Novel Nonopioid Dual Action Analgesic Highly Effective Against Post-Surgical Pain in Phase 2b Trial
The new chemical entity from Xgene Pharmaceuticals, XG005, targets both anti-nociceptive and anti-neuropathic pain pathways.
Treatment with the investigational nonopioid multimodal analgesic XG005 provided statistically significant and clinically meaningful reduction of post-surgical pain among adults following bunionectomy, according to a news release from Xgene Pharmaceuticals.1
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Close to half (42%) of participants in the phase 2b clinical trial who received the higher of 2 doses of XG005 had no need to use rescue pain medication and one-third (33%) of those who received the lower dose did not require the additional analgesia.1
Among the group of participants who did require rescue medication, treatment with the new chemical entity increased by 8-fold the time to first use of the add-on treatment and importantly, use of XG005 reduced the amount of opioid medication used by 4 times in the high-dose group. The drug also significantly improved post-surgical sleep in the active treatment vs placebo groups over the first 72 hours and was well tolerated, according to Xgene.1
The oral medication, potentially a first-in-class therapy, has a dual mechanism of action, targeting both antinociceptive and antineuropathic pain pathways, the company said. The combined inhibition of pain signal transmission may provide enhanced pain relief with a positive safety profile.
“There is a substantial need for more efficacious, safer, nonopioid treatment for acute pain, as many patients are unable to get sufficient relief with currently available medicines due to intolerable side effects,” Gene Hsu, PhD, CEO of Xgene, said in the release.1 “We are pleased that the results from this trial showed the excellent therapeutic effect of XG005, with the potential to be a better treatment option compared to current therapies.”1
The multicenter, randomized, double-blind, placebo-controlled phase 2b study evaluated the safety, efficacy and pharmacokinetics of XG005 oral tablets compared to placebo for management of acute pain following unilateral first metatarsal bunionectomy.2 The primary study outcome was summed pain intensity (SPI) from the conclusion of surgery to 48 hours post-surgery, assessed by standard 11-point numeric pain rating scale (NPRS). For secondary outcomes, researchers measured total tramadol (50 mg, PRN) rescue medication consumption, time to first use of rescue medication from end of surgery to 72 hours, Patient Global Assessment (PGA) of pain control at 48 hours and cumulative nausea assessment through 24 hours.2
The study cohort numbered 450 adults aged between 18 to 80 years who were randomly assigned to receive 50 mg XG005, 1250 mg XG005, or placebo. Both active drug and placebo were administered prior to surgery and every 12 hours post-surgery for 72 hours.2
Summary of efficacy outcomes1:
- SPI was statistically lower in both active arms vs placebo over 72 hours (P <.001); maximum pain was mild (< 4.0 NPRS) in the high dose arm vs reaching severe (> 7.0 NPRS) in the placebo arm.
- Median times to first use of rescue medication for high dose, low dose and placebo were 31.47, 12.24 and 4.03 hours, respectively; HR vs placebo 0.18 and 0.24 (P <.001).
- Total opioid consumption over 72 hours was significantly less in active arms than in placebo (P <.001), with Morphine Equivalent Dose of 6.72 (high), 9.38 (low) and 23.86/24.68 (placebo).
- Total acetaminophen use for rescue over 72 hours was significantly less in the active arms than in the placebo (P <.001), with means of 1586 (high), 1976 (low) and 4812.7/4892.74 (placebo) mg.
- PGA on pain control was statistically greater in XG005 arms than in the placebo arm over 72 hours (P <.001).
- Patients’ sleep post-surgery was significantly better in the XG005-treated arms compared with placebo as assessed with Sleep Interference Score (P< .001).
“I have not seen any analgesics showing such great efficacy in well-controlled multiple center trials,” Leon Jiang, MD, PhD, Xgene chief medical officer, said in the company release. “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.”1
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