with tuberous sclerosis complex (TSC) for patients 2 years of age and older only in the event of drug-resistant epilepsy.

Unfavourable opinion for reimbursement as adjunctive therapy of seizures associated with tuberous sclerosis complex (TSC) for non-drug-resistant patients 2 years of age and older.

What therapeutic improvement?

No clinical added value as adjunctive therapy in the treatment of seizures associated with tuberous sclerosis complex for patients 2 years of age and older with drug-resistant epilepsy.

Role in the care pathway?

The guidelines recommend the following in patients with TSC presenting epileptic seizures:

• As first-line therapy: vigabatrin in patients under the age of 1 year, combined with another antiepileptic which increases GABAergic inhibition in those aged at least 1 year.
• As second-line therapy: surgery, the success of which depends on the precise location of the epileptic focus and the focal nature of the seizures, is recommended in children inadequately controlled with two antiepileptic drugs and with a single and identifiable epileptogenic focus. The success rate for surgery is between 25 and 90%.
• As third-line therapy: a ketogenic diet, vagus nerve stimulation and other antiepileptics used for focal seizures.

In patients aged at least 2 years VOTUBIA (everolimus) dispersible tablets can be used in combination with conventional antiepileptics, where the epilepsy becomes drug-resistant (i.e. after failure of 2 antiepileptics). It should be noted that in patients eligible for surgery, namely patients with a single and identifiable epileptogenic focus, VOTUBIA (everolimus) is not an alternative to surgery and its use must not delay a surgical decision.

Role of EPIDYOLEX (cannabidiol) in the care pathway:

In view of:

• demonstration of the efficacy of EPIDYOLEX (cannabidiol), compared to placebo, both as adjunctive therapy, only in terms of the total frequency of TSC-associated epileptic seizures in the short term (16 weeks) with a modest size effect,
• the absence of a demonstrated statistically significant reduction compared to placebo, both as adjunctive therapy, on the ranked secondary endpoint of responder rate (at least 50% reduction in the number of seizures),
• and in the absence of available data compared to another anti-epileptic drug in a context of a high level of drug resistance (89% receiving ≥ 2 AE),

the Committee considers that EPIDYOLEX (cannabidiol) is a treatment option in seizures associated with tuberous sclerosis complex for patients 2 years of age and older with drug-resistant epilepsy.

In the absence of comparative data between EPIDYOLEX (cannabidiol) and VOTUBIA (everolimus), in a context in which they were the subject of concomitant development, the choice between these two proprietary medicinal products should be made, in particular, on the basis of the patient’s characteristics, the efficacy of the medicinal products and their different safety profiles associated with contraindications.

The potential benefit of treatment with cannabidiol should be assessed taking into consideration the product’s safety and the absence of long-term safety data, in particular its hepatic safety (increased hepatic enzymes).

In the other situations of the MA indication extension, i.e. non-drug-resistant patients with TSC, given the limited data in this population, the Committee considers that EPIDYOLEX (cannabidiol) has no role in the treatment strategy.

 Special recommendations

The Committee points out that the multi-dose vial packaging with two dosing devices graduated in ml, whereas the dosage is expressed in mg, requires a conversion (from mg to ml), promoting the risk of medication errors and overdose. The Committee also highlights the importance of ensuring the dosage wording is clear on the medical prescription and providing adequate information to the persons responsible for dispensing and administering EPIDYOLEX (cannabidiol), including healthcare professionals and the child’s family.