Key evidence from clinical trials for alitretinoin

Alitretinoin oral for hand eczema

Toctino® (oral alitretinoin) is marketed by Stiefel Laboratories (UK) and is approved for the treatment of hand eczema in the UK, Europe, Israel and Canada (February 2013).

Safety and effectiveness of oral alitretinoin in patients with severe disease chronic refractory hand eczema current Corticosteroids have been established in two randomized, double-blind, placebo-controlled phase 3 studies.

Study 1

The BACH (benefit of alitretinoin in chronic hand Dermatitis Study) included 1032 patients with severe chronic hand eczema/dermatitis who had no response or a transient response (initial improvement and worsening of disease despite continued treatment) to potent topical corticosteroids or who were intolerant to topical corticosteroids powerful.

All phenotypes of hand eczema included: hyperkeratosis (87%), pompholyx (27%), fingertip dermatitis (43%), and others (15%). Essentially all patients had skin signs. inflammation, consisting of erythema me vesicles.

the primary The endpoint in these studies was the proportion of patients achieving Physician Global Assessment (PGA) scores of clear or nearly clear hands at the end of therapy. The duration of treatment was 12 to 24 weeks.

Alitretinoin treatment led to a significantly higher proportion of patients achieving clear/near clear hands, compared to placebo. The answer was dosedependent. Response rates for different CHE subtypes were also dose-dependent, except for pompholyx patients.

Patients with clear/almost clear hands at the end of treatment were followed up for a further 24 weeks. During that period, no active drug treatment for CHE was allowed. Relapse was defined as the 75% of the initial total injury symptom Punctuation.

In this analysis, the majority of responders who received 10 mg and 30 mg of alitretinoin did not relapse at the end of the follow-up period.

Relapse rates * at the end of follow-up

* Corresponds to a calculation of the last observation carried forward (LOCF)

Study 2

A follow-up study (the second phase 3 study) investigated the efficacy and safety of a second course of treatment in both patients who previously responded to treatment and then relapsed (Cohort A) and in patients who did not respond to therapy (Cohort A). B). Cohort A patients were randomized to the same dose of alitretinoin they received during initial treatment or to placebo in a 2:1 ratio.

The 80% of the relapsing patients in Cohort A, who received repeated treatment with 30 mg alitretinoin, achieved clear/almost clear hands vs. the 8% in the placebo group (p < 0.001).

The 48% of Cohort A relapsers who withdrew on alitretinoin 10 mg achieved clear/almost clear hands vs. 10% in the placebo group (p = 0.1).

Alitretinoin gel 0.1% for Kaposi sarcoma

The US FDA-approved alitretinoin gel (Panretin®; Ligand Pharmaceuticals USA) for the treatment of cutaneous lesions in Kaposi's sarcoma (KS) in 1999. Since then, the drug has been approved in Europe and Canada.

Two multicenter, prospective, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of alitretinoin gel in patients with AIDS-related KS skin lesions.

In both studies, the primary efficacy endpoint was cutaneous KS tumor response rate after 12 weeks of study drug treatment.

KS tumor response rate was assessed by evaluating 3 to 8 KS index lesions according to modified AIDS Clinical Trials Group (ACTG) response criteria applied to topical therapy (i.e., evaluation of reductions in height and area of index lesions only; progressive disease was scored only in treated index lesions and not in non-index lesions and new lesions).

The FDA reviewed photographs of lesions in patients considered responders based on modified ACTG criteria for a cosmetically beneficial response, defined as at least 50% improvement in appearance compared to base, in at least 50% of the index lesions and maintained for at least 3 weeks.

A global evaluation by the doctors was also performed. It considered all of the patient's treated lesions (index and other) compared to baseline. In this evaluation, patients with at least 50% improvement in KS lesions were considered responders.

Study 1

A total of 268 patients were admitted from centers in the US and Canada.

Patients were treated topically three to four times daily with alitretinoin gel or a corresponding vehicle gel for a minimum of 12 weeks.

Responses to alitretinoin gel were observed in both treatment-naïve patients and patients with systemic and/or topical treatment of KS.

Study 2

Study 2 was an international study with a planned enrollment of 270 patients.

The study was stopped early due to positive interim results in the initial data set of 82 patients.

Patients were treated topically twice daily with alitretinoin gel or a corresponding vehicle for 12 weeks.

Responses to alitretinoin gel were observed in both treatment-naïve patients and patients with prior systemic and/or topical treatment with KS.

In both studies, responses occurred in patients with a wide range of baseline CD4+ lymphocyte counts, including patients with CD4+ lymphocyte counts less than 50 cells/mm3. Almost all patients received concomitant Combination antiretroviral therapy.