MAVENCLAD

• Key points

Favourable opinion for reimbursement in the treatment of adult patients with highly active relapsing multiple sclerosis (MS) as defined by clinical or imaging (MRI) features.

Clinical benefit now low (previously it was insufficient) in this indication.

• What therapeutic improvement?

No clinical added value in the management of highly active R-MS.

• Role in the care pathway?

As soon as the RR-MS diagnosis has been established, rapid initiation of long-term treatment is recommended to reduce relapse frequency and the progression of the disability in the short term. Several treatment options can be offered as first-line treatment: beta interferons (AVONEX, REBIF, BETAFERON, EXTAVIA, PLEGRIDY), glatiramer acetate (COPAXONE), teriflunomide (AUBAGIO), dimethylfumarate (TECFIDERA) or ocrelizumab (OCREVUS) in case of active R-MS. The choice of treatment should be made based on the safety profile of the medicinal products, the method of administration and patients’ preferences.

When the  inflammatory activity of the disease, assessed clinically (number and severity of relapses) and by MRI criteria (T1 Gd+ lesions, T2 lesion load, etc.), becomes or remains high, despite first-line long-term treatment, the initiation of a more active treatment is recommended. The following medicinal products may be used as second and later-line treatment, according to the conditions defined by their MA and following consultation of a resource and expertise center:

• Fingolimod (GILENYA) and natalizumab (TYSABRI) have an MA restricted to highly active forms of RR-MS; these are the reference treatments at this stage of the disease,
• Alemtuzumab (LEMTRADA) has been restricted by the Committee to highly active forms of RR-MS despite first or second-line treatment,
• Ocrelizumab (OCREVUS) may also be used in highly active R-MS, if it has not been used as first-line therapy. However, no robust data have assessed its efficacy and safety as an alternative to second-line treatments or in case of failure of these products,
• Finally, mitoxantrone (ELSEP – NOVANTRONE and generics) is a rescue therapy that has an MA in highly active forms of R-MS associated with rapidly progressing disability where no therapeutic alternatives exist.

In rare cases, where RR-MS is severe at the outset and rapidly progressing, treatment with natalizumab or fingolimod may be recommended as first-line therapy in accordance with the MA of these medicinal products.

Role of the medicinal product in the care pathway:

MAVENCLAD (cladribine) is a therapeutic option in patients with highly active R-MS. Its efficacy has only been established versus placebo, in patients with predominantly not very active RR-MS, in terms of annualised relapse rate and imaging criteria. The data in highly active RR-MS are based on post-hoc analyses and no data in highly active forms of SP-MS, included in the MA, are available.

In the absence of comparative data with current treatments for highly active R-MS (natalizumab, fingolimod, alemtuzumab and ocrelizumab) and due to still limited knowledge related to its safety of use, the Committee recommends reserving the use of MAVENCLAD (cladribine) for patients failing to respond to or ineligible for these therapeutic alternatives.