Intravenous loberamisal, a novel dual-target neuroprotectant, improved functional outcome in patients with ischemic stroke, results of a phase 3 study showed.
In addition, an exploratory element of the study showed the highly selective small-molecule agent also reduced poststroke depression and anxiety.
“Loberamisal was associated with a 13% absolute increase in the proportion of patients achieving excellent functional outcomes(NOT 100% RECOVERY! So, still a failure! Damn it all, 100% recovery is the only goal and you're COMPLETELY FAILING!) at 90 days, with a favorable safety profile,” study investigator Shuya Li, MD, director of the Clinical Trial Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, toldMedscape Medical News.
She said the findings bolster confidence in the novel agent’s efficacy and justify further neuroprotectant studies in patients with stoke.
The findings were presented on February 6, 2026, at International Stroke Conference (ISC) 2026.
First-In-Class Agent
Reperfusion therapy is a key therapeutic approach for acute ischemic stroke. However, not all patients with stroke are eligible for the therapy due to the strict eligibility criteria including a narrow therapeutic time window.
In addition, about 30% of patients who do receive reperfusion therapy fail to achieve an excellent functional outcome.(Only 10% fully recover! get your statistics right! That's a horrendous failure rate!)
To improve outcomes, the investigators are developing neuroprotective therapies that could help address a significant unmet medical need in China, where approximately 3.94 million new stroke cases occur each year and ischemic stroke accounts for 72% of cases.
Stroke researchers have been investigating postsynaptic density protein 95 (PSD-95) inhibitors that disrupt the NMDAR/PSD-95/nNOS complex. These agents have shown promise in mitigating ischemic brain injury and exerting neuroprotective effects, particularly when administered within 3 hours of symptom onset.
While other groups are exploring PSD-95 inhibition in stroke, Li’s group is focusing on loberamisal, a first-in-class agent that not only inhibits PSD-95 but also enhances alpha2-gamma-aminobutyric acidA receptor activity.
Preclinical studies showed that loberamisal reduced neuronal excitotoxicity and neuroinflammation while also exerting antidepressant and anxiolytic effects.
Early Promise
A recent phase 2 study published in Stroke and Vascular Neurology showed that compared with placebo, loberamisal administered once daily for 10 days at doses of 20 mg, 40 mg, or 60 mg had a comparable safety profile and demonstrated signals of efficacy. The 40 mg dose was associated with the most favorable outcomes.
The current study enrolled 997 adults with ischemic stroke across 32 centers. The median age was approximately 63 years, the median National Institutes of Health Stroke Scale (NIHSS) score was 8, and the median time from symptom onset to treatment initiation was 25 hours. Participants were ineligible for endovascular thrombectomy (EVT).
Participants were assigned within 48 hours of suspected stroke onset to receive either placebo or 40 mg of intravenous loberamisal. The drug was administered as a 1-hour intravenous infusion once daily for 10 consecutive days.
Investigators and participants were blinded to treatment assignment. The primary efficacy outcome was an excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1 at 90 days.
Study results showed that 69.7% of patients in the loberamisal group achieved the primary outcome compared with 56.3% of those in the placebo group (risk ratio [RR], 1.24; 95% CI, 1.12-1.36; risk difference, 13.28).
Secondary analyses supported the primary findings. A sliding dichotomy analysis of the mRS at 90 days showed results consistent with the primary outcome (adjusted RR, 1.23; 95% CI, 1.07-1.42).
Reduced Depression and Anxiety
The overall distribution of mRS scores at 90 days favored loberamisal. However, there were no significant between-group differences in NIHSS score changes at 10 or 30 days or in 90-day Barthel Index scores.
An exploratory outcome assessed poststroke depression and anxiety using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Depression affects an estimated 30% of patients with stroke and anxiety approximately 25%, and both are strongly associated with poorer functional recovery after stroke.
Results showed significant reductions in the risk for severe depression (RR, 0.65; 95% CI, 0.45-0.94 for MADRS ≥ 22 at 90 days) and anxiety (RR, 0.68; 95% CI, 0.47-0.99 for HAM-A ≥ 21 at 90 days) in the loberamisal group compared with placebo.
Overall safety profiles were comparable between groups, with lower rates of serious adverse events (8.6% vs 10.7%) and all-cause mortality (1.2% vs 2.0%) in the treatment group.
Li said her team is considering a larger follow-up study in broader patient populations, potentially including those who have undergone EVT.
In the current trial, a relatively small proportion of patients received intravenous thrombolysis (approximately 17%), and patients undergoing EVT were excluded. In addition, the study population was limited to patients in China.
A ‘Big Win’
Commenting for Medscape Medical News, ISC Chair Lauren Sansing, MD, professor of neurology at Yale School of Medicine in New Haven, Connecticut, described the excellent functional outcomes as encouraging and noted that the findings represent “one of the first big wins in the neuroprotection space.”
Sansing emphasized that a 48-hour treatment window could make loberamisal accessible to a much broader patient population, noting that a large proportion of patients with stroke globally present within the first 2 days.
She noted that although the trial was large, it was conducted exclusively at centers in China and emphasized that additional data from more geographically diverse populations will be important before broader clinical adoption.
ISC Vice Chair Bijoy Menon, MD, a neurologist in Calgary, Alberta, Canada, also commented on the findings. He noted that the trial was not designed to enroll patients in the hyperacute phase of stroke, but rather those who were not candidates for thrombectomy or thrombolysis.
Menon, who has been involved in research on the PSD-95 inhibitor nerinetide, said the results are significant, describing the study as the first large trial to demonstrate a positive signal in the neuroprotection and neurorecovery space.
This study was funded by NeuroDawn Pharmaceutical Co., Ltd. Li, Menon, and Sansing reported having no relevant disclosures.
