Conference Coverage

Lenabasum, a novel cannabinoid, shows promise in dermatomyositis

Publish date: July 28, 2019
By
Kari Oakes

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Cannabinoids in dermatology

Cannabinoids represent a broad class of chemical compounds originally comprised only phytocannabinoids – cannabinoids produced by the cannabis plant. The best-known and most-studied cannabinoids are tetrahydrocannabinol and cannabidiol, which are plant-derived, or “phyto”, cannabinoids. While tetrahydrocannabinol is best known for its mind-altering, munchy-causing properties, it was in fact the study of this illegal substance that led to the groundbreaking discovery of the human endocannabinoid system. (Meaning, we make our very own cannabinoids and receptors for them, which make up an extraordinary biological network that play a role in everything from sensations of pain and itch to mood, inflammation regulation, and wound healing.) Gold star for drugs?

Dr. Adam Friedman

It was this understanding that led to the development of synthetic cannabinoids, like ajulemic acid (aka lenabasum), all of which has created a flurry of investigative productivity and creativity to capitalize on these bioactive agents. That said, development, research and development, and even education in/on this area has been hindered for many years because of both regulatory limitations and negative public perceptions, given the Schedule 1 designation of every component of the cannabis plant (even nonpsychoactive actives) up until a few months ago with the passing of the Farm Bill (which made hemp legal).

However, the interest level among consumers, patients, and physicians is quickly growing regarding the effectiveness of cannabinoids in the treatment of a laundry list of skin conditions and symptoms, including psoriasis, atopic dermatitis, and wound healing. But there are just so many unanswered questions for anyone to be certain about the benefits. We recently published a study surveying 531 dermatologists to get a better idea about our community’s attitude and awareness on cannabinoids as therapeutics, and it turned out there’s a lot we all need to learn (J Drugs Dermatol. 2018 Dec 1;17[12]:1273-8). Some highlights of our findings:

  • Dermatologists are being approached by their patients with questions on this subject matter, and this is more likely to occur in states where medical cannabis is legalized.
  • While more than 90% of respondents agreed that this is an important area for research and development and 86% thought medical cannabinoids should be legal, more than 80% were not comfortable with their understanding or knowledge on this subject matter, which is not surprising given that 64% of respondents incorrectly responded that cannabidiol has psychoactive effects.

With the fast-tracking of lenabasum down the Food and Drug Administration approval pathway for not one but two diseases we as dermatologists manage, I am optimistic that this addition to our much needed armament will serve as further stimulus to expand the role of cannabinoids in the management of dermatologic diseases and spotlight the need for more education and research in this vastly underrecognized yet intriguing and promising space.

Adam Friedman, MD, is professor and interim chair of dermatology, director of translational research, and director of the supportive oncodermatology clinic at George Washington University, Washington, and is on the board of Dermatology News. Dr. Friedman is on the scientific advisory board for Corbus Pharmaceuticals.


 

EXPERT ANALYSIS FROM WCD2019

MILAN – A novel synthetic cannabinoid helped reduce the severity of dermatomyositis and improved patient-reported outcomes in early clinical trials, 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.

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