This is a 6-month double blind randomized 2:1 placebo-controlled study with two arms (placebo, biotin 300 mg/day). The study will be followed by a 6-month extension phase during which all patients will receive biotin 300 mg/day.

Inclusion Criteria:

• Age: 25 to 80 years, inclusive
• Male or female subjects with probable or confirmed ALS (revised international El Escorial criteria, Forbes et al., 2001).
• Patients presenting first motor deficits due to ALS for a maximum of three years at the first consultation in an ALS centre.
• Patients monitored for at least 6 months in an ALS centre or for whom the previous monitoring parameters are available (excepted for MIP and SNIP).
• Patients who have lost at least 5 points on the ALSFRS-R (ALS functional rating scale) during the last 12 months or at least 2 points during the preceding 6 months
• Patients who have been treated with riluzole for at least 3 months at a stable dose. In case of intolerance to this product or refusal for this treatment, patients who have not been treated with riluzole for at least 1 month before inclusion
• For patients with spinal form (onset of the disease affecting limbs) or respiratory form, slow vital capacity > 60% of predicted value.
• For patients with a bulbar form, slow vital capacity > 60% of theoretical value or, if spirometry not assessable (severe bulbar disability), patient should not have significant abnormality in both nocturnal capnography and nocturnal oximetry (median pCO2 (carbon dioxide partial pressure ) < 52 mmHg, SaO2 (arterial oxygen saturation ) < 90% less than 5% of the time during night) less than 3 months prior inclusion.
• Patients who are willing to give written consent (or oral consent in the presence of a trusted person if the patient is no longer able to write)
• Patients likely to be able to participate in all scheduled evaluation and complete all required study procedures (except for spirometry in bulbar patients with severe disability).

Exclusion Criteria:

• Patients on non-invasive ventilation for respiratory insufficiency due to ALS for more than 10 hours a day
• Patients with an ALSFRS-R score at inclusion of < 20 (maximum score without disability = 48)
• Patients who have lost less than 5 points on the ALSFRS-R during the last year or less than 2 points during the preceding 6 months
• Patients with a gastrostomy
• Patients who have lost more than 15% of their reference weight (defined as weight before disease onset)
• Patient with dyspnoea at rest or with the least effort (score < 3 on the dyspnoea item of the ALSFRS-R)
• Patients with dementia
• Patient with severe or rapidly progressive form of ALS for whom the investigator estimates the life expectancy less than 3 months
• Patients with another progressive disease that has not been stabilized at the time of inclusion
• Patients with cancer, except basal cell carcinoma, for less than 5 years, or who require continuous treatment for cancer even if it is older
• Pregnant women.
• Subject who are not covered by a social security scheme.
• Subject under temporary or permanent Judicial Protection.
• Contraception: Both male subjects, and female subjects who are not either surgically sterile (tubal ligation/obstruction or removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least one year confirmed by a negative hormone panel), must commit to using two highly effective method of birth control for the duration of the study and for two months after the treatment termination.