ZEPOSIA (ozanimod)

Key points

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

What therapeutic improvement?

No clinical added value in the therapeutic strategy for RRMS on the basis of currently available data.

Role in the care pathway?

Relapsing remitting multiple sclerosis (RRMS) is 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.

As soon as the RRMS 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 first-line therapeutic options may be proposed: beta interferons (AVONEX, REBIF, BETAFERON, EXTAVIA, PLEGRIDY), glatiramer acetate (COPAXONE), teriflunomide (AUBAGIO), dimethylfumarate (TECFIDERA). In the event of active RMS, ocrelizumab (OCREVUS) may be used. The choice of treatment should be made on the basis of the safety profile of the medicinal products, their method of administration and patients’ preferences.

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

• Fingolimod (GILENYA) and natalizumab (TYSABRI) have an MA restricted to highly active forms of RRMS,
• Alemtuzumab (LEMTRADA) has been restricted by the Committee to highly active forms of RRMS despite first or second-line treatment,
• Ocrelizumab (OCREVUS) may also be used in highly active RMS (recurrent remittent (RR) or secondary progressive (SP)), if it has not been used as first-line therapy. However, no robust data has assessed its efficacy and safety as an alternative to second-line treatments or in the event of failure of these products,
• Finally, mitoxantrone (ELSEP – NOVANTRONE and generics) is a salvage treatment that has an MA in highly active forms of RMS (RR or SP) associated with rapidly progressing disability where no therapeutic alternatives exist.

It should be noted that ozanimod and fingolimod have not been the subject of a direct comparison, despite having the same pharmacological profile.

In rare cases, where RRMS is severe and rapidly progressing from the outset, treatment with natalizumab or fingolimod may be recommended as first-line therapy in accordance with the MA of these medicinal products. However, the use of alemtuzumab or mitoxantrone should not be considered as first-line therapy in the absence of sufficient data given the frequency of serious adverse events associated with these medicinal products. In addition, the Committee highlights the fact that no robust data is available confirming the therapeutic benefit and safety of use of an induction strategy compared to an escalation strategy.

Stabilisation of the disease under either of these treatments is assessed by the number and severity of residual relapses, as well as the development of new lesions on MRI. There is no robust data assessing the benefit of long-term continuation of these powerful immunosuppressive therapies in stabilised patients. Their safety and efficacy in terms of the prevention of disability in the long term have yet to be established.

Role of the medicinal product in the care pathway

ZEPOSIA (ozanimod) is a first-line treatment option in active forms of recurrent remittent multiple sclerosis.

Its superiority has been demonstrated versus interferon, INF β-1a (AVONEX, 30 µg IM, once weekly) in terms of annualised relapse rate. However, there is no data available demonstrating an effect on the reduction of disability progression.

Its short-term safety profile (median follow-up of 50 months and maximum of 71 months) appears to be acceptable, but there are uncertainties concerning its long-term safety given the known profile of other medicinal products belonging to the S1P receptor modulator family.

There is no comparative data versus the other medicinal products available in the treatment of RRMS, meaning that the drug cannot be positioned compared to these.

Hence, the choice between the various treatments in RRMS should be made on the basis of the safety profile of the medicinal products, their method of administration and patients’ preferences. It is also necessary to consider whether patients are planning a pregnancy.