Rare Daily Staff
Corbus Pharmaceuticals reported that topline results from the phase 3 DETERMINE study of lenabasum in adults with the rare autoimmune disease dermatomyositis failed to show a statistically significant different in total improvement compared with placebo, sending shares down 30 percent on the news.
Dermatomyositis, a form of idiopathic inflammatory myositis, is a chronic, rare and clinically heterogenous condition that can be life-threatening. The autoimmune disease affects approximately 80,000 people in North America, the European Union, and Japan. The signs and symptoms of dermatomyositis reflect multi-organ involvement, which includes distinctive skin rashes usually accompanied by proximal muscle weakness, and can also include pulmonary, cardiac, gastrointestinal, and joint involvement. Patients with dermatomyositis can have recurrent disease flares or chronic progressive disease activity, with increased mortality.
Current treatments include FDA-approved systemic glucocorticoids and off-label use of glucocorticoid-sparing immunosuppressive or immunomodulating agents, but there is significant unmet need for new treatments to achieve disease control because of limited efficacy or toxicity of immunosuppressive agents or refractory disease.
Lenabasum is a novel, oral, small molecule designed to provide an alternative to immunosuppressive treatments for inflammatory or fibrotic diseases. Lenabasum binds to and activates the cannabinoid receptor type 2 (CB2), which is preferentially expressed on activated immune cells, to resolve inflammation and limit fibrosis. Data from animal models and human clinical studies suggest that lenabasum can reduce expression of genes and proteins involved in inflammation and fibrosis. In clinical testing to date, lenabasum has acceptable safety and tolerability profiles.
The study failed to meet its primary endpoint of Total Improvement Score (TIS) at Week 28. Higher TIS values indicate greater overall improvement. At Week 28, the lenabasum 20 mg twice daily group achieved a mean TIS of 28.3 versus the control group mean TIS of 26.7. All subjects, including the control group, received standard background treatments, with 89 percent of dosed subjects receiving one or more immunosuppressive or immunomodulating therapies. Additional pre-specified analyses of the overall effect on TIS of lenabasum 20 mg twice daily versus control group through Week 52 showed a trend of beneficial effect of lenabasum but was still not statistically significant.
This study enrolled subjects with the two major types of dermatomyositis: classic dermatomyositis with both muscle weakness and skin involvement and dermatomyositis with no significant muscle weakness but with skin involvement. Improvement in muscle weakness is heavily weighted in the TIS score. In the overall study, higher TIS scores were seen in those subjects who had muscle weakness and were treated with lenabasum 20 mg twice daily versus the control group. Conversely, the Cutaneous Dermatomyositis Activity and Severity Index (CDASI) activity score, a secondary endpoint in this study, is a validated outcome that was designed to assess inflammatory skin involvement in dermatomyositis. In the overall study, greater improvement (reduction) in CDASI activity scores was seen in subjects with skin involvement but no muscle weakness who were treated lenabasum 20 mg twice daily versus the control group. This is a similar patient population and the same endpoint as was tested in Corbus’ previously completed phase 2 study.
Safety data showed 86.5 percent of lenabasum-treated subjects and 85.9 percent of control subjects had treatment-emergent adverse events (AEs), 11.5 percent of lenabasum-treated subjects and 5.6 percent of control subjects had serious AEs, and no lenabasum-treated subject and one control subject discontinued study drug because of an AE related to study drug.
Data from this study will be presented at an upcoming medical conference.
“We are disappointed that the trial did not meet the primary endpoint of TIS at Week 28,” said Barbara White, chief medical officer and head of research at Corbus. “Nonetheless, we are encouraged by the results when the outcome is matched to the subtype of dermatomyositis in the study. We believe we see clinical activity of lenabasum 20 mg administered twice daily compared to the control group just receiving standard background treatments, with higher TIS scores in classic dermatomyositis subjects with muscle weakness and skin involvement and greater reduction in CDASI activity score in subjects with active skin disease but normal muscle strength.”
“We look forward to discussing the data from the phase 2 and phase 3 dermatomyositis studies with regulatory authorities and seeking their input on next steps,” said Yuval Cohen, CEO of Corbus Pharmaceuticals. “With our strong cash position, we have the resources to both advance our now diversified pipeline while also planning next steps for lenabasum.”
Photo: Yuval Cohen, CEO of Corbus Pharmaceuticals