New anti-scarring pill shows encouraging safety in early trial
Oral ifetroban was well tolerated as developer looks toward larger studies
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An experimental oral therapy called ifetroban proved generally safe and was well tolerated in adults with systemic sclerosis (SSc) over one year of treatment, according to top-line findings from a Phase 2a clinical trial.
The trial, called ASSIST-SSc study (NCT02682511), compared once-daily ifetroban against a placebo in 41 adults with SSc, a rare autoimmune disease also called scleroderma. Most reported side effects were mild, and no serious safety issues were tied to the treatment, developer Cumberland Pharmaceuticals announced in a company press release.
However, the study was too small to show whether ifetroban could ease symptoms or slow disease progression. Most patients in both the treatment and placebo groups showed little disease progression over the 12-month period, making it difficult to detect therapeutic differences between the two arms.
Cumberland has reviewed the results with SSc specialists and plans to submit the final clinical study report to the U.S. Food and Drug Administration. The company also plans to analyze blood and tissue samples from the trial alongside heart imaging collected from patients who are continuing treatment in an open-label extension study, in which all participants receive ifetroban. These follow-up analyses will help guide the therapy’s future development.
Unmet needs in SSc and how ifetroban works
In SSc, an abnormal immune response triggers chronic inflammation and the excessive buildup of tough scar tissue, known as fibrosis, across the skin, blood vessels, and vital organs. While existing treatments can slow lung function decline in people with SSc-related lung disease, no approved therapies specifically target or prevent cardiac complications. Because heart and lung problems remain leading causes of death in scleroderma, researchers are focusing on treatments that can prevent internal scarring.
Ifetroban is designed to address this gap as an oral tablet that blocks the thromboxane receptor, a protein that drives blood vessel narrowing, inflammation, and fibrosis. By blocking this receptor, the treatment could help reduce tissue scarring and improve the function of affected organs in people with SSc.
This approach is supported by earlier animal studies of pulmonary arterial hypertension (PAH), a common scleroderma complication where high blood pressure in lung arteries strains the heart and can lead to heart failure. In preclinical models, ifetroban reduced tissue scarring and helped preserve heart function. According to Cumberland, slowing this tissue damage could help preserve vital organ function and improve daily life for patients.
Early safety findings from the ASSIST-SSc trial
Those laboratory findings supported the launch of the Phase 2a ASSIST-SSc trial, which enrolled 31 people with diffuse SSc, a form of the disease associated with widespread skin fibrosis, and 10 with SSc-associated PAH.
Participants were randomly assigned to receive once-daily ifetroban or a placebo for 12 months. Overall, 31 received ifetroban — 22 with diffuse SSc and nine with SSc-PAH — while 10 received a placebo, including nine with diffuse SSc and one with SSc-PAH.
The study primarily focused on evaluating safety and tolerability. Researchers also tracked exploratory measures of heart and lung function, skin thickening, overall disease activity, and patient quality of life.
Overall, the safety profile was consistent with observations from earlier trials of the compound. Digestive upset occurred more frequently in the ifetroban group than in the placebo group, though most instances were considered mild and temporary.
Mild bleeding events were also slightly more common among participants on ifetroban, which aligns with how the drug blocks thromboxane receptors to prevent blood clotting. Importantly, no serious adverse events reported during the yearlong study were considered related to the study drug.
Although the safety findings were encouraging, the trial did not establish whether ifetroban could improve SSc-related complications. Cumberland noted that while the safety data are positive, the small sample size and overall stability of participants across both groups meant the trial could not draw conclusions about ifetroban’s effectiveness, leaving those questions for larger future studies.
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