dm+d

Unassigned

New Medicines

Staquis (UK/EU), Eucrisa (US)Mild-to-moderate atopic dermatitis in adults, adolescents and children

Information

Staquis (UK/EU), Eucrisa (US)
New molecular entity
Pfizer
Pfizer

Development and Regulatory status

Licensed but not launched
Approved (Licensed)
Launched
May 21UK launch plans uncertain after Pfizer withdrew its evidence submission to NICE. Consequently NICE has terminated its appraisal and is unable to make a recommendation on crisaborole [14].
Mar 20Approved in EU [13].
Mar 20FDA approved in children aged 3 months to 2 yrs old.[12]
Jan 20Recommended for EU approval by CHMP - the full indication is "for treatment of mild to moderate atopic dermatitis in adults and paediatric patients from 2 years of age with ≤ 40% body surface area (BSA) affected”. The medicine should be prescribed by physicians experienced in the treatment of atopic dermatitis [11].
Dec 19Crisaborole still pre-registration in EU; list of outstanding issues discussed at December meeting of the EU CHMP [10].
Jun 18Filed in EU using centralised procedure [9].
Apr 17Anacor has launched crisaborole 2% ointment in the US for treatment of patients with mild to moderate atopic dermatitis, aged two years and older [8].
Dec 16Pfizer buys out Anacor [7].
Dec 16Approved in the US [6].
Jan 16New Drug Application submitted to FDA for crisaborole topical ointment 2%, for the treatment of mild-to-moderate atopic dermatitis in children and adults [5].

Category

Crisaborole, a non-steroidal boron-containing small molecule, inhibits PDE-4, which then inhibits the release of TNF-α, IL-12 and IL-23 and other inflammatory cytokines [2].
Atopic eczema is common and the prevalence is increasing. Eczema affects 20% of school children in developed countries and 2-18% of adults [3].
Mild-to-moderate atopic dermatitis in adults, adolescents and children
Topical

Further information

Yes

Trial or other data

Sep 21Draft NICE guidance does not recommend crisaborole. Evidence from clinical trials shows it improves severity of atopic dermatitis compared with unmedicated ointment. However, this is based on assessing atopic dermatitis in a way that is not used in UK clinical practice, does not capture outcomes that are important to patients, and is a subjective and unreliable way of assessing atopic dermatitis severity. Also, there are no trials directly comparing crisaborole with topical calcineurin inhibitors indirect comparisons are inconsistent and difficult to interpret [14].
Jul 17Pfizer has initiated a phase IIa randomised, double-blind, vehicle-controlled trial to characterise the mechanism of action and efficacy of crisaborole 2% ointment for the treatment of patients with mild to moderate atopic dermatitis (C3291001; NCT03233529). The trial is enrolling approximately 40 patients in Canada [8].
Jul 15AD-301 = NCT02118766 and AD-302 = NCT02118792 [2].
Jul 15Data from 2 PIII trials (n=1522) showed a statistically significant improvement for mild-to-moderate atopic dermatitis patients on crisaborole vs. placebo, in the percentage of patients achieving success in IGSA (achieving a score of 0 or 1). In Study AD-301 32.8% of patients receiving crisaborole vs. 24.4% of patients receiving placebo (p=0.038) achieved the primary outcome of ISGA 0/1 at day 29. The primary outcome was met by 31.4% vs. 18% or patients in Study AD-302 [4].
Jul 15In a randomised, double-blind, vehicle-controlled phase IIa trial, 46 pts with mild-to-moderate atopic dermatitis received crisaborole (2% ointment twice daily for 6 weeks, n=25) or placebo (vehicle, n=21). Crisaborole showed greater improvement over vehicle in Atopic Dermatitis Severity Index (ADSI) score after 28 days. In the final analysis, 68% vs. 20% of lesions treated with crisaborole and vehicle showed improvement in ADSI score respectively (p < 0.05). The proportion of lesions achieving total or partial clearance (ADSI score ≤2.0) at day 28 was 52% vs. 16% with crisaborole and vehicle respectively. The ADSI scores are the sum of severity scores of five clinical features (erythema, pruritus, exudation, excoriation and lichenification) from 0 (none) to 3 (severe) for each feature, for a total score of 0 to 15 [2]. Similar positive results were seen in a phase II, dose-ranging trial involving 86 adolescents with mild-to-moderate atopic dermatitis, who were randomised to receive OD or BD application of crisaborole for 28 days. At day 29, pts showed greater improvements from baseline in ADSI scores (primary endpoint) in the 2% crisaborole BD gp (71%) vs. the 0.5% BD gp (62%). The percentage of lesions that achieved total or partial clearance was also higher at the 2% BD dosage (62%), compared with 0.5% BD (50%). According to results from the ´maximal use systemic exposure´ (MUSE) trial of crisaborole (2% applied BD) in 34 paediatric and adolescents with atopic dermatitis, treatment with the 2% ointment resulted in an Investigator Static Global Assessment (ISGA) score of 0 ("clear") or 1 ("almost clear") in 65% of pts, following four weeks treatment. Mean pruritus scores improved by 62%, and an average of 78% reduction in affected body surface area was observed [1,2]. Anacor Pharmaceuticals initiated two PIII trials in March 2014 in the US and enrolled ~ 750 pts (NCT02118766 and NCT02118792). Positive preliminary results were announced in July 15, showing statistically significant results for all primary and secondary endpoints and a good safety profile. Full data from these trials are expected in the Q2 of 2015. Anacor is also conducting an open-label long-term safety study to evaluate the drug’s intermittent use for up to 12 months. Participants of either phase III trial will be eligible to roll over into the extension trial until approximately 500 pts are enrolled [1].

Evidence based evaluations