Home Medizin Neuartiges Medikament ist vielversprechend bei Hidradenitis suppurativa

Neuartiges Medikament ist vielversprechend bei Hidradenitis suppurativa

von NFI Redaktion

In a randomized 16-week Phase 2 study, the oral Bruton tyrosine kinase (BTK) inhibitor Remibrutinib showed promise in patients with moderate to severe Hidradenitis suppurativa (HS).

„Research has shown that the TNF-alpha and IL-17 signaling pathways play an important role in HS,“ said lead researcher Alexa B. Kimball, MD, MPH, from the Clinical Laboratory for Epidemiology and Applied Research in Skin at Beth Israel Deaconess Medical Center, Boston, at the American Academy of Dermatology’s annual meeting. „However, it is believed that several additional pathways contribute to the pathogenesis of the disease.“

The presence of B cells and plasma cells has been reported in HS lesions, even in early lesions, with BTK activation being a central signaling pathway. Kimball and colleagues investigated the safety and efficacy of Remibrutinib (LOU064), an oral, highly selective BTK inhibitor, in 77 adults with moderate to severe HS over at least 12 months in 2 or more anatomical areas with 15 or fewer subcutaneous tunnels.

The study included slightly more women than men, with over 90% of participants being Caucasian. Developed by Novartis, the novel drug is also being investigated for other immune-mediated inflammatory diseases, including chronic spontaneous urticaria and multiple sclerosis.

Of the 77 patients, 33 received 100 mg of Remibrutinib twice daily, 33 received a dose of 25 mg twice daily, and 11 patients received placebo twice daily. The primary endpoint was the proportion of patients achieving a simplified clinical response in Hidradenitis suppurativa (HiSCR) by week 16 compared to pooled placebo. A simplified HiSCR response was defined as at least a 50% reduction in the total number of inflammatory abscesses and nodules without an increase in drainage tunnels compared to baseline.

Kimball, also a Professor of Dermatology at Harvard University, reported that overall, 80.2% of patients completed the treatment: 87.9% and 78.8% in the Remibrutinib 25 mg and 100 mg arms, respectively, and 76% in the pooled placebo arm. The primary reason for treatment discontinuation was patient decision (60.9%). Nearly three-quarters of patients in the 25 mg twice daily Remibrutinib arm (72.7%) achieved the simplified HiSCR endpoint, compared to 48.5% in the 100 mg twice daily Remibrutinib arm and 34.7% in the placebo arm.

In other exploratory results, the HiSCR, HiSCR 75, and HiSCR 90 rates in week 16 were higher in patients in both Remibrutinib treatment arms compared to placebo, and the study drug was also associated with a greater effect on reducing the number of abscesses and drainage tunnels. Specifically, the estimated mean percentage reduction in the number of abscesses was 68% in the 25 mg twice daily arm, compared to 57% in the 100 mg twice daily arm and 49.7% in the placebo arm. Meanwhile, the estimated average reduction in drainage tunnels in the three arms was 55.6%, 43.6%, and 10.2%, respectively.

Researchers also observed a stronger response on the Patient’s Global Assessment of Skin Pain Numeric Rating Scale 30 (NRS30) in patients treated with Remibrutinib compared to those on placebo at week 16 (57.1% in the 100 mg twice daily arm compared to 44.4% in the 25 mg twice daily arm and 30.4% in the placebo arm).

In terms of safety, adverse events (AEs) were mainly of mild or moderate severity, with no deaths reported in any treatment arm and only one serious AE reported: a case of acute pancreatitis in the 25 mg twice daily arm, a testicular abscess in the pooled placebo arm, and a hypertensive crisis in the 100 mg twice daily arm. Treatment discontinuations due to side effects were rare. Infections (mainly upper respiratory infections like nasopharyngitis) were the most common side effects in all treatment arms.

„BTK inhibition could prove to be a promising treatment option for HS,“ concluded Kimball. „This is wonderful news for our HS community. We look forward to determining the optimal dosage for the future.“

Jennifer L. Hsiao, MD, Associate Professor of Dermatology and Director of the HS Clinic at the University of Southern California, Los Angeles, who was asked to comment on the study, said there is „an urgent need for more treatments for patients with HS who suffer from the pain and often life-limiting consequences of this disease.“ She described the study results as „promising.“

„We will see if Phase 3 studies with more balanced demographic characteristics in the Remibrutinib and placebo arms will reproduce these results,“ she continued. „It is exciting to see this potential new drug for HS being further investigated, especially considering the current gap in oral therapy options for the HS patient community. Hsiao was not involved in the study.

Kimball disclosed numerous conflicts of interest with various pharmaceutical companies, including receiving research grants and consulting fees from Novartis. Hsiao disclosed being a board member of the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

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