Positive Results Reported From Pivotal Phase 3 Studies of Crisaborole Ointment in Atopic Dermatitis

FDA review scheduled for January 2017

Positive findings from two pivotal phase 3 studies of investigational crisaborole topical ointment 2% (Pfizer/Anacor Pharmaceuticals) have been published online in the Journal of the American Academy of Dermatology. In both studies, crisaborole achieved statistically significant results on primary and secondary endpoints for the treatment of mild-to-moderate atopic dermatitis (AD) in adults and children (2 years of age and older) compared with vehicle ointment alone.

In both studies, investigators randomly assigned AD patients 2 years of age or older to receive twice-daily applications of crisaborole or vehicle for four weeks. All of the patients had an Investigator’s Static Global Assessment (ISGA) score of mild or moderate disease. The studies’ primary endpoint was an ISGA score at day 29 of clear (0) or almost clear (1), with a two-grade or greater improvement from baseline.

More crisaborole-treated patients than vehicle-treated patients achieved the primary endpoint (32.8% vs. 25.4%, respectively [P = 0.038] in one study, and 31.4% vs. 18.0% [P < 0.001] in the other study). In addition, a greater percentage of patients had clear or almost clear skin in the crisaborole groups compared with the vehicle groups in the two trials (51.7% vs. 40.6% [P = 0.005] and 48.5% vs. 29.7% [P < 0.001]).

Crisaborole topical ointment, 2%, is an investigational nonsteroidal topical anti-inflammatory phosphodiesterase type 4 (PDE4) inhibitor in development for the potential treatment of mild-to-moderate AD. Crisaborole is a boron-containing small molecule that inhibits PDE4 in target cells, which may reduce the production of pro-inflammatory cytokines that are thought to cause the signs and symptoms of AD.

AD is a chronic condition characterized by inflammation and itching. Lesions of AD are commonly red, elevated patches and are often accompanied by pruritus. Approximately 18 million to 25 million people in the United States have AD, and 80% to 90% have mild or moderate disease. AD most commonly appears in childhood, and it has been estimated that between 8% and 18% of all infants and children in the U.S. are affected by the disease.

Current AD treatments reduce inflammation and itchiness to maintain the protective integrity of the skin. Combinations of antibiotics, antihistamines, topical corticosteroids, and topical immunomodulators are the current standard of care. While not approved by the FDA for the treatment of AD, ultraviolet light has also been used to treat the disease.

Pfizer recently completed the acquisition of Anacor Pharmaceuticals, the original developer of crisaborole.

In July 2015, Anacor announced top-line results from the two recently published pivotal studies of crisaborole in patients with mild-to-moderate AD. In October 2015, the company also reported top-line results from a long-term safety study of crisaborole in patients with mild-to-moderate AD. In that study, crisaborole was found to be well tolerated and demonstrated a safety profile consistent with that seen in the phase 3 pivotal studies when used intermittently for up to 12 months.

In March 2016, the FDA accepted for review a new drug application seeking approval of crisaborole for the potential treatment of mild-to-moderate AD in children and adults. The Prescription Drug User Fee Act goal date for the completion of the FDA’s review is January 7, 2017.

Sources: Pfizer; July 13, 2016; Anacor Pharmaceuticals; 2016; and JAAD; July 11, 2016.