MAVENCLAD

What it is

MAVENCLAD contains 10 mg cladribine per tablet. Cladribine is a nucleoside analogue of deoxyadenosine. A chlorine substitution in the purine ring protects cladribine from degradation by adenosine deaminase, increasing the intracellular residence time of the cladribine prodrug. Cladribine leads to selective depletion of dividing and non-dividing T and B cells.

Approved indications

— Relapsing-remitting multiple sclerosis (RRMS) to reduce the frequency of clinical relapses and to delay the progression of physical disability.

Dosing overview

The recommended cumulative dose of MAVENCLAD is 3.5 mg/kg body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. Each treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight. Following completion of the 2 treatment courses, no further cladribine treatment is required in year 3 and year 4.

Key safety warnings

Cladribine can reduce the body's immune defence and may increase the likelihood of infections. Serious, severe, and opportunistic infections—including events with fatal outcome—have been observed with MAVENCLAD treatment. The incidence of herpes zoster was increased in patients on cladribine. If lymphocyte counts drop below 200 cells/mm³, anti-herpes prophylaxis according to local standard practice should be considered during the time of grade 4 lymphopenia. In clinical studies, 20% to 25% of the patients treated with a cumulative dose of cladribine 3.5 mg/kg over 2 years as monotherapy developed transient grade 3 or 4 lymphopenia. Grade 4 lymphopenia was seen in less than 1% of the patients. The largest proportion of patients with grade 3 or 4 lymphopenia was seen 2 months after the first cladribine dose in each year. Liver injury, including serious cases, has been reported uncommonly in patients treated with MAVENCLAD, especially in patients with a medical history of abnormal liver tests. Patients should have their serum aminotransferase, alkaline phosphatase, and total bilirubin levels assessed prior to initiation of each treatment course. In clinical studies and long-term follow-up of patients treated with a cumulative dose of 3.5 mg/kg oral cladribine, events of malignancies were observed more frequently in cladribine-treated patients (10 events in 3414 patient-years [0.29 events per 100 patient-years]) compared to patients who received placebo (3 events in 2022 patient-years [0.15 events per 100 patient-years]).

Contraindications

MAVENCLAD therapy must not be initiated in patients with hypersensitivity to cladribine or to any of the tablet excipients. MAVENCLAD therapy must not be initiated in patients who are infected with the human immunodeficiency virus (HIV). MAVENCLAD therapy must not be initiated in patients with active chronic infections (tuberculosis, hepatitis). MAVENCLAD therapy must not be initiated in immunocompromised patients, including patients receiving immunosuppressive or myelosuppressive therapy with agents such as cyclosporin, methotrexate, mitoxantrone, azathioprine, natalizumab, or chronic use of corticosteroids. MAVENCLAD is contraindicated in patients with moderate or severe renal impairment (creatinine clearance < 60 mL/min). MAVENCLAD is contraindicated in pregnancy and breastfeeding.

PBS listing

The 10 mg tablet is listed on the PBS with 3 items, restriction type streamlined, at an ex-manufacturer price of A$4486.72.

Regulatory history

MAVENCLAD was first registered on the ARTG on 9 September 2010. The TGA approved MAVENCLAD on 5 December 2017 for the treatment of relapsing-remitting multiple sclerosis (RRMS) to reduce the frequency of clinical relapses and to delay the progression of physical disability. This decision was based on a favourable benefit-risk assessment, supported by new clinical data and a revised dosing regimen that mitigated prior safety concerns. The PBAC recommended MAVENCLAD in July 2018 for relapsing remitting multiple sclerosis, with listing based on acceptable cost-effectiveness if cost-minimised against fingolimod.