Cebranopadol hemicitrate

▎药明康德内容团队编辑 Tris Pharma今日宣布，在研疗法cebranopadol，在治疗拇囊炎切除术后中度至重度急性疼痛的关键性3期临床试验ALLEVIATE-2中达到主要临床终点，与安慰剂相比显著减轻患者疼痛。此前，cebranopadol在治疗腹壁整形手术后中度至重度急性疼痛的3期临床试验ALLEVIATE-1中也达到试验主要终点。基于这些积极结果，该公司计划今年向美国FDA递交新药申请（NDA）。 试验数据显示，ALLEVIATE-2临床研究达到了主要终点，即在给药后2小时至48小时内，使用疼痛数字评分量表（NRS）计算曲线下面积（AUC2-48）为指标，显示疼痛强度有统计学上显著的降低。具体而言，每日口服cebranopadol（400 µg）治疗组与安慰剂组相比，疼痛强度的最小二乘均值差为56.1（p<0.001）。研究中另一患者队列接受口服即释型阿片类镇痛药oxycodone治疗。活性对照组与安慰剂相比显示出更好的镇痛效果，但其平均镇痛效果低于cebranopadol。 ▲Cebranopadol在临床试验ALLEVIATE-2中与安慰剂相比显著降低患者疼痛（图片来源：参考资料[1]） 患者在镇痛不足时可使用额外镇痛选择，即补救治疗。试验结果显示，在为期7天的研究期间，接受cebranopadol治疗的患者中无需使用阿片类补救药物的比例显著高于接受安慰剂的患者（57.5%比28.4%；p<0.001）。此外，cebranopadol总体耐受性和安全性良好，未观察到严重不良事件，最常见的不良事件为恶心。 该公司表示，ALLEVIATE-1和ALLEVIATE-2临床研究结果，加上几项人体滥用潜力（HAP）研究中显示的强劲安全性数据，将提交给美国FDA，作为潜在批准的依据。Tris公司计划在即将召开的医学会议上报告ALLEVIATE-1和ALLEVIATE-2临床试验的完整结果。 Cebranopadol是一种潜在“first-in-class”的疼痛治疗药物，作用机制为伤害感受肽/孤啡肽FQ（NOP）受体和µ-阿片肽（MOP）受体双重激动剂。与阿片类药物相比，它有望在提供显著镇痛效果的同时，降低严重副作用、依赖性和成瘾风险。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Tris Pharma Announces Positive Results from ALLEVIATE-2 Phase 3 Pivotal Trial for Cebranopadol, an Investigational First-in-Class Oral Dual-NMR Agonist, for the Treatment of Moderate-to-Severe Acute Pain. Retrieved March 6, 2025, from https://www.businesswire.com/news/home/20250306271136/en 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

MONMOUTH JUNCTION, N.J.--(BUSINESS WIRE)--Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company, today announced positive topline results from its ALLEVIATE-2 Phase 3 pivotal clinical trial evaluating cebranopadol, an investigational therapy, for the treatment of moderate-to-severe acute pain in patients following bunionectomy surgery. The company also detailed additional positive data from the ALLEVIATE-1 Phase 3 pivotal clinical trial in patients following abdominoplasty surgery from which topline data were recently announced. These results add to the growing body of data underscoring the promising efficacy and safety profile of cebranopadol, a first-in-class pain therapy involving dual-nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonism. This dual-NMR agonist has the potential to deliver significant pain relief comparable to opioids with minimized risk of significant side effects, dependence and addiction by leveraging the body’s pain biology modulation processes, synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor. “We are in desperate need of effective medications that provide opioid-level analgesia while minimizing the risk of misuse and abuse,” said Jeff Gudin, M.D., anesthesiologist at the University of Miami, Miller School of Medicine. “Both the ALLEVIATE-1 and -2 trials, as well as promising results from the previous human abuse potential studies, demonstrate cebranopadol’s potential to fill this unmet need for patients suffering from moderate-to-severe acute pain. The strong analgesic effect, exceeding that observed with oxycodone in the bunionectomy study, coupled with low abuse potential, demonstrates the power of agonizing the NOP/MOP receptor system, which represents a breakthrough in our understanding of pain biology.” “With our Phase 3 program for cebranopadol in the treatment of moderate-to-severe acute pain complete, we now have a comprehensive data package that will be submitted to the FDA as the basis for potential approval,” said Ketan Mehta, CEO and founder of Tris. “If approved, cebranopadol has the potential to redefine the standard of care for acute pain management, offering a first-in-kind treatment option for patients in need.” ALLEVIATE-2 Phase 3 Results: Significant Pain Reduction in Cebranopadol-Treated Patients Following Bunionectomy Surgery The results of the ALLEVIATE-2 clinical study achieved its primary endpoint of demonstrating a statistically significant reduction in pain intensity as measured using the Pain Numeric Rating Scale (NRS) Area Under the Curve for two to 48 hours (AUC2-48) following dosing. Specifically, treatment with oral cebranopadol 400 µg once per day resulted in a statistically significant reduction in pain intensity compared to placebo (LS Mean difference [SE] of 56.1 [13.49]; p<0.001; see Table 1, Figure 1). In a separate arm of the study, oxycodone immediate release (IR) 10 mg was administered orally, four times per day. While as expected, oxycodone demonstrated more pain relief compared to placebo, its mean activity was lower than the mean activity observed by cebranopadol as measured via NRS score. Additionally, cebranopadol was generally well tolerated and exhibited a favorable safety profile, with no serious adverse events observed. The most common adverse event was nausea. ALLEVIATE-2 Pain Following Bunionectomy Surgery Cebranopadol 400 µg QD Oxycodone IR 10 mg QID Placebo Comparison to placebo LS Mean Difference (SE) AUC2-48 223.4 (9.58) 250.4 (9.53) 279.5 (9.51) from placebo -56.1 (13.49) -29.1 (13.50) - 95% confidence interval (-82.5, -29.7) (-55.5, -2.6) - p-value < 0.001 0.031 - Post hoc comparison to oxycodone LS Mean Difference (SE) AUC2-48 -27.0 (13.96) 95% confidence interval (-54.3, 0.4) - - p-value 0.054 - - Table 1 Patients were allowed the use of additional analgesic options, or “rescue medication,” if analgesia was not sufficient; first line rescue was ibuprofen, and second line was oxycodone IR 5 mg. The use of rescue medication was a secondary endpoint in the ALLEVIATE-2 trial. The results demonstrated that over the course of the seven-day study period, the proportion of patients receiving cebranopadol who did not require opioid rescue was significantly higher than patients receiving placebo (57.5% versus 28.4%; p<0.001). In addition, total doses of rescue medication were lower for cebranopadol compared to placebo (LS mean difference [SE] of 7.8 [2.68]; p=0.004). “These are extremely encouraging results that emphasize the important role dual-NMR drugs could play in treating moderate-to-severe acute pain with much lower risk of the misuse, physical dependence, addiction or overdose seen with opioids while still being able to provide a comparable level of analgesia,” said Todd Bertoch, M.D., chief medical officer for pain research at CenExel and lead investigator for the ALLEVIATE-2 study. “The biggest challenge in the search for new drugs for pain has been finding something safe that can treat more severe pain that today requires use of an opioid. The level of analgesia seen across both ALLEVIATE-1 and ALLEVIATE-2 as well as the safety data that has been generated suggest that cebranopadol could fulfill this urgent need.” Additional Results From the ALLEVIATE-1 Phase 3 Trial in Patients Following Abdominoplasty Surgery Positive topline results from the ALLEVIATE-1 Phase 3 pivotal study of cebranopadol in patients for the treatment of moderate-to-severe pain following abdominoplasty surgery were announced in January 2025. These results demonstrated a large analgesic effect in the cebranopadol-treated patients compared to patients receiving placebo (see Figure 2). Furthermore, results from the ALLEVIATE-1 clinical trial demonstrated that cebranopadol-treated patients also required significantly fewer doses of rescue medication than patients receiving placebo (LS mean difference of 2.2; p<0.001). The ALLEVIATE-1 and ALLEVIATE-2 clinical studies, combined with strong safety data from several human abuse potential (HAP) studies, will be submitted to the U.S. Food and Drug Administration (FDA) as the basis for potential approval. Tris plans to submit full results from the ALLEVIATE-1 abdominoplasty and ALLEVIATE-2 bunionectomy clinical trials for presentation at an upcoming medical congress. About ALLEVIATE-1 The ALLEVIATE-1 clinical trial (NCT06545097) was a Phase 3 multicenter, randomized, double-blind, placebo-controlled study. The primary objective of ALLEVIATE-1 was to evaluate the analgesic efficacy of cebranopadol compared with placebo for the management of moderate-to-severe acute pain following full abdominoplasty as measured by pain intensity (11-point numeric rating scale) assessments. Secondary objectives included assessing the analgesic efficacy of cebranopadol through use of rescue medication, early discontinuations and subject’s overall assessment of study medication. About ALLEVIATE-2 The ALLEVIATE-2 clinical trial (NCT06423703) was a Phase 3 multicenter, randomized, double-blind, placebo-and active-controlled study. The primary objective of ALLEVIATE-2 was to evaluate the analgesic efficacy of cebranopadol compared with placebo for the management of moderate-to-severe acute pain following bunionectomy as measured by pain intensity (11-point numeric rating scale) assessments. Secondary objectives included assessing the analgesic efficacy of cebranopadol through use of rescue medication, including the need for opioid rescue medication, early discontinuations and subject’s overall assessment of study medication. About Acute Pain Acute pain affects millions of patients each year and is caused by injury, surgery, illness, trauma, burns or painful medical procedures, which can last up to three months, and typically resolves once the underlying cause is treated or healed. Moderate-to-severe acute pain can often only be effectively treated with opioid analgesics such as oxycodone, especially following joint replacements and other orthopedic procedures, invasive surgeries, and major traumas and burns. About Cebranopadol (TRN-228) Cebranopadol is a first-in-class investigational therapy that targets two key receptors, the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors (a dual-NMR agonist), for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). These receptors are partially homologous to each other, and they play both complementary and distinct roles to modulate pain biology pathways. Studied in over 33 clinical trials in more than 2,200 patients, cebranopadol’s profile has been well characterized in pain management studies. It has demonstrated positive clinical results in acute pain, chronic pain and diabetic neuropathic pain with a favorable safety profile. The FDA granted Fast Track Designation to cebranopadol for chronic low back pain, and if approved, it could become the first dual-NMR pain-relief therapy with the demonstrated ability to provide efficacy equivalent to opioids with less potential for misuse or risk of physical dependence, addiction or overdose. Cebranopadol’s novel mechanism of action has potential in treating patients with substance use disorders (SUDs). Tris plans to continue to evaluate cebranopadol’s potential to help patients break the cycle of opioid addiction. The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), has awarded Tris a five-year grant of up to $16.6 million to study cebranopadol’s potential to treat OUDs and SUDs. About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain, addiction and disorders of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @TrisPharma.