Istesso Limited has announced results from its Phase 2b clinical trial of leramistat in rheumatoid arthritis (RA), revealing promising outcomes in bone protection despite not meeting its primary endpoint. The 12-week randomized, double-blind, placebo-controlled study evaluated the drug's efficacy in adults with moderate-to-severe RA who showed inadequate response to methotrexate treatment.
While the trial did not achieve the primary endpoint of ACR20 improvement versus placebo, leramistat demonstrated significant benefits in key secondary endpoints, particularly in preventing bone erosion progression - a critical factor in RA-related disability and mortality.
Clinical Impact and Disease Burden
Rheumatoid arthritis affects approximately 17.6 million people globally, with projections suggesting this number will nearly double to 31.7 million by 2050. Bone erosions, appearing early in the disease course, affect up to 60% of patients within their first year of diagnosis, leading to substantial joint damage and functional impairment.
The study's findings on bone protection are particularly significant given that bone erosions are a central feature of RA, appearing early and contributing significantly to long-term disability. Current treatment options have shown limited success in addressing this aspect of the disease.
Key Study Findings
The trial demonstrated several notable outcomes:
- Statistically significant reduction in bone erosion progression
- Meaningful improvements in disability measures
- Significant reduction in fatigue symptoms
- Favorable safety profile with adverse event rates comparable to placebo
Novel Mechanism and Safety Profile
Leramistat represents a first-in-class, once-daily oral medication with a unique mechanism of action that augments the body's natural repair response. The drug's safety profile proved encouraging, with adverse events primarily mild in nature and resolving without intervention. No significant changes in clinical chemistry, blood parameters, vital signs, or cardiovascular health were observed.
Fatigue Management
One of the study's notable findings was leramistat's impact on RA-related fatigue, a symptom affecting up to 70% of patients. Fatigue in RA patients often leads to job loss and significantly impacts quality of life, with current treatments showing minimal effectiveness in addressing this symptom.
Future Directions
Istesso plans to conduct additional Phase 2 studies to further evaluate leramistat's potential in promoting adaptive tissue repair, both in RA and other chronic conditions. The company is considering positioning the drug as a combination therapy with existing disease-modifying anti-rheumatic drugs (DMARDs).
The drug has already received FDA Fast Track and Orphan Drug Designation for idiopathic pulmonary fibrosis (IPF), highlighting its potential broader therapeutic applications beyond RA.
