Simcere’s Sanbexin Emerges as Game-Changer: FDA Grants Breakthrough Therapy Designation to Sanbexin for AIS Treatment

 If your competent? doctor and hospital don't get this installed in their hospital in the next month; YOU NEED TO FIRE THE BOARD OF DIRECTORS FOR INCOMPETENCE!

There are no excuses allowed!

Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? If you don't follow and implement research, you don't belong in stroke.

And look at that, known since February so plenty of time to prepare if they had any competence at all? My God, I'd fire a hell of a lot of people in stroke!

Sublingual Acute Stroke Neuroprotectant Dazzles in Phase III Trial February 2024

And China approved it earlier this month.

China NMPA approves Simcere’s Sanbexin® sublingual tablets for the treatment of Acute Ischemic Stroke December 2024

The latest here:

Simcere’s Sanbexin Emerges as Game-Changer: FDA Grants Breakthrough Therapy Designation to Sanbexin for AIS Treatment

Sanbexin is the first innovative drug for stroke treatment with Breakthrough Therapy designation in the world. Clinical trial results demonstrated that the fast-acting sublingual tablets led to statistically significant improvements in functional outcomes in patients compared with placebo.

The Sanbexin sublingual tablets (edaravone and dexborneol) developed by the Chinese pharmaceutical company Simcere have been granted the Breakthrough Therapy designation by FDA for the treatment of acute ischemic stroke (AIS) recently.

This prestigious designation is backed by significant improvements in efficacy endpoints in the TASTE-SL study, a Phase 3 multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. The results showed improvements in neurological recovery and activities of daily living (ADL) achieved by Sanbexin compared with placebo.

“The FDA Breakthrough Therapy designation not only recognizes the innovation and potential efficacy of Sanbexin, but also highlights the urgent global needs for more effective stroke treatments,” stated Dr. Felix Wang, Senior Vice President of Simcere Pharmaceutical Group Limited. “This designation will expedite the development and review processes, which is essential for a novel drug designed to treat serious, life-threatening conditions.”

In parallel with the FDA Breakthrough Therapy designation in the U.S., Sanbexin sublingual tablets have been approved for market in China by the National Medical Products Administration on December 1, with the first indication aiming at the improvement of neurological symptoms, ADL impairments, and functional impairments caused by AIS.

According to The Lancet, stroke ranks as the second leading cause of death and disability worldwide, with an incidence of 12 million new cases and 6.6 million deaths annually. AIS is the most prevalent type of stroke, accounting for about 70% of all stroke cases, underscoring the importance of timely intervention. As highlighted in “Pragmatic Solutions to Reduce the Global Burden of Stroke”, a report published by The Lancet Neurology in collaboration with the World Stroke Organization, if no urgent measures are taken, the global deaths due to stroke are predicted to rise by 50% by 2050, reaching 9.7 million annually, with economic losses potentially amounting to US$2.3 trillion.

The major goal of intervention in AIS is to salvage the ischemic penumbra—a vital area of brain tissue susceptible to damages. Effective brain cytoprotection has the capability of reducing ischemic brain injury by antagonizing detrimental molecule cascades.

The TASTE-SL study recruited patients from 33 centers aged 18 and 80 who had a National Institute of Health Stroke Scale score of between 6 and 20. They also had a motor deficit score of the upper and lower limbs of 2 or greater, a clinically diagnosed AIS symptom within 48 hours, and a modified Rankin Scale (mRS) score of 1 or less before stroke. Of 956 patients, 42 were excluded.

Among the 914 patients included, the median age was 64 and 66.5% were male. Approximately 49.2% of the patients received Sanbexin sublingual tablets, while the remainder received placebo tablets.

A favorable outcome of an mRS score of 1 or less on day 90 occurred in 64.4% of the patients in the edaravone dexborneol group and 54.7% in the placebo group (odds ratio, 1.50; 95%CI, 1.15-1.95, p = 0.003). Adverse reactions (AR) were comparable between Sanbexin and placebo groups, with metabolic and nutrition disorders being the most common AR.

“The combination of edaravone and dexborneol as active ingredients enables Sanbexin to serve as a multi-target brain cytoprotective agent, significantly reducing cascade damages caused by brain ischemic reperfusion,” Dr. Felix Wang added, emphasizing the drug’s effect on patient recovery.

Professor Dongsheng Fan from Peking University Third Hospital, the principal investigator of this study project, noted, “The TASTE-SL study has provided high-quality evidence-based data for clinical brain cytoprotection, offering robust support for stroke treatment.”

“Breakthrough Therapy designation from FDA is a very big deal. This is the first time it’s happened for a brain cytoprotection agent,” said Dr. Gregory W. Albers, the director of Stanford Stroke Center, Stanford Medical Center. “The sublingual formulation is very easy to give in any stroke setting. A larger number of patients were less disabled because of the medication. With efficacy, a long time window to treatment, and without significant adverse effects, this medication has tremendous potential.”

The designation was granted also due to the sublingual route of administration of the tablets. Unlike other systemic administration drugs which have to travel a longer route to reach liver, reducing the amount and potential potency of the drug being administered, Sanbexin sublingual tablets quickly enters the brain and circulation system once it contacts with saliva beneath the tongue.

As early as 2020, Sanbexin (edaravone and dexborneol concentrated solution for injection) was approved for marketing in China and included in China’s medical insurance directory. Over the past four years, it has treated more than 3 million AIS patients and received wide recognition among clinicians and patients. At current stage, the injection and sublingual formulations are expected to be combined as a sequential therapy, facilitating a complete course of brain cytoprotection for stroke patients to achieve better efficacy.

Yongjun Wang, president of Beijing Tiantan Hospital, emphasized, “The Sanbexin sublingual tablets after marketing will provide patients with further brain cytoprotection and neuroprotection after hospital discharge, making it easier to complete the full course of treatment, thereby simplifying the treatment process for patients and lowering the economic burdens.”

As the first innovative drug globally to receive FDA Breakthrough Therapy designation for stroke treatment, Sanbexin sublingual tablets have already completed Phase 1 clinical trials in healthy volunteers in the U.S. Additionally, Phase 2 clinical trials assessing the sublingual tablets for post-stroke cognitive impairment (PSCI) are currently underway. Looking ahead, Sanbexin sublingual tablets is positioned to not only serve as acute stroke treatments, but also to address subacute and chronic cerebrovascular diseases, thereby benefiting a wider patient population.

“With its rapid absorption and ease of use, Sanbexin sublingual tablets address the crucial needs for effective stroke interventions in emergency settings, benefiting patients worldwide,” concluded Dr. Felix Wang.

China NMPA approves Simcere’s Sanbexin® sublingual tablets for the treatment of Acute Ischemic Stroke

 

You'll have to ask your competent? doctor why the hell edaravone is approved in Japan since 2001 but not the US.

Has your stroke hospital done anything with edaravone in the last decade?

 

• edaravone (12 posts to November 2011)

The latest here:

China NMPA approves Simcere’s Sanbexin® sublingual tablets for the treatment of Acute Ischemic Stroke

NANJING, China, Dec. 4, 2024 /PRNewswire/ -- On November 2, 2024, Simcere Pharmaceutical announced that Sanbexin^® sublingual tablets (generic name: edaravone and dexborneol sublingual tablets), an innovative drug for stroke, has been approved for marketing by the National Medical Products Administration. This product is indicated for the improvement of neurological symptoms, daily activities, and functional impairment due to acute ischemic stroke.

Sanbexin^® sublingual tablets is a dual-target brain cytoprotective agent composed of edaravone and dexborneol. These two active ingredients exert synergistic anti-oxidant and anti-inflammatory effects, which can significantly reduce brain cell damage caused by acute ischemic stroke.

The sublingual tablets are designed for quick disintegration once in contact with saliva under the tongue. This facilitates the active ingredients’ rapid absorption into the blood and brain through the sublingual venous plexus. Compared to conventional oral formulations, sublingual tablets bypass the first-pass hepatic metabolism, which is conducive to higher drug bioavailability and faster onset of action.

Previously, Sanbexin^® injection was approved for marketing in China in 2020. As the world’s only innovative drug approved for stroke since 2015, it has helped over 3 million patients in the past 4 years.

The phase III clinical trial led by Professor Fan Dongsheng of Peking University Third Hospital showed that the patients in the Sanbexin^® sublingual tablets group after 14 consecutive days of drug administration, obtained a significantly higher proportion of functional independence outcome at 90 days post-treatment than those in the placebo group (64.4% vs. 54.7%,). The latest data was published in JAMA Neurology on February 19, 2024.

Professor Fan Dongsheng, Principal Investigator of TASTE-SL and Professor at Peking University Third Hospital mentioned:“Sanbexin^® sublingual tablets has shown significant effects and good safety in improving recovery of cerebral cells and independent living ability during the acute phase in patients with acute ischemic stroke. The more convenient administration allows for sequential therapy with Sanbexin^® injection, facilitating stroke patients to receive a complete course of brain cytoprotection in and outside of the hospital during the acute phase of stroke.”

Professor Wang Yongjun, Director of Beijing Tiantan Hospital, Capital Medical University “The average length of hospital stay for stroke patients in China is about one week, while clinical studies suggest that brain cytoprotective drugs need to be used for 14 consecutive days. Sanbexin^® sublingual tablets is easy to take, allowing patients to receive treatment at home. This can better reduce disability among patients and is also expected to lower medical costs.”

In August 2024, Sanbexin^® sublingual tablets was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for AIS, making it the world’s first innovative drug in the field of stroke treatment to have received such acknowledgment. Currently, a global multi-centered clinical trial of Sanbexin^® sublingual tablets is under preparation.

“The approval of Sanbexin^® sublingual tablets in China is believed to significantly reduce the number of stroke-related disabilities in China.”

Professor Gregory W. Albers, Director of the Stroke Center and the Medical Center at Stanford University commented, ” We are planning to conduct a large-scale Phase III clinical trial of Sanbexin^® sublingual tablets in the United States, hoping to replicate the success of the trial in China and help reduce the global burden of stroke-related disabilities.”

Dr. Marc Fisher, former President of the World Stroke Organization and Professor at Harvard Medical School, commented on this new approval:“Sanbexin^® has gradually gained popularity in China and is now available in a sublingual tablets formulation, with clinical data confirming its safety and efficacy. We are hoping to see trials of Sanbexin^® sublingual tablets conducted outside China. If the trial results are positive and it receives approval in other countries, such as the U.S., it will have a huge impact globally on the treatment of acute ischemic stroke.”

The Sanbexin^® sublingual tablets, with its convenient delivery method, will make stroke prevention and treatment more comprehensive and accessible. Its therapeutic area is expected to be expanded to pre-hospital emergency treatment for the acute phase of stroke, as well as to the treatment for the sub-acute and chronic phases of cerebrovascular diseases, to further promote the recovery of neurological functions and to improve the functional prognosis of stroke patients.

View original content to download multimedia:https://www.prnewswire.com/news-releases/china-nmpa-approves-simceres-sanbexin-sublingual-tablets-for-the-treatment-of-acute-ischemic-stroke-302322300.html

SOURCE Simcere Pharmaceutical Group Limited

Sublingual Acute Stroke Neuroprotectant Dazzles in Phase III Trial

 FYI, make sure you read the caveats.

Sublingual Acute Stroke Neuroprotectant Dazzles in Phase III Trial

Experts raise concerns about analysis and reporting in Chinese study

by Crystal Phend, Contributing Editor, MedPage Today February 20, 2024

For acute ischemic stroke within 48 hours of onset, the novel sublingual combination of edaravone (Radicava) with dexborneol appeared to dramatically improve functional outcomes in the phase III TASTE-SL trial from China.

The chance of a good functional outcome as marked by a modified Rankin Scale (mRS) score of 0-1 on day 90 was 50% improved with the neuroprotectant compared with placebo (64.4% vs 54.7%, OR 1.50, 95% CI 1.15-1.95, P=0.003), reported Dongsheng Fan, MD, of Peking University Third Hospital in Beijing, and colleagues in JAMA Neurologyopens in a new tab or window.

Adverse events (AEs) occurred in most patients in both groups; serious AEs were uncommon and balanced between the two.

"This is a remarkable result, and given that edaravone dexborneol is low cost, simple to administer (even in patients who are unconscious, disabled, or dysphagic), and readily available in China, it has major potential practice implications," said Craig S. Anderson, PhD, and Lili Song, MD, PhD, both of the George Institute for Global Health in Sydney.

In an accompanying editorial, they acknowledged the "litany of failed neuroprotection trials in acute ischemic stroke" over after several decades of considerable investment but noted a "clear rationale" for adjuvant stroke treatment in the endovascular treatment era.

"Many patients have poor access to reperfusion therapy and, even when they do have it, do not have a satisfactory recovery despite achieving a good technical result of recanalization of an occluded vessel. Moreover, in showing the benefits of endovascular therapy within a 6- to 24-hour onset-to-treatment time window in patients with a large ischemic lesion, recent trials have also challenged understanding about how viable vs dead neuronal tissue is defined on brain imaging," they wrote.

Edaravone is a low-molecular-weight drug that appears to protect neurons, glia, and vascular endothelial cells against oxidative stress and inflammation. It is FDA approved for amyotrophic lateral sclerosis. The combination with dexborneol, a component of proprietary Chinese medicine, "is believed to offer a synergistic action," the editorialists noted.

However, they pointed out some serious concerns with the results: "To begin with, the size of the observed treatment effect ... is much higher than would be expected of a neuroprotective agent. Because approximately half of the patients commenced the treatment at 24 hours or longer after symptom onset, this size of benefit is equivalent to that seen with intravenous thrombolysis initiated within the first few hours of an acute ischemic stroke. Therefore, the results challenge our understanding of the 'time is brain' concept of the evolving ischemic penumbra and are contrary to the neutral results of the ESCAPE-NA1 trial, and most recently ESCAPE-NEXT ... which evaluated nerinetide, a highly promising drug that attenuates excitotoxic cell death."

The editorialists suggested chance could be at play in TASTE-SL, which was powered at 80% rather than a more conventional 90% and did not show benefits of edaravone dexborneol in any secondary endpoints, including early neurological impairment in NIH Stroke Scale (NIHSS) scores between baseline and 14 and 30 days.

"It is unfortunate that no ancillary measures of health-related quality of life were collected during follow-up to allow a broader appraisal of the recovery of patients," Anderson and Song lamented.

The researchers, though, chalked the nonsignificant secondary endpoint results up to the substantial number of mild strokes in the trial, with an average NIHSS score of 7.

The trial included 914 patients, ages 18-80 years, who had an NIHSS score of 6-20; a total motor deficit score of the upper and lower limbs of 2 or greater; clinically diagnosed acute ischemic stroke symptoms within 48 hours; and a pre-stroke mRS score of 1 or less.

They were randomly assigned to sublingual edaravone dexborneol (30 and 6 mg, respectively) or placebo comprised of inert dexborneol (60 μg, to simulate the taste of the active drug) twice daily for 14 days.

Limitations included exclusion of a patient who got endovascular thrombectomy and enrollment of only persons of Chinese ethnicity.

The editorialists also pointed to another limitation: "Just before being unblinded to the data toward the end of the study, the steering committee made the decision to use a complex approach to addressing missing primary outcome data in the primary analysis rather than a more conventional complete case analysis of the primary outcome. This included using the last observation carried forward or assigning a worse-case variable (6 for death) in patients with a missing outcome. Given that missingness (loss to follow-up) is invariably not lost at random, this could have influenced the result. Inevitably, this did not occur as they were readily confirmed in secondary imputation, covariate-adjusted, and subsequent complete case analyses."

They also raised the specter of conflicts of interest, as the study authors included employees of three pharmaceutical companies, "including the one that sponsored the study and would naturally have an interest in the trial outcome."

Furthermore, Anderson and Song added to the call for replication of the results in other regions of the world.

"Because maximizing access to reperfusion treatment is at the forefront of modern stroke services, and disease and social reasons for delayed presentation after symptom onset differ across regions, the TASTE-SL results are promising but less relevant to contemporary clinical practice outside of China," they wrote. "However, they provide a clear justification for further evaluations of edaravone dexborneol in other populations, and for individual patient data meta-analysis to be undertaken to determine the totality of the evidence."

"The performance bar is set high, but the benefits offered by safe treatments with only modest effects in reducing the burden of acute ischemic stroke worldwide are considerable," Anderson and Song stated.

• 

  Crystal Phend is a contributing editor at MedPage Today. Follow

Disclosures

The trial was sponsored and funded by grants from Simcere Pharmaceutical and the National Key R&D Program of China.

Fan dislcosed no relationships with industry. Four co-authors are employees of Simcere Pharmaceutical Group. Two co-authors are employees of Neurodawn Pharmaceutical.

Anderson disclosed being principal investigator for the INTERACT3 trial, which was funded by research grants from the Medical Research Council of the U.K., Takeda China, and Hasten Pharma, and receiving fellowship grant support from the National Health and Medical Research Council of Australia.

Song disclosed no relationships with industry.

Primary Source

JAMA Neurology

Source Reference: Fu Y, et al "Sublingual edaravone dexborneol for the treatment of acute ischemic stroke: The TASTE-SL randomized clinical trial" JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2023.5716.

Secondary Source

JAMA Neurology

Source Reference: Anderson CS and Song L "Promising efforts to define a novel approach to neuroprotection for acute ischemic stroke" JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2023.5727.