FDA Grants Breakthrough Therapy Designation to Sanbexin for Acute Ischemic Stroke

The FDA granted breakthrough therapy designation to edaravone and dexborneol sublingual tablets (Sanbexin; Simcere Pharmaceuticals) as potential treatment for acute ischemic stroke. The sublingual tablets are an innovative first drug to be designed for treatment of stroke and granted this designation.¹

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The active ingredients in the tablets—edaravone and dexborneol—have antioxidant and anti-inflammatory effects which can be used to reduce brain cell injury or impairment. Due to the formulation, it disintegrates upon contact with saliva when placed under the tongue, allowing rapid absorption into the blood.¹

The designation is based on significant improvements in efficacy metrics in a clinical trial study. The multicenter, randomized, double-blind, parallel, placebo-controlled phase 3 trial demonstrated that the proposed drug significantly improved neurological recovery and independent living ability compared with the placebo.¹

Investigators included individuals aged 18 to 80 years who had a National Institutes of Stroke Scale (NIHSS) score between 6 and 20, and the sum of the fifth upper limb score and lower limb score was 2 or greater after onset of disease. Onset time was within 48 hours, according to the clinical trial information. Individuals were excluded if they had intracranial hemorrhaging, severe disturbance of consciousness, transient ischemic attack, severe mental disorders and dementia, or severe active liver diseases.²

Investigators were given either the sublingual tablet or a sham comparator, with the primary outcome including Modified Rakin Scale (mRS) score of 1 or less after 90 days of treatment initiation. Patients’ mRS score, good functional outcome, changes in NIHSS score, NIHSS score of 1 or less on day 14, and NIHSS score of 1 or less on day 90.²

Investigators included 914 individuals with a median age of 64 years and were 66.5% male. Approximately 49.2% received sublingual edaravone dexborneol and 50.8% receiving the placebo. Investigators found that the primary analysis population had missing data on mRS was considered as 6 for those who did not have 1 post-baseline measurement of mRS (8 in both groups) or discontinued treatment or follow up due to adverse events (8 in the treatment group and 14 in the placebo group). Further, the score for patients with at least 1 valid post-baseline measurement was 24 and 10, respectively.³

A favorable outcome of mRS score of 1 or less on day 90 occurred in 64.4% or patients in the study drug group and 54.7% in the placebo group, according to the study authors. For secondary outcomes, the distribution of patients across mRS categories demonstrated good function outcomes for those in the study drug group; however, there were no other effects on the prespecified secondary outcomes.³

In terms of safety, 89.8% of those in the edaravone dexborneol group and 90.1% in the placebo group experienced adverse events (AEs), with treatment-related AEs occurring in 13.6% and 10.8%, respectively.³

REFERENCES

1. Breakthrough Therapy designation for Sanbexin sublingual tablets granted by the United States Food and Drug Administration. News release. Simcere Pharmaceuticals. September 5, 2024. Accessed September 5, 2024. https://prnmedia.prnewswire.com/news-releases/breakthrough-therapy-designation-for-sanbexin-sublingual-tablets-granted-by-the-united-states-food-and-drug-administration-302239018.html

2. Phase III Clinical Trial of Y-2 Sublingual Tablets in the Treatment of Acute Ischemic Stroke. ClinicalTrial.gov identification: NCT04950920. Updated August 22, 2023. Accessed September 5, 2024. https://clinicaltrials.gov/study/NCT04950920

3. Fu Y, Wang A, Tang R, et al. Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial. JAMA Neurol. 2024;81(4):319–326. doi:10.1001/jamaneurol.2023.5716