Xgene Pharmaceutical has announced positive results from its Phase 2b trial of XG005, a novel non-opioid analgesic, in patients experiencing acute pain following bunionectomy. The multi-center, randomized, double-blind, placebo-controlled study demonstrated that XG005 significantly reduced post-surgical pain and the need for opioid rescue medication.
The trial, which enrolled 450 patients, evaluated the safety, efficacy, and pharmacokinetics of XG005 oral tablets compared to placebo. Patients were administered either 750 mg or 1250 mg of XG005 twice daily for 72 hours following surgery. The primary endpoint was the summed pain intensity (SPI) over 48 hours post-surgery.
Key Findings from the Phase 2b Trial
Results indicated a statistically significant difference in summed pain intensity over 48 hours between XG005 and placebo groups. Specifically, patients receiving the 1250 mg dose of XG005 experienced significantly greater pain relief. The high-dose group also saw an elimination of rescue pain medication use in 42% of patients, while the low-dose group saw a 33% elimination.
For patients requiring rescue analgesics, XG005 increased the time to first use by eight-fold in the high-dose arm compared to placebo. The median times to first use of rescue medication for the high-dose, low-dose, and placebo groups were 31.47, 12.24, and 4.03 hours, respectively (P< 0.0001).
Furthermore, total opioid consumption over 72 hours was significantly less in the XG005 groups compared to placebo (P< 0.0001). The Morphine Equivalent Dose (MEQ) was 6.72 mg and 9.38 mg for the high and low doses of XG005, respectively, compared to 23.86/24.68 mg for placebo.
Total acetaminophen use, as a rescue medication, was also significantly lower in the XG005 arms (1586.03 mg and 1975.89 mg for high and low doses, respectively) compared to placebo (4812.7/4892.74 mg) (P< 0.0001).
Patient-Reported Outcomes and Safety
Patient Global Assessment (PGA) of pain control was statistically greater in the XG005 arms than in the placebo arm over 72 hours (P< 0.0001). Additionally, patients' sleep post-surgery was significantly improved in the XG005-treated arms, as assessed by the Sleep Interference Score (P< 0.0001).
XG005 was well-tolerated, with no treatment-related serious adverse events reported.
Mechanism of Action and Future Development
XG005 is a novel, non-opioid chemical entity with a dual mode of action, targeting both nociceptive and neuropathic pain signals. It is under development as a potential first-in-class oral treatment for both acute and chronic pain conditions. Xgene is also evaluating XG005 in a Phase 2 trial for cancer-induced bone pain in Taiwan and Mainland China.
"I have not seen any analgesics showing such great efficacy in well-controlled multiple center trials," said Leon Jiang, Chief Medical Officer at Xgene Pharmaceutical. "This compelling efficacy of XG005 overwhelmingly distinguishes it from other analgesics, and we are extremely encouraged to expedite the development for early delivery to patients."
The Need for Non-Opioid Alternatives
"There is a substantial need for more efficacious, safer, non-opioid treatment for acute pain, as many patients are unable to get sufficient relief with currently available medicines due to intolerable side effects," noted Gene Hsu, CEO of Xgene. The acute pain market was valued at approximately USD 50.03 billion in 2023 and is projected to reach around USD 78.36 billion by 2032, highlighting the significant unmet need for improved pain management solutions.
