Novel Ointment Effective in Actinic Keratosis

WASHINGTON — For patients with actinic keratosis, an apoptosis-promoting topical ointment may be a viable treatment option, according to phase III trial data presented here.

In two identically designed placebo-controlled studies, about half of patients receiving the agent, called KX2-391, achieved 100% clearance of actinic keratosis at day 57, compared with 5%-13% of patients receiving placebo, reported Edward Lain, MD, of Austin Institute for Clinical Research in Texas, at the American Academy of Dermatology meeting.

KX2-391 is an inhibitor of Src kinase activity and tubulin polymerization; both actions should have the effect of upregulating apoptosis in proliferating cells, Lain explained. Actinic keratosis lesions occasionally progress to skin cancer and are one of the most common reasons that people visit dermatologists.

In one of the trials, 44% of patients receiving the ointment versus 5% of those treated with inert vehicle achieved 100% actinic keratosis clearance. In the other, the corresponding rates were 54% and 13%, respectively. Responses were somewhat less common among male patients compared with women, though still significantly more common than in the placebo groups.

Serious adverse events were rare (no more than 2%) in both studies and didn’t differ between treatments. However, 11.4% and 24.7% of KX2-391 recipients developed local skin reactions in the two studies. Only a handful of placebo patients showed such reactions.

In total, the two studies enrolled about 700 patients. Participants had a treatment area that usually consisted of four to eight visible actinic keratosis lesions on the scalp or face with an area of 25 cm². The investigations were performed at a total of 62 U.S. medical sites. The ointment was applied daily by the patient over the course of 5 consecutive days and left in place for about 12 hours. Lain said compliance rates were 99%.

“The KX2-391 ointment is actually quite interesting for dermatology. It’s been used, this mechanism of action at least, in the oncology space for well over 10 years both for CML [chronic myeloid leukemia] and for solid tumors. It’s an oral drug when used in oncology,” said Lain.

Among the safety population — those who applied the KX2-391 at least one time — the safety results showed that KX2-391 was very well-tolerated, Lain said. There were no related clinically significant abnormal EKGs, laboratory findings, physical exams, or vital signs.

Developer Almirall had announced topline results with the product last July. The company has an agreement with Athenex to commercialize KX2-391 in the U.S. and Europe. Further clinical studies to support FDA approval, if any, are Athenex’s responsibility to conduct.