CHICAGO — Crisugabalin, a novel selective gamma-aminobutyric acid (GABA) analogue, was highly significantly effective in patients with moderate-to-severe central neuropathic pain.

Results of a phase 3 trial of more than 400 patients showed that those randomly assigned to receive crisugabalin at 20-40 mg had a significant reduction in daily pain scores at week 12 compared with those who received a matching placebo, meeting the primary endpoint. Notably, treatment response was observed as early as week 1 of the trial.

This effectiveness for the active treatment was also found in subgroups who had pain following a spinal cord injury (SCI) or stroke. 

This treatment effect was also observed in subgroups of patients with pain following SCI or stroke.

In addition, secondary outcomes demonstrated improved sleep, mood, and quality of life, both in the overall study population and within these subgroups.

The most common adverse events were dizziness, somnolence, and peripheral edema, with most considered mild to moderate in severity, occurring in the early stage of medication, and resolving spontaneously.

“These results support crisugabalin as an effective and safe therapeutic option for central neuropathic pain patients,” said study investigator Xiaochong Fan, MD, Department of Pain Management at the First Affiliated Hospital of Zhengzhou University in Zhengzhou, China.

The study was presented on April 21 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

Approved in China

Crisugabalin is a novel, highly selective GABA analogue that functions as a third-generation ligand of the calcium channel alpha-2-delta-1 subunit. It was approved in 2024 in China for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia in adults, based on results from prior phase 3 trials. China is currently the only country where it has received regulatory approval. 

Its mechanism of binding to subunits in order to reduce calcium influx and decrease the release of excitatory neurotransmitters is similar to pregabalin (Lyrica), a medication that was first approved by the FDA in 2004 and is now used for several indications, including neuropathic pain. Crisugabalin, however, has a 23-fold higher subunit binding affinity vs pregabalin.

The multicenter trial included more than 400 patients in China with moderate-to-severe central neuropathic pain who were randomly assigned to receive 20-40 mg doses of crisugabalin (n = 208; mean age, 54 years; 70% men) or a matching placebo (n = 205; mean age, 53 years; 64% men) twice a day for 12 weeks. 

Subgroup analysis was also conducted in those with SCI pain (105 receiving crisugabalin and 103 receiving placebo) and poststroke central neuropathic pain (103 and 102, respectively).

The primary outcome was the change from baseline to week 12 in the Average Daily Pain Score (ADPS).

Secondary outcome measures included the visual analog scale (VAS), average Daily Sleep Interference Scale (ADSIS), short-form McGill Pain Questionnaire (SF-MPQ), Patient Global Impression of Change, the 5-level EQ-5D, the Chinese Profile of Mood State (POMS-C), and the Hospital Anxiety and Depression Scale (HADS).

New Standard of Care?

Results showed a significant reduction in change from baseline on the ADPS for the active treatment compared with placebo in the full study population (-2.4 vs -1.15, respectively; P < .0001) and in the subgroups with SCI (-2.5 vs -1.2; P < .0001) and stroke (-2.3 vs -1.1; P < .0001).

ADPS response rates for ≥ 30% and ≥ 50% reductions in pain were also significantly higher with crisugabalin compared with placebo in both the overall population and across subgroups (all comparisons except for one, P < .01; for active treatment vs placebo for ≥ 50% reduction, P < .05). 

In addition, the active treatment group scored significantly higher on the VAS, ADSIS, and Patient Global Impression of Change (all, P < .0001), as well as the EQ-5D (P = .0001), HADS (P = .002), and POMS-C (P = .008).

For adverse events, dizziness (6 cases in the total crisugabalin group vs 4 in the total placebo group), somnolence (6 vs 5 cases, respectively), and peripheral edema (12 vs 0 cases) were the most common. 

Fan noted that the study showed clinically meaningful pain relief, “including in the challenging poststroke pain population where previous pivotal trials have failed.”

“With its rapid onset, robust efficacy, and favorable safety profile, crisugabalin may represent a potential new standard of care for these underserved patients,” he added. 

New Option, Familiar Mechanism

The trial design reflects a standard approach commonly used in neuropathic pain research. Jessica Robinson-Papp, MD, professor and vice chair for clinical research at the Icahn School of Medicine at Mount Sinai in New York City, noted that such studies typically enroll large, well-defined patient populations and use a 12-week placebo-controlled design to meet regulatory expectations.

Robinson-Papp, who was not involved in the research, added that the drug has been on her radar because of its similarity to other GABA-related therapies in terms of mechanism and target.

She said there is ongoing interest in new treatments for neuropathic pain, particularly those that may offer improved efficacy or fewer side effects than existing options.

“Even if it’s an incremental change and not a new mechanism of action, anything we can get that is better tolerated for our patients and provides more options is always welcomed,” she said.

The study was funded by Haisco Pharmaceutical Group Co., Ltd. Fan and Robinson-Papp reported having no relevant financial relationships.