At high dose, brepocitinib eases symptoms of sarcoidosis affecting skin
Developer says trial results represent 'transformational moment' for treatment
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Receiving a high dose of Priovant Therapeutics’ oral treatment candidate brepocitinib in a clinical trial led to substantial reductions in symptom severity for all participants with cutaneous sarcoidosis, in which the disease affects the skin, new data show.
Further, no serious side effects were reported in the placebo-controlled Phase 2 BEACON study (NCT06978725), which started dosing patients last May, according to the developer.
“This is an incredible milestone for a historically neglected disease – the study … showed a clear difference in patients who received the medication compared [with those given the] placebo, both from the patient and the physician perspective, and [the therapy] appeared to be well tolerated,” Misha Rosenbach, MD, director of the cutaneous sarcoidosis program at the Hospital of the University of Pennsylvania, said in a press release from Priovant announcing the positive trial results.
“This is the sort of data you dream of seeing when you look at trial results – and I would call this a transformational moment for sarcoidosis,” Rosenbach said.
Ben Zimmer, Priovant’s CEO, added: “We are thrilled with the results of the BEACON study and are excited to rapidly move brepocitinib into Phase 3 development for cutaneous sarcoidosis.”
The company plans to meet with the U.S. Food and Drug Administration to go over its plans, with hopes of launching a next-phase clinical trial in cutaneous sarcoidosis this year.
A rare immune system disorder, sarcoidosis is marked by clumps of immune cells called granulomas, which can form in organs throughout the body. Cutaneous sarcoidosis is a form of the disease that affects the skin, usually manifesting as discolored bumps or patches that can appear anywhere on the body.
Oral brepocitinib works by easing inflammation in the body
Brepocitinib is an orally available small molecule designed to lessen the inflammatory activity of immune cells by suppressing TYK2 and JAK1, two proteins with key roles in regulating immune cell activity. The therapy was previously developed by Pfizer, and licensed to Priovant (a subsidiary of Roivant, partly owned by Pfizer) in 2021.
The U.S.-based Phase 2 BEACON trial was designed to test brepocitinib in people with cutaneous sarcoidosis who weighed more than 40 kg (88 pounds) and less than 130 kg (286 pounds).
The study enrolled 31 patients who were randomly assigned to receive brepocitinib at one of two doses — 45 or 15 mg — or a placebo, once a day for 16 weeks, or about four months. Its main goal was to evaluate the therapy’s safety, and results were overall positive: no serious safety issues were reported, according to Priovant.
A key secondary goal was to evaluate the effect of treatment on the Cutaneous Sarcoidosis Activity and Morphology Instrument Activity (CSAMI-A), a standardized measure of disease activity in cutaneous sarcoidosis. CSAMI-A scores range from zero to 165, with higher scores reflecting worse disease.
The results showed that, after 16 weeks, the CSAMI-A score had decreased by a mean of 22.3 points in the high-dose group and 22.2 points in the low-dose group, reflecting less active disease. By comparison, patients given the placebo saw their CSAMI-A scores decrease by a mean of 0.7. That represented a statistically significant difference relative to both treatment groups.
Skin lesions eased for over 60% of sarcoidosis patients on high dose
Significant differences between the high-dose and placebo groups were detected as early as one month and sustained at all time points thereafter, the data showed.
According to Priovant, all 13 participants receiving the high brepocitinib dose experienced a CSAMI-A score drop of 10 points or more, which is considered a clinically meaningful response. Similar improvement was also reported by eight of the 11 people (73%) on the medication’s low dose. One of the seven participants (14%) given the placebo saw the same result.
After 16 weeks of treatment, nearly two-thirds (62%) of people on high-dose brepocitinib had a total CSAMI-A score lower than five points, representing functional remission, or significant reduction in skin lesion activity and improved patient outcomes. This was achieved by 46% of patients on low-dose brepocitinib and none of those on the placebo.
The BEACON study is a watershed moment for the sarcoidosis field, and most importantly, for … patients.
Brepocitinib also led to better outcomes across a range of other measures, including the Investigator’s Global Assessment. Altogether, 69% of participants in the high-dose group achieved the gold standard two-point improvement to “Clear” or “Almost Clear” compared with none on the placebo, the researchers noted.
Moreover, all participants receiving high-dose brepocitinib reported improvements on a patient-assessed measure of overall health, the Patient’s Global Impression of Change. Slightly more than one quarter (29%) of patients on the placebo reported such improvements.
“The BEACON study is a watershed moment for the sarcoidosis field, and most importantly, for our patients,” Rosenbach said.
Zimmer expressed appreciation for all those involved in BEACON, saying, “I would like to thank all of the patients, investigators, and site staff who participated in the study and made this result possible.”
