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RAXONE 150 mg (idébénone)

Opinions on drugs - Posted on Mar 03 2022

Reason for request

Reevaluation

Key points

Favourable opinion for reimbursement in the treatment of visual impairment in adolescent and adult patients with Leber's hereditary optic neuropathy (LHON).

The clinical benefit now moderate (previously it was insufficient) in this indication.

What therapeutic improvement?

Therapeutic improvement in the management of the disease.

Role in the care pathway?

According to the 2017 international consensus of European and North American experts, the management of LHON includes genetic counselling, informing the patient about potentially preventable lifestyle risk factors (smoking, drinking, toxic environmental factors) and for subacute and dynamic cases, the use of idebenone at the currently approved dose of 900 mg per day. According to the international consensus statement, treatment with idebenone should be discontinued in non-responder patients and is currently not recommended in patients in the chronic stages of the disease.

The Transparency Committee had given  an unfavourable opinion for the reimbursement of RAXONE (idebenone), in the management of LHON, following its initial assessment of this proprietary medicinal product due to negative results in the phase 2 RHODOS study versus placebo. However, it was made available in the context of a cohort compassionate use programme (ATU), which ended in June 2021.

In practice, medicinal products (glutathione, vitamin E or co-enzyme Q1010) are used due to a mechanism of action (antioxidant medicinal products) suggesting that they may be of benefit in this disease. However, their efficacy has not been demonstrated and they are not recommended.

Recently, LUMEVOQ (lenadogene nolparvovec), a gene therapy medicinal product, was made available via a named-patient compassionate use programme (ATU) in 2019, followed by a cohort compassionate use programme (ATU) in July 2021. Its use is limited to patients with loss of vision due to LHON caused by a confirmed G11778A ND4 mitochondrial mutation, the main mutation observed in NOHL.

In addition to lifestyle and dietary measures, management includes rehabilitation therapy for vision loss.

Role of the medicinal product in the care pathway

RAXONE (idebenone) is a first-line therapy in the treatment of visual impairment in adolescent and adult patients with Leber's hereditary optic neuropathy (LHON).


Clinical Benefit
Moderate

The Committee deems that the clinical benefit of RAXONE 150 mg (idebenone) film-coated tablets is moderate in the MA indication.

Clinical Added Value
minor

Considering:

  • demonstration of a superiority of idebenone versus no therapy, in the phase 4 comparative LEROS study versus a historical cohort, in terms of clinically relevant benefit (defined by clinically relevant recovery or clinically relevant stabilisation of visual acuity) in adults and adolescents with LHON with symptoms for less than one year (primary endpoint: 42.3% of eyes versus 20.7%, p = 0.0020);
  • the unmet medical need in a rare, disabling disease that progresses to blindness,

But in view of:

  • the non-optimal nature of this demonstration due to the methodology (non-randomised, open-label, versus a historic cohort);
  • the absence of available data concerning the visual field, which is also impacted in this disease;
  • a safety profile primarily marked by rhinopharyngitis (frequency ≥ 1/10) and gastrointestinal disturbances (diarrhoea: frequency ≥ 1/10) but including a hepatic risk (elevated liver enzymes and hepatitis: important potential risk indicated in the RMP and of unknown frequency according to the SPC);

the Committee considers that RAXONE 150 mg (idebenone) film-coated tablets provide a minor clinical added value (CAV IV) in the treatment of visual impairment in adolescent and adult patients with Leber's hereditary optic neuropathy (LHON).

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