A daily pill brought back facial skin color for about one in five adults with vitiligo

PALE PATCHES of skin on the face and hands are often the first sign of vitiligo, a lifelong disease in which a person's own immune cells destroy melanocytes, the cells that give skin its color. About 0.4% of people worldwide have been diagnosed with it. On November 2nd Nature Medicine published the full results of two trials of povorcitinib, a once-daily pill made by Incyte, an American drug company. The lead author is Khaled Ezzedine of Henri Mondor University Hospital and Paris-Est Créteil University, in France, and the senior author is Amit G. Pandya of the Palo Alto Foundation Medical Group, in Sunnyvale, California. After a year on the pill, 18.9% of patients in each trial regained at least three-quarters of the lost color on their face.

Inside the cells of the skin, enzymes called JAKs pass along the chemical signals that call killer immune cells to the melanocytes. Povorcitinib blocks one of them, JAK1, which makes it a JAK inhibitor. Incyte already sells ruxolitinib, a cream that blocks JAK1 and JAK2, and the pill is meant for patients whose doctors judge that they need a whole-body treatment. Incyte gave the headline numbers in its quarterly results on April 28th. The new paper sets out the full design, the statistics and the side effects, after review by outside scientists.

Incyte ran two trials, called STOP-V1 and STOP-V2, with the same design in 916 adults at hospitals in Europe, North America and Japan. Running the same experiment twice, known as replication, makes it less likely that a single lucky result carries the case. In each trial a computer assigned patients by chance either to the drug or to an identical dummy pill, the placebo arm, and neither the patients nor their doctors knew which they were taking. This design, called randomized and double-blind, keeps hopes and expectations from tilting the result. The comparison group matters because some patients regain color without any drug.

Before the trials began, the researchers fixed one measure to judge success, the primary endpoint. A dermatologist scored how much of the face was pale and how pale it was, under an ultraviolet lamp in a darkened room. A patient counted as a success if that score improved by at least 75% after 52 weeks, a target the paper calls F-VASI75. In STOP-V1 it was met by 18.9% of the 233 patients on the drug and 6.8% of the 234 on placebo. In STOP-V2 the figures were 18.9% of 223 patients on the drug and 3.1% of 226 on placebo. The public trial registry records list the same measure, so it was not changed after the results came in.

The absolute difference is the plain gap between the two groups, which was about 12 percentage points in STOP-V1 and about 16 in STOP-V2. The paper also gives odds ratios, a way of saying how many times higher the odds of success were on the drug, of 3.1 and 7.5. The odds ratio in STOP-V2 is larger because fewer placebo patients improved in that trial, since the drug group reached 18.9% in both.

The authors list several limits. About four in five patients on the drug did not reach the main target. Across the whole body, a 75% improvement was reached by only 2.6% of 233 patients on the drug against 1.3% of 234 on placebo in STOP-V1, and 2.3% of 223 against none of 226 in STOP-V2. The trials compared the pill only with placebo and not with any other treatment. Between 80% and 85% of the patients were white, which leaves less evidence for darker skin, and the comparison lasted just one year. Incyte funded the trials and the writing of the paper, and four of its co-authors are Incyte employees.

The side effects need watching over a longer period. Acne affected 10.7% and 10.8% of patients on the drug in the two trials, against 3.0% and 2.2% on placebo. Four patients on the drug developed basal cell carcinoma, a common and slow-growing skin cancer, and no one on placebo did. One patient on the drug had a blood clot in the lungs, a pulmonary embolism, together with a clot in a leg vein. Facial color was still returning at week 52, and every patient can now take the drug for a second year in an extension that is still under way. Its results will show whether the color keeps returning and whether the side effects stay uncommon.