How lenabasum works
Lenabasum is an oral endocannabinoid-mimetic — a compound that mimics the effects of endocannabinoids. Endocannabinoids are naturally-occurring chemicals that play a role in regulating appetite, metabolism, mood, pain, and inflammation.
Lenabasum preferentially binds to cannabinoid receptor type 2 (CB2), which is found primarily on the surfaces of activated immune cells. Upon binding to the CB2 receptors, lenabasum may trigger the production of anti-inflammatory mediators thereby reducing inflammation. Ultimately, lenabasum may act to “turn off” chronic inflammation and halt tissue thickening and scarring (fibrosis) without suppressing the activity of the immune system. Researchers think that reducing inflammation could help prevent permanent tissue damage in the lungs of people with cystic fibrosis.
Lenabasum in clinical trials for CF
Preclinical studies on human lung cells from patients with cystic fibrosis showed that lenabasum stopped the production of two crucial pro-inflammatory cytokines (cell-signaling molecules that trigger inflammation) called tumor necrosis factor alpha and interleukin-6.
Researchers also evaluated lenabasum in a Phase 2 clinical trial (NCT02465450) for the treatment of cystic fibrosis. A total of 85 adults with cystic fibrosis enrolled in the study. The 16-week, double-blind, randomized, and placebo-controlled trial finished in December 2016.
Results showed that lenabasum had acceptable safety and tolerability profiles at all doses tested, which ranged from 1 mg to 40 mg daily. Treatment with 20 mg of lenabasum twice a day was able to reduce the frequency of acute lung exacerbations. This dosage consistently reduced the number of inflammatory cells and inflammatory mediators in the sputum. Forced expiratory volume in one second (FEV1, a measure of lung function) was stable throughout the study for both lenabasum and placebo groups. The most common side effect was a mild dry mouth that occurred in 13% of patients on lenabasum.
A double-blind, placebo-controlled Phase 2 trial, called CF-002 (NCT03451045), enrolled 415 cystic fibrosis patients, ages 12 and older to further investigate the effects of lenabasum. Corbus and the Cystic Fibrosis Foundation co-funded the study. Patients received either 5 or 20 mg of lenabasum or a placebo twice a day for 28 weeks. The main goal of the study was to see whether there is a difference in pulmonary exacerbations between the treatment groups and the placebo group.
Trial results failed to show a statistically significant difference in the rate of exacerbations between the treatment groups and the placebo group. Researchers presented an additional analysis of the data at the 2020 North American Cystic Fibrosis Conference. It showed that patients from five eastern European countries had unexpectedly low numbers of pulmonary exacerbations. When they excluded those patients, researchers found a larger difference in the number of exacerbations between patients receiving treatment and those receiving placebo. The finding suggests that the treatment may provide a possible clinical benefit, although further testing is merited.
Lenabasum has been designated an orphan drug for treating cystic fibrosis in the U.S. and in Europe. The U.S. Food and Drug Administration also granted it fast-track status.
Researchers are testing lenabasum in Phase 2 clinical trials as a potential treatment for other diseases such as scleroderma (NCT02465437 and NCT03398837), dermatomyositis (NCT02466243), and systemic lupus erythematosus (NCT03093402) in which inflammation also is linked to disease progression.
Last updated: Feb. 18, 2021
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