MAYZENT

First assessment.

Unfavourable opinion for reimbursement in the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.

Role in the care pathway?

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system. Several forms of the disease can be defined, depending on the level of inflammatory activity and the progression of functional disability:

• relapsing-remitting MS (RRMS), characterised by significant inflammatory activity, defined by the occurrence of demyelinating episodes (relapses) localised in the white matter of the CNS, alternating with periods of remission. This is the most common form of MS (80 to 85% of cases).
• secondary progressive multiple sclerosis (SPMS), which is a progressive form of RRMS developing within a median period of 15 to 20 years after the first neurological event and in approximately 50 to 60% of patients with RRMS. These forms are characterised by continuous neurological degeneration, leading to a progression towards irreversible disability, with or without the persistence of inflammatory activity (active and non-active forms).
• and primary progressive multiple sclerosis (PPMS), characterised by continuous and irreversible worsening of disability from the start of the disease, without a remission phase and generally with a lower inflammatory activity.

According to the EMA, the term relapsing MS (RMS) includes patients having presented a single demyelinating event who show dissemination of lesions in time and space on MRI scans, RRMS and SPMS with relapses and excludes PPMS. Among RMS, active forms should be differentiated from highly active forms in accordance with the marketing authorisations of the medicinal products concerned.

The treatment strategy for active SPMS is based on supportive care (rehabilitation therapy, mechanical aids, treatment of spasticity, etc.) to manage the functional disability and on certain medicinal products targeting the residual inflammatory activity of the disease, with no medicinal product having to date demonstrated its efficacy on the medium or long-term progression of disability.

Hence, some β-1b interferons (BETAFERON and EXTAVIA) have an MA for the treatment of active SPMS and other medicinal products are non-specifically indicated in active or highly active RMS (REBIF interferon β-1a, OCREVUS ocrelizumab and MAVENCLAD, cladribine). Medicinal products containing mitoxantrone (ELSEP – NOVANTRONE and generics) also have an MA in the treatment of patients with highly active RMS associated with rapidly evolving disability where no alternative therapeutic options exist.

In addition, other immunomodulatory agents or immunosuppressants are sometimes used off-label for the treatment of active SPMS (rituximab or cyclophosphamide in particular), especially in the first years of the transition to the SP form when the inflammatory activity remains high. Other therapeutic strategies are sometimes developed by the experts. However, there are no robust data confirming the therapeutic benefit of these immunomodulatory agents or immunosuppressants used off-label in these clinical situations.

MAYZENT (siponimod) has no role in the therapeutic strategy for active SPMS in view of the alternatives and available data.