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Key clinical point: Anabasum had a favorable safety profile and was well tolerated in patients with either refractory skin-predominant dermatomyositis or diffuse cutaneous systemic sclerosis.
Major finding: Treatment with anabasum resulted in greater improvement in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) score at 12 weeks, compared with placebo (–9.3 vs. –3.7 points, respectively; P = .02) and also in the ACR Combined Response Index in Systemic Sclerosis (CRISS) at 16 weeks, compared with placebo (P = .044).
Study details: Two 12-week, phase 2 studies of anabasum in patients with dermatomyositis or systemic sclerosis.
Disclosures: The studies were funded by Corbus, and the dermatomyositis study was additionally supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Spiera reported receiving research support from Corbus and many other pharmaceutical companies. He is a consultant to Roche-Genentech, GlaxoSmithKline, Boehringer Ingelheim, and CSL Behring. Some of the investigators in both studies were employees of Corbus.
SAN DIEGO – Results from two phase 2 studies of the investigational agent anabasum provide evidence supporting its safety and efficacy in patients with refractory skin-predominant dermatomyositis or diffuse cutaneous systemic sclerosis.
Anabasum (JBT-101) is a nonimmunosuppressive, synthetic, oral cannabinoid receptor type 2 agonist being developed by Norwood, Mass.–based. It works by triggering resolution of innate immune responses, said Barbara White, MD, a rheumatologist who is chief medical officer for Corbus. “It restores homeostasis, gets rid of inflammation, turns off active fibrotic processes, and helps clear bacteria if it is present – all without immunosuppression,” she explained in an interview at the annual meeting of the American College of Rheumatology. “A drug that would restore homeostasis in the setting of an ongoing immune response has the potential to be helpful in multiple autoimmune diseases.”
The mean age of the study participants was 53 years and most were white. Even though 19 of the patients were on immunosuppressants at baseline, both cohorts had mean CDASI scores in the 33-35 range, which can be considered severe.
The investigators, led by, of the University of Pennsylvania, Philadelphia, reported that anabasum-treated subjects experienced a medically meaningful improvement in mean CDASI scores, with a reduction of at least 5 points at all visits after week 4 and reaching –9.3 at the end of the study, compared with –3.7 points in the placebo group (P = .02). They also found that 56% of subjects in the anabasum group had a 10-point reduction or more in CDASI score, compared with only 18% in the placebo group (P = .09). In addition, no subjects in the anabasum group developed skin erosions during the active dosing period, compared with 36% of subjects in the placebo group (P = .05).
The researchers also observed that, compared with subjects in the placebo group, those in the anabasum group had greater improvement in patient-reported global skin disease and overall disease assessments, skin symptoms (including photosensitivity and itch), fatigue, sleep, interference with activities, pain, and physical function. No serious, severe, or unexpected adverse events occurred in the anabasum group. Adverse events included dizziness, dyspepsia, headache, and increased appetite.
There is not a Food and Drug Administration or European Medicines Agency–approved drug for refractory skin-predominant dermatomyositis, “so this is encouraging,” Dr. White said.
Dr. Spiera reported that patients in the anabasum group had greater improvement in ACR CRISS, compared with placebo-treated subjects over 16 weeks (P = .044). They also had greater improvement and less worsening in individual CRISS core measures, including modified Rodnan Skin Score, Patient Global Assessment, Physician Global Assessment, and the Health Assessment Questionnaire Disability Index. Patient-reported outcomes of systemic sclerosis skin symptoms, itch, and the Patient-Reported Outcomes Measurement Information System–29 (PROMIS-29) domains of physical function, pain interference, and sleep also improved for the anabasum group, compared with the placebo group (P less than .05 for all).
An analysis of paired skin biopsies before and after treatment with the assessor blinded to treatment assignment demonstrated that patients treated with anabasum were more likely to show improvement in fibrosis and inflammation and less likely to show worsening than were those treated with placebo, consistent with what was observed clinically. In apresented at the meeting, gene expression analysis from specimens before and after treatment also revealed that anabasum treatment (as opposed to treatment with placebo) was associated with changes relevant to pathways involved in fibrosis and inflammation.
“This is the first double-blind, randomized, placebo controlled trial in diffuse cutaneous systemic sclerosis to demonstrate a clinical benefit using the CRISS as an endpoint, with a drug that was safe and well tolerated in the trial,” Dr. Spiera said. “These results bring hope to patients and their physicians that anabasum may be an effective drug for systemic sclerosis where currently there are no proven treatments.”
Both studies were sponsored by Corbus, and the dermatomyositis study was also sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some of the investigators in both studies were employees of Corbus. Dr. Spiera reported receiving research support from Corbus and many other pharmaceutical companies. He also is a consultant to Roche-Genentech, GlaxoSmithKline, Boehringer Ingelheim, and CSL Behring. He is a member of the Rheumatology News editorial advisory board.
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