Eslicarbazepine Acetate

The PBAC did not recommend the listing of eslicarbazepine acetate (ESL) for the treatment of intractable partial epileptic seizures, with or without secondary generalised seizures. The PBAC considered that the efficacy of ESL compared to placebo in a treatment-resistant population, and the claim of non-inferior effectiveness and safety of ESL compared with lacosamide (LAC), were not supported by the clinical data and indirect treatment comparison (ITC).PSD · Mar 2021

Like carbamazepine and oxcarbazepine, the PBAC noted that ESL is a member of the dibenzazepine family (the carboxamides), with similar potential side effects. If ESL were used third-line, the PBAC considered that it may be a less attractive option for clinicians in an adjuvant setting compared to an agent from a novel therapeutic class (e.g. LAC), and that LAC may not be the therapy that is replaced.PSD · Mar 2021

The submission estimated that ESL 800 mg daily is equi-effective to LAC 200 mg daily (4:1), and ESL 1,200 mg daily is equi-effective to LAC 400 mg daily (3:1), based on the recommended doses used in the trials and the respective Australian PI. The submission applied the dosage proportions of LAC utilisation to calculate the split between the ESL 800 mg and 1,200 mg doses.PSD · Mar 2021

The submission claimed that the proposed equi-effective doses are valid because they are trial-based; however, the ESL dose was allocated to patients on trial entry, and therefore does not apply to clinical practice. The sponsor did not provide further analysis of the actual doses received in the clinical trials (e.g. mean dosage used, treatment duration etc). The ESC noted that real-world data from Villaneuva et al.PSD · Mar 2021

The submission described ESL (both 800 mg and 1,200 mg doses) as non-inferior in terms of effectiveness and safety compared with LAC in the third-line treatment of treatment-resistant POS. This claim was not supported by the evidence submitted. The key issues were:PSD · Mar 2021

The proposed line of therapy and comparator was inappropriate, and ESL is unlikely to displace LAC (paragraph 5.3). The ESC considered there was no evidence that ESL would confer any substantial benefit to any subgroup of patients with medically refractory epilepsy in the third-line setting; after having tried and failed another dibenzazepine clinicians may be unlikely to forgo the opportunity to add a drug with a novel mechanism of action.PSD · Mar 2021

The submission did not provide details of a risk sharing arrangement (RSA). There is a RSA in place for the nominated comparator, lacosamide, in conjunction with brivaracetam and perampanel for the treatment of intractable partial epileptic seizures. The pre-PBAC response stated that the sponsor would be agreeable to joining the RSA, pending the Department providing the details of the agreement. 20PSD · Mar 2021