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MILAN – according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.
Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.
Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.
In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.
Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.
However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.
Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.
Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.
“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.
Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.