Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced results from its Phase 2 study of suzetrigine, an investigational, oral, highly selective NaV1.8 pain signal inhibitor in people with painful lumbosacral radiculopathy (LSR). The study met its primary endpoint with statistically significant and clinically meaningful reduction in pain on the numeric pain rating scale (NPRS)..

Vertex Pharmaceuticals Incorporated（Nasdaq:VRTX）今天宣布了其对suzetrigine的2期研究结果，suzetrigine是一种用于腰骶神经根痛患者的研究性口服高选择性NaV1.8疼痛信号抑制剂。该研究在数字疼痛评定量表（NPRS）上达到了其主要终点，具有统计学意义和临床意义的疼痛减轻。。

Efficacy Results

疗效结果

The study’s primary endpoint was a within-group change from baseline in the weekly average of daily leg pain intensity on the NPRS at Week 12. This 11-point scale ranges from 0 (no pain) to 10 (worst pain imaginable).

该研究的主要终点是在第12周时，NPRS上每日腿部疼痛强度的周平均值与基线相比的组内变化。这个11分制的范围从0（无疼痛）到10（可想象的最严重疼痛）。

The suzetrigine arm showed a statistically significant and clinically meaningful within-group reduction from baseline in pain with a mean change in NPRS at Week 12 of -2.02.

suzetrigine组在疼痛中显示出从基线开始的统计学显着且具有临床意义的组内减少，在第12周时NPR的平均变化为-2.02。

The study also included a placebo reference arm which showed a similar within-group reduction from baseline in pain with a mean change in NPRS at Week 12 of -1.98. The study was not designed nor powered for statistical comparison between suzetrigine and placebo.

该研究还包括一个安慰剂对照组，该组疼痛程度与基线相似，第12周的NPR平均变化为-1.98。这项研究的设计和功能都不适用于suzetrigine和安慰剂之间的统计比较。

Secondary and other endpoints were consistent with the study’s primary endpoint.

次要终点和其他终点与研究的主要终点一致。

Vertex also conducted post-hoc analyses to further evaluate the efficacy results. These showed that there was variability in the placebo response across study sites, a recognized issue in pain trials. In the ~40% of sites that had lower placebo responses, the suzetrigine arm within-group reduction in pain was similar to the overall study and had greater separation from the placebo arm.

Vertex还进行了事后分析，以进一步评估疗效结果。这些表明，不同研究地点的安慰剂反应存在差异，这是疼痛试验中公认的问题。在约40%的安慰剂反应较低的部位，suzetrigine组内疼痛减轻与整体研究相似，并且与安慰剂组有较大的分离。

These analyses suggest that trial design innovation may better control the placebo response and separate the treatment effect of suzetrigine from placebo in future studies, which Vertex will incorporate as it designs the pivotal program..

这些分析表明，试验设计创新可能会更好地控制安慰剂反应，并在未来的研究中将suzetrigine的治疗效果与安慰剂分开，Vertex将在设计关键程序时纳入研究。。

Safety Results

安全结果

Suzetrigine was generally well tolerated in the study. The incidence of adverse events (AEs) was 22.9% in the suzetrigine arm and 32.4% in the placebo arm. In both treatment arms, most AEs were mild to moderate. There were no serious adverse events (SAEs) related or possibly related to suzetrigine. There were no AEs leading to treatment discontinuation in patients treated with suzetrigine..

Suzetrigine在研究中通常耐受性良好。。在两个治疗组中，大多数AE为轻度至中度。没有与suzetrigine相关或可能相关的严重不良事件（SAE）。在接受suzetrigine治疗的患者中，没有AE导致治疗中断。。

“Suzetrigine has again demonstrated its potential to fill an important unmet need in the treatment of pain. Today's LSR results are consistent with previous studies of this pain signal inhibitor in terms of showing a meaningful treatment effect across pain conditions and a favorable safety profile,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex.

“Suzetrigine再次证明了它在满足治疗疼痛这一尚未满足的重要需求方面的潜力。Vertex 公司全球药品开发与医疗事务执行副总裁兼首席医疗官、医学博士 Carmen Bozic 说："今天的 LSR 结果与之前对这种疼痛信号抑制剂的研究结果一致，即在各种疼痛情况下都显示出显著的治疗效果和良好的安全性。

“We did not see separation between the suzetrigine and the placebo arms. Yet our post-hoc analyses suggest that this could be due to the high placebo response in this study. We remain committed to studying LSR and innovating our Phase 3 study design to control for the placebo effect as we advance suzetrigine into pivotal development for this condition.”.

“我们没有看到suzetrigine和安慰剂组之间的分离。但我们的事后分析表明，这可能是由于本研究中安慰剂的高反应。我们仍然致力于研究LSR并创新我们的3期研究设计，以控制安慰剂效应，因为我们将suzetrigine推进这种情况的关键发展。”。

“The suzetrigine Phase 2 results clearly show reduced pain intensity from baseline in the active drug arm, and the potential for suzetrigine to fill an unmet need in relieving LSR pain, a heterogeneous condition that is notoriously difficult to treat,” said Christine Sang, M.D., M.P.H., FASA, Director, Translational Pain Research, Brigham and Women's Hospital, Associate Professor of Anesthesia, Harvard Medical School, co-chair of Vertex’s Peripheral Neuropathic Pain steering committee, and lead principal investigator on the study.

“suzetrigine 2期研究结果清楚地表明，活性药物组的疼痛强度从基线水平降低，并且suzetrigine有可能满足缓解LSR疼痛的未满足需求，LSR疼痛是一种众所周知难以治疗的异质性疾病，”Brigham and Women's Hospital转化疼痛研究主任、哈佛医学院麻醉副教授、Vertex周围神经性疼痛指导委员会联合主席、该研究首席首席研究员Christine Sang说。

“Managing the placebo response in pain trials is a complex challenge. We look forward to innovating in clinical trial design, including for the pivotal study, with the aim of bringing a potentially safe and effective treatment to patients suffering from LSR.'.

“管理疼痛试验中的安慰剂反应是一项复杂的挑战。我们期待着在临床试验设计方面进行创新，包括关键研究，旨在为患有LSR的患者带来潜在的安全有效治疗。”。

Next Steps for the Pain Portfolio

疼痛组合的下一步

Neuropathic Pain

神经性疼痛

Vertex plans to advance suzetrigine into pivotal development for painful LSR following discussions with regulators on the study design and regulatory package. The company will apply learnings from analysis of the full Phase 2 data set and post-hoc analyses to inform the Phase 3 study design.

Vertex计划在与监管机构讨论研究设计和监管方案后，将suzetrigine推进痛苦LSR的关键开发。。

Earlier this year, Vertex initiated its suzetrigine pivotal program in painful diabetic peripheral neuropathy (DPN), another type of peripheral neuropathic pain (PNP). That study is ongoing.

今年早些时候，Vertex启动了其suzetrigine关键项目，用于治疗疼痛性糖尿病周围神经病变（DPN），这是另一种周围神经性疼痛（PNP）。这项研究正在进行中。

Acute Pain

急性疼痛

Additionally, as previously announced, suzetrigine is under FDA review for the treatment of moderate-to-severe acute pain. The agency granted priority review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2025.

此外，如前所述，suzetrigine正在接受FDA审查，用于治疗中度至重度急性疼痛。该机构批准了优先审查，并指定了《处方药用户费用法案》（PDUFA）的目标行动日期为2025年1月30日。

In line with its portfolio strategy, Vertex continues to advance preclinical and clinical development of additional NaV1.8 and NaV1.7 inhibitors, for use alone or in combination, in acute and neuropathic pain.

根据其投资组合策略，Vertex继续推进额外的NaV1.8和NaV1.7抑制剂的临床前和临床开发，用于单独或联合使用，用于急性和神经性疼痛。

About the Phase 2 Suzetrigine Lumbosacral Radiculopathy (LSR) Study

关于2期Suzetrigine腰骶神经根病（LSR）研究

This phase 2, 12-week, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of suzetrigine in treating patients with painful LSR. A total of 218 patients were enrolled in the study and randomized 1:1 with suzetrigine or placebo. The primary endpoint was the within-group change from baseline in the weekly average of daily leg pain intensity on a numeric pain rating scale (NPRS) at Week 12.

这项为期2、12周的随机、双盲、安慰剂对照研究评估了suzetrigine治疗疼痛性LSR患者的疗效和安全性。共有218名患者参加了这项研究，并以1:1的比例随机分配了suzetrigine或安慰剂。主要终点是第12周时数字疼痛评定量表（NPRS）上每日腿部疼痛强度的周平均值与基线的组内变化。

The study also included a placebo reference arm; however, the study was not designed nor powered for comparison between suzetrigine and placebo..

该研究还包括安慰剂参考组；然而，这项研究并不是为了比较suzetrigine和安慰剂而设计的。。

Secondary endpoints assessed the within-group change from baseline in the weekly average of the daily sleep interference scale at Week 12 and safety and tolerability. By blocking the pain signal from the peripheral sensory neurons, Vertex believes that suzetrigine may alleviate the suffering for millions of patients with painful LSR..

次要终点评估了第12周时每日睡眠干扰量表的周平均值与基线相比的组内变化以及安全性和耐受性。Vertex 公司相信，通过阻断来自外周感觉神经元的疼痛信号，suzetrigine 可以减轻数百万 LSR 疼痛患者的痛苦。

About Painful Lumbosacral Radiculopathy (LSR)

关于疼痛性腰骶神经根病（LSR）

Painful lumbosacral radiculopathy, or LSR, is one of the most common causes of peripheral neuropathic pain. It is pain caused by impairment of nerve roots in the area of the lumbar spine. It often results in radiating pain along the distribution of the impacted nerve in the body, and patients can experience back and leg pain, sensory issues or motor dysfunction.

疼痛性腰骶神经根病（LSR）是周围神经性疼痛的最常见原因之一。它是由腰椎区域神经根受损引起的疼痛。它通常会导致沿着受累神经在体内的分布放射疼痛，患者可能会经历背部和腿部疼痛，感觉问题或运动功能障碍。

Common causes of LSR include nerve compression from a herniated disk, or arthritic or degenerative changes in the area of the lower spine. LSR is a neuropathic pain condition because the impacted nerve roots are part of the peripheral nervous system and not part of the spinal cord. Millions of patients suffer from pain due to LSR every year..

LSR的常见原因包括椎间盘突出引起的神经压迫，或下脊柱区域的关节炎或退行性改变。LSR是一种神经性疼痛，因为受影响的神经根是周围神经系统的一部分，而不是脊髓的一部分。每年有数百万患者因LSR而遭受疼痛。。

About Suzetrigine

关于Suzetrigine

Suzetrigine is an investigational oral, highly selective pain signal inhibitor that is selective for NaV1.8 relative to other NaV channels. NaV1.8 is a voltage-gated sodium channel that is selectively expressed in peripheral pain-sensing neurons (nociceptors), where its role is to transmit pain signals (action potentials).

Suzetrigine是一种研究性口服高选择性疼痛信号抑制剂，相对于其他NaV通道对NaV1.8具有选择性。NaV1.8是一种电压门控钠通道，在外周疼痛感应神经元（伤害感受器）中选择性表达，其作用是传递疼痛信号（动作电位）。

Vertex’s approach is to selectively inhibit NaV1.8 using small molecules with the objective of creating a new class of pain signal inhibitors that have the potential to provide effective relief of pain without the limitations of currently available therapies, including the addictive potential of opioids.

Vertex 的方法是使用小分子选择性抑制 NaV1.8，目的是创造一类新型疼痛信号抑制剂，这种抑制剂有可能有效缓解疼痛，而不会受到现有疗法的限制，包括阿片类药物的成瘾性。

Suzetrigine has demonstrated a favorable benefit/risk profile in multiple Phase 2 and Phase 3 studies in patients with moderate-to-severe acute pain and has been granted FDA Fast Track and Breakthrough Therapy designations in moderate-to-severe acute pain in the U.S. It is currently under priority review by the FDA for the treatment of moderate-to-severe acute pain with a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2025.

Suzetrigine在中度至重度急性疼痛患者的多个2期和3期研究中表现出良好的益处/风险特征，并已被美国食品和药物管理局（FDA）授予中度至重度急性疼痛快速通道和突破性治疗指定。目前，FDA正在优先审查中重度急性疼痛的治疗，处方药使用者费用法案（PDUFA）的目标行动日期为2025年1月30日。

The Phase 3 pivotal program for suzetrigine in patients with painful diabetic peripheral neuropathy is ongoing, and the company plans to advance its pivotal program evaluating suzetrigine in patients with painful lumbosacral radiculopathy pending discussions with regulators. Suzetrigine is investigational and has not been approved by any health authority..

suzetrigine治疗疼痛性糖尿病周围神经病变患者的3期关键计划正在进行中，该公司计划在与监管机构讨论之前，推进其评估suzetrigine治疗疼痛性腰骶神经根病患者的关键计划。Suzetrigine正在进行研究，尚未获得任何卫生部门的批准。。

About Vertex

关于Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases.

Vertex是一家全球生物技术公司，投资于科学创新，为患有严重疾病的人创造变革性药物。该公司已批准用于治疗多种慢性，缩短寿命的遗传疾病的根本原因的药物-囊性纤维化，镰状细胞病和输血依赖性β地中海贫血-并继续推进这些疾病的临床和研究计划。

Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1..

Vertex还在其他严重疾病的一系列模式中拥有强大的临床研究治疗渠道，对因果人类生物学有深入的了解，包括急性和神经性疼痛，APOL1介导的肾脏疾病，IgA肾病，原发性膜性肾病，常染色体显性多囊肾病，1型糖尿病和1型强直性营养不良。。

Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 15 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For.

Vertex成立于1989年，全球总部位于波士顿，国际总部位于伦敦。此外，该公司在北美、欧洲、澳大利亚、拉丁美洲和中东设有研发基地和商业办事处。Vertex一直被公认为行业最佳工作地点之一，包括连续15年入选《科学》杂志的最佳雇主名单，以及《财富》杂志的100家最佳工作公司之一。