Lenabasum shows promise for diffuse cutaneous systemic sclerosis
The selective cannabinoid receptor type 2 agonist lenabasum exhibited an acceptable safety profile while improving outcomes in patients with diffuse cutaneous systemic sclerosis, according to results of a phase II study.
“In the open-label extension of the phase II JBT101-SSc-001* trial, lenabasum continues to have acceptable safety and tolerability in diffuse cutaneous systemic sclerosis with no severe or serious adverse events [AEs],” said the researchers led by Dr Robert Spiera, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, Weill Cornell Medical College, New York City, New York, US.
“We look forward to continuing our investigations to assess the role of lenabasum as a new treatment option for patients with diffuse cutaneous systemic sclerosis,” said Spiera, who presented the findings at EULAR 2018.
Thirty-six patients who completed the double-blind, placebo-controlled JBT101-SSc-001 trial were enrolled in the open-label extension trial and received lenabasum at a dose of 20 mg twice a day for one year. Ninety-four percent (n=34) were receiving immunosuppressive drugs at baseline. Patients received treatment for a mean 45 weeks and 19 patients completed 60 weeks of treatment, with a mean 9.5-week drug interval between the end of the double-blind and start of the open-label phases.
One hundred and seventy-one AEs occurred during the course of the open-label phase affecting 92 percent (n=33) of patients. Of these, eight patients had mild AEs, 21 had moderate AEs, and three had severe AEs, with one patient experiencing a life-threatening AE. Seven patients had AEs that were thought to be lenabasum-related, though none were severe AEs. [EULAR 2018, abstract OP0006]
The most frequently occurring AEs (≥10 percent of patients) were upper respiratory tract infections (22 percent), urinary tract infections (14 percent), diarrhoea (11 percent), and skin ulcers (11 percent), while 8 percent of patients experienced mild intermittent dizziness.
One patient developed renal crisis (seven days after initiating prednisone 60 mg/day prescribed by a doctor not involved in the study) which resulted in two severe and one life-threatening AE that were considered unrelated to lenabasum.
Treatment discontinuation occurred in three patients, two due to AEs and one due to withdrawal of consent.
Aside from a tolerable safety profile, lenabasum also appeared to improve clinical outcomes in patients. Among the 25 patients who completed 52 weeks of treatment in the open-label phase, ACR CRISS** scores improved by 56 percent from the start of the double-blind phase, while modified Rodnan Skin Score reduced by 8.6, HAQ-DI*** reduced by 0.14, Physician Global Assessment reduced by 0.9, and 5-D Itch Questionnaire reduced by 2.3. Forced vital capacity percentage predicted was stable from the beginning of the double-blind study with a mean 0.4 percent change.
“Our results are very encouraging and reinforce the positive findings from the double-blinded placebo-controlled part of the study with regard to safety and tolerability,” said Spiera.
“There is a critical unmet need for safe and effective therapeutics for patients with diffuse cutaneous systemic sclerosis,” said Professor Thomas Dörner, Chairperson of the EULAR 2018 Abstract Selection Committee.
“These results demonstrate a significant step forward in the clinical development of a potentially impactful treatment for people suffering with this devastating disease,” he said.