ENSPRYNG (satralizumab)

Key points

Favourable opinion for reimbursement as a monotherapy or in combination with immunosuppressive therapy (IST) for the treatment of neuromyelitis optica spectrum disorders (NMOSD) only in adult and adolescent patients from 12 years of age who are anti-aquaporin-4 IgG (AQP4-IgG) seropositive, and who have a relapsing form of the disease not having responded to background immunosuppressive therapy (rituximab, azathioprine, mycophenolate mofetil).

Unfavourable opinion for reimbursement in the other clinical situations of the MA.

What therapeutic improvement?

• Therapeutic improvement in management of the disease in adults, in the same way as SOLIRIS (eculizumab),
• Therapeutic improvement in the treatment of the disease in adolescents aged 12 years and older.

Role in the care pathway?

According to the 2021 French national diagnostic and care protocol (PNDS) relative to NMOSD, the treatment of neuromyelitis optica (NMO) flare-ups is a therapeutic emergency, due to the risk of incapacitating sequelae, in addition to the functional threat and the potential threat to life. In parallel, long-term management (background treatment) is essential in order to reduce the risk of flare-ups, since repeated relapses can cause functional and serious sequelae.

Initial treatment in the event of flare-ups is based on intravenous corticosteroid therapy with high-dose methylprednisolone (1 g/d for adults and 30 mg/kg/day for children from 12 years of age) for 5 to 10 days, followed by long-term oral treatment (1 mg/kg/day) and plasma exchanges in serious flare-ups.

The background treatments used in practice (off-label) and recommended for the prevention of relapses are the following immunosuppressive therapies:

• Rituximab, an anti-CD20, administered IV every 6 months (beneficial effect on the prevention of relapses, significant reduction in annualised rate of relapses),
• Tocilizumab, an anti-IL6 used in NMOSD refractory to conventional immunosuppressive therapies,
• Azathioprine, in combination with an oral corticosteroid therapy for the first six months (reduction in the annualised rate of relapses in adults and children),
• mycophenolate mofetil in combination with an oral corticosteroid therapy for the first six months (reduction in the annualised rate of relapses in adults and children),
• mitoxantrone (reduction in the annualised rate of relapses).

Other medicinal products, such as methotrexate, cyclophosphamide, ciclosporin and tacrolimus, are also used to a more limited degree.

Treatments used in MS (interferons, glatiramer acetate, natalizumab or fingolimod) appear to be ineffective or detrimental.

SOLIRIS (eculizumab), an anti-C5 complement protein antibody, was granted an MA in NMOSD and was evaluated in September 2020 by the Transparency Committee, which restricted its reimbursement to the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody-positive with a relapsing form of the disease, and not responding to background immunosuppressive therapy (rituximab, azathioprine, mycophenolate mofetil).

However, no proprietary medicinal products have an MA in the treatment of NMOSD in adolescent patients. The treatment in adolescents is based on the same off-label immunosuppressive therapies as in adults.

Role of the medicinal product in the care pathway

Considering:

• the superiority of satralizumab as monotherapy and in combination with immunosuppressive therapy demonstrated in two double-blind, placebo-controlled studies, having included patients with a relapsing form of the disease, the majority of whom were anti-aquaporin-4 IgG seropositive and/or had received prior immunosuppressive therapy,
• the absence of direct comparative data versus the immunosuppressive therapies used in practice (off-label), in particular rituximab, or versus eculizumab in adult patients, with the latter having been developed concomitantly,

ENSPRYNG (satralizumab) as a monotherapy or in combination with immunosuppressive therapy is a background therapy for neuromyelitis optica spectrum disorders in adult and adolescent patients from 12 years of age who are anti-aquaporin-4 IgG (AQP4-IgG) seropositive, and who have a relapsing form of the disease not having responded to background immunosuppressive therapy (rituximab, azathioprine, mycophenolate mofetil).

It should be noted that in adults, this medicinal product is an additional treatment option, in the same way as SOLIRIS (eculizumab, with an MA in adults only), in the absence of direct comparative data versus the latter enabling them to be ranked in the therapeutic strategy. The choice between these treatments should be made on the basis of the clinical situation, the safety profile of the medicinal products, their methods of administration and patients’ preferences.

ENSPRYNG (satralizumab) has no role in the other situations of the MA.

Special recommendations

The Committee recommends that treatment with ENSPRYNG (satralizumab) be administered in a multiple sclerosis resource and expertise centre or in a centre specialising in rare inflammatory brain and spinal cord diseases, with prescription restricted to neurologists in the context of a multidisciplinary team meeting justified in view of the risk of using ENSPRYNG (satralizumab) outside the reimbursement scope defined by the Committee on the basis of available efficacy and safety data, particularly first-line use or use in patients who do not have anti-AQP4 antibodies (off-label).