AMELUZ (5-aminolevulinic acid) - Actinic keratoses

The Committee deems that the clinical benefit of AMELUZ (5-aminolevulinic acid) 78 mg/g gel is moderate in the MA indication.

Considering:

• demonstration in three phase 3 clinical studies of:
  • the superiority of 5-aminolevulinic acid versus placebo for the percentage of patients with complete clearance of lesions 12 weeks after the last red-light photodynamic therapy (PDT) (primary endpoint), with a clinically relevant effect size (86.0% versus 32.9%, p < 0.0001), in adults with mild to severe actinic keratosis (AK) of the extremities, trunk or neck (ALA-AK-CT010 study),
  • the superiority of 5-aminolevulinic acid versus placebo for the percentage of completely cleared lesions 12 weeks after the last red-light PDT (primary endpoint), with a clinically relevant effect size (90.9% versus 21.9%, p < 0.0001), in adults with mild to moderate AK of the face or scalp located in a field cancerization (ALA-AK-CT007 study),
  • the superiority of 5-aminolevulinic acid versus placebo for all the ranked secondary efficacy endpoints in both studies versus placebo, particularly on the percentage of patients with complete clearance of lesions confirmed by histological examination, although the effect size is lower than in the absence of histological confirmation,
  • the non-inferiority of 5-aminolevulinic acid versus METVIXIA (methyl aminolevulinate), for the percentage of completely cleared lesions 12 weeks after natural-light PDT (primary endpoint), in adults with mild to moderate AK of the face or scalp (ALA-AK-CT009 study), with no evidence of a superiority of 5-aminolevulinic acid compared to methyl aminolevulinate,
• a better overall cosmetic outcome with 5-aminolevulinic acid in the studies versus placebo,
• recurrences after 6 or 12 months of follow-up after the last PDT for lesions having had a complete response at week 12 (at 12 months of follow-up: 9.1% and 14.1% with red-light PDT [1 to 2 sessions of PDT] and 19.5% with natural daylight PDT [1 session of PDT] versus 31.2% for methyl aminolevulinate),
• the absence of any comparison with cryotherapy, which remains the reference treatment when lesions are not numerous (≤ 5 lesions),
• the similar safety profile to that of METVIXIA (methyl aminolevulinate), primarily including local reactions, such as irritation, erythema and pain,

the Committee deems that AMELUZ 78 mg/g (5-aminolevulinic acid) gel provides no clinical added value (CAV V) in the treatment of actinic keratosis of mild to moderate severity (Olsen grade 1 to 2) and of field cancerization in adults.