medwireNews: Primary analysis of the phase 3 RESOLVE-1 trial fails to show efficacy with lenabasum in patients with diffuse cutaneous systemic sclerosis (dcSSc).
This was despite favorable findings in a previously reported phase 2 study of the oral cannabinoid receptor type 2 agonist.
Among 375 patients with dcSSc randomly assigned to receive lenabasum, at either 5 or 20 mg twice a day, or placebo, American College of Rheumatology (ACR) Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) scores at 52 weeks were “high and comparable” in all three groups, with median scores of about 0.8 points, and no significant differences.
Secondary outcomes, including changes in modified Rodnan skin score, HAQ-DI, and forced vital capacity (FVC) percent predicted were also similar across the three groups.
Presenting the findings at the EULAR 2021 Virtual Congress, Robert Spiera (Hospital for Special Surgery and Weill Cornell Medical College, New York, USA) commented that the “efficacy outcomes in the placebo group far exceeded what was expected,” which made it difficult to discern treatment effect on top of placebo.
Robert Spiera discusses the phase 3 RESOLVE-1 findings (7:11)
He explained that the patients participating in the trial were allowed to be taking background immunosuppressive therapy, as long as it was stable for at least 8 weeks prior to entry, so as to “reflect real-world clinical practice.” This involved the majority of patients in each group, at between 78% and 89%, with around half of patients in each group taking mycophenolate, and around a third of patients taking two or more immunosuppressive therapies.
Indeed, Spiera said that background immunotherapy, and mycophenolate specifically, “significantly affected the results.” In a prespecified analysis, taking mycophenolate at baseline was found to be significantly associated with ACR CRISS score, leading the researchers to conduct post-hoc observations of mycophenolate that showed patients taking it had a greater improvement in ACR CRISS score than those not taking immunosuppressive therapy (0.94 vs 0.35 points).
But this mycophenolate benefit declined with duration of use, with patients who had been taking it for more than 2 years showing less improvement in ACR CRISS score than patients who had been taking it for a shorter duration.
This was also the case for FVC percent predicted, and post-hoc analysis showed that patients taking background mycophenolate for more than 2 years were more likely to have stable (within 5%) FVC percent predicted over 1 year if they took lenabasum than if they took placebo, at 64% versus 35%. But he cautioned that these findings will need to be confirmed in further studies.
Lenabasum was also shown to be well tolerated with fewer serious and severe adverse events compared with placebo and with no potentially or definitely treatment-related adverse events leading to discontinuation of the drug.
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