The FDA has granted Breakthrough Therapy Designation to Simcere Pharmaceuticals' edaravone and dexborneol sublingual tablets (Sanbexin) for the treatment of acute ischemic stroke (AIS). This marks Sanbexin as the first innovative drug globally to receive this designation from the agency for stroke. The medication is composed of two active ingredients designed to protect brain cells, offering synergistic anti-oxidant and anti-inflammatory effects. Its sublingual formulation allows for rapid disintegration and absorption into the bloodstream.
Clinical Trial Data
The designation was supported by data from the Phase 3 TASTE-SL study, published in JAMA Neurology, which demonstrated that Sanbexin improved functional outcomes in AIS patients when administered within 48 hours of symptom onset. The trial randomized patients to either edaravone dexborneol (n = 450) or placebo (n = 464), administered twice daily for 14 days, with a 90-day follow-up period. A good functional outcome, defined as a modified Rankin Scale (mRS) score of 0 or 1, was achieved in 64.4% of patients on Sanbexin compared to 54.7% in the placebo group (OR, 1.50; 95% CI, 1.15-1.95; P = .003).
Expert Commentary
"Sanbexin sublingual tablets is effective in improving neurological function recovery and independent living ability of ischemic stroke patients after treatment and apply to a variety of treatment scenarios," said Dongsheng Fan, MD, PhD, director of the neurological department at Peking University Third Hospital and professor of neurology at Peking University. "This phase 3 study of Sanbexin sublingual tablet also provides a high-quality evidence-based basis for clinical brain cell protection, which provides a strong guarantee for stroke treatment."
Trial Design and Patient Population
The TASTE-SL study was a multicenter, randomized, double-blind, placebo-controlled trial involving patients aged 18 to 80 years. Inclusion criteria included a National Institutes of Health Stroke Scale (NIHSS) score between 6 and 20, a total motor deficit score of the upper and lower limbs of 2 or greater, clinically diagnosed AIS symptoms within 48 hours, and a pre-stroke mRS score of 1 or less. The entire patient population consisted of individuals of Chinese Han ethnicity.
Safety Profile
Safety outcomes were similar between the two groups. Adverse events (AEs) occurred in 89.8% of patients on edaravone dexborneol and 90.1% in the placebo group (OR, 0.99; 95% CI, 0.64-1.53). Treatment-related AEs occurred in 13.6% of patients in the edaravone dexborneol group and 10.8% in the placebo group (OR, 1.30; 95% CI, 0.87-1.93). The most common AE was metabolism and nutrition disorders, affecting 46.2% and 48.1% of patients in the respective groups.
Secondary Outcomes and Further Analysis
An ordinal comparison of mRS categories favored the edaravone dexborneol group (common OR, 1.33; 95% CI, 1.05-1.68). However, Sanbexin did not significantly impact other pre-specified secondary outcomes, such as the proportion of patients with an mRS score of 2 or less, changes in NIHSS score from baseline to day 14, or the proportion of NIHSS scores of 1 or less on days 14, 30, and 90. Subgroup analyses, including patients with a history of hypertension, stroke, hyperlipidemia, diabetes, or heart disease, confirmed the primary outcome favoring sublingual edaravone dexborneol over placebo.
Implications and Future Directions
While acknowledging the promising results, experts suggest further evaluations of edaravone dexborneol in other populations and individual patient data meta-analysis to determine the totality of the evidence. The potential benefits of safe treatments with even modest effects in reducing the burden of acute ischemic stroke worldwide are considerable.
