Velpatasvir

BOSTON, March 19, 2025 (GLOBE NEWSWIRE) -- Atea Pharmaceuticals, Inc. (Nasdaq: AVIR) (Atea or Company), a clinical-stage biopharmaceutical company engaged in the discovery and development of oral antiviral therapeutics for serious viral diseases, today announced the poster presentation of bemnifosbuvir preclinical data at the 38th International Conference on Antiviral Research (ICAR) 2025 taking place March 17-21, 2025 in Las Vegas, Nevada. “The results presented at ICAR highlight Atea’s deep scientific expertise in antiviral drug development by demonstrating metabolism of nucleotide prodrugs, such as bemnifosbuvir, is highly cell-line dependent and cell model selection needs to be taken into account when evaluating in vitro antiviral efficacy,” said Jean-Pierre Sommadossi, PhD, Chief Executive Officer and founder of Atea. “Bemnifosbuvir is being developed in a fixed dose combination regimen with ruzasvir for the treatment of hepatitis C virus (HCV). We look forward to starting patient enrollment in the Phase 3 program evaluating this potential best-in-class HCV regimen in April.” Details for the poster presentation are as follows: Poster Number: 500 Date and Time: Tuesday, March 18, 2025, 5:30 - 7:30 PM PDT and Thursday, March 20, 2025, 8:00 - 10:00 AM PDT Title: Metabolism of Bemnifosbuvir to its Active Triphosphate Metabolite AT-9010 is Cell-Line Dependent Bemnifosbuvir (BEM), an oral prodrug of a 6-modified guanosine nucleotide analog, is a potent HCV NS5B inhibitor being developed in a fixed dose combination regimen with ruzasvir, a highly potent NS5A inhibitor for the treatment of chronic HCV infection. The activation of BEM is mediated by cellular enzymes including CatA/CES1, HINT1, ADALP1, GUK1, and NDPK to yield the intracellular active triphosphate metabolite AT-9010. In this preclinical study, the metabolism of BEM to its active triphosphate was demonstrated to be cell-line dependent, indicating that cell model selection is critical when evaluating in vitro efficacy of antiviral prodrugs such as BEM. Global Phase 3 Program for Hepatitis C Virus (HCV) Based upon a successful engagement with the US Food and Drug Administration (FDA) at the End-of-Phase 2 meeting in January 2025, Atea is initiating a global Phase 3 program and expects patient enrollment to start in April 2025. In December 2024, Atea announced that its Phase 2 study evaluating the regimen of BEM and ruzasvir for the treatment of HCV, met its primary endpoints. Atea plans to conduct two open label Phase 3 trials, one in the US and Canada and one outside of North America. Each Phase 3 trial is expected to enroll approximately 800 treatment-naïve patients, including those with and without compensated cirrhosis. For patients without cirrhosis, 8 weeks of the regimen of BEM and ruzasvir will be compared to 12 weeks of the regimen of sofosbuvir (SOF) and velpatasvir. For patients with compensated cirrhosis, 12 weeks of the regimen of BEM and ruzasvir will be compared to 12 weeks of the regimen of sofosbuvir and velpatasvir. In the US, it is estimated that more than 90% of people with HCV are non-cirrhotic. The primary endpoint for both trials encompasses sustained virologic response 12 weeks post-treatment (SVR12) in each arm and is HCV RNA < lower limit of quantitation (LLOQ) 24 weeks from the start of treatment. Measurement at 24 weeks from the start of treatment is selected to ensure the primary endpoint occurs at the same relative timepoint from start of treatment in all patients. About Bemnifosbuvir and Ruzasvir for Hepatitis C Virus (HCV) BEM has been shown in in vitro studies to be approximately 10-fold more active than SOF against a panel of laboratory strains and clinical isolates of HCV GT 1–5. In vitro studies have also demonstrated BEM remained fully active against SOF resistance-associated substitutions (S282T), with up to 58-fold more potency than SOF. The PK profile of bemnifosbuvir supports once-daily dosing for the treatment of HCV. BEM has been shown to have a low risk for drug-drug interactions. BEM has been administered to over 2,300 subjects and has been well-tolerated at doses up to 550 mg for durations up to 12 weeks in healthy subjects and patients. Ruzasvir has demonstrated highly potent and pan-genotypic antiviral activity in preclinical (picomolar range) and clinical studies. Ruzasvir has been administered to over 2,100 subjects at daily doses of up to 180 mg for 12 weeks and has demonstrated a favorable safety profile. The PK profile of ruzasvir supports once-daily dosing. About Hepatitis C Virus (HCV) HCV is a blood-borne, positive-sense, single-stranded (ss) RNA virus that primarily infects liver cells. HCV is a leading cause of chronic liver disease and liver transplants, spreading via blood transfusion, hemodialysis and needle sticks, with 242,000 deaths occurring each year. Despite the availability of direct-acting antivirals, HCV continues to be a significant global healthcare issue. An estimated 50 million people worldwide are chronically infected with HCV and there are approximately one million new infections each year. In the US, between 2.4 and 4 million people are estimated to have HCV with annual new infections outpacing treatment rates. HCV infections in the US predominate in patients in the age group between 20-49 years old, and it is estimated that less than 10% of HCV-infected patients in the US have cirrhosis. Chronic HCV infection is the leading cause of liver cancer in the US, Europe and Japan. About Atea Pharmaceuticals Atea is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral antiviral therapies to address the unmet medical needs of patients with serious viral infections. Leveraging Atea’s deep understanding of antiviral drug development, nucleos(t)ide chemistry, biology, biochemistry and virology, Atea has built a proprietary nucleos(t)ide prodrug platform to develop novel product candidates to treat single stranded ribonucleic acid, or ssRNA, viruses, which are a prevalent cause of serious viral diseases. Atea plans to continue to build its pipeline of antiviral product candidates by augmenting its nucleos(t)ide platform with other classes of antivirals that may be used in combination with its nucleos(t)ide product candidates. Our lead program and current focus is on the development of the regimen of bemnifosbuvir, a nucleotide analog polymerase inhibitor, and ruzasvir, an NS5A inhibitor, to treat HCV. For more information, please visit www.ateapharma.com. Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include but are not limited to statements regarding the development of the regimen of bemnifosbuvir and ruzasvir for the treatment of HCV, including the anticipated initiation of patient enrollment in the Phase 3 program, and the potential best in class profile of the regimen . When used herein, words including “expected,” “should,” “anticipated,” “believe.” “will,” “plans”, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Atea’s current expectations and various assumptions. Atea believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Atea may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, the timeline for the completion of the strategic alternatives review process is unknown and there can be no assurance that the process will result in any particular outcome; dependence on the success of Atea’s most advanced product candidates, in particular the combination of bemnifosbuvir and ruzasvir for the treatment of hepatitis C; as well as the other important factors discussed under the caption “Risk Factors” in Atea’s Annual Report on Form 10-K for the year ended December 31, 2024 as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SEC’s website at www.sec.gov. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While Atea may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing Atea’s views as of any date subsequent to the date of this press release. Contacts Jonae BarnesSVP, Investor Relations and Corporate Communications617-818-2985Barnes.jonae@ateapharma.com Joyce AllaireLifeSci AdvisorsJallaire@lifesciadvisors.com

关注并星标CPHI制药在线 从 MASH 失败到 PBC 逆袭：Seladelpar 的坎坷研发路 在生物医药研发的漫长进程中，诸多药物皆历经从满怀期望到遭遇挫折，再到重燃希望的曲折发展轨迹，Seladelpar便是其中具有代表性的典型案例。该药物最初由 CymaBay 公司开展研发工作，2006 年，强生公司与 CymaBay Therapeutics 达成全面开发与商业化合作协议，获得包括 Seladelpar 在内的 3 款药物授权许可，自此开启了 Seladelpar 的研发征程。 起初，Seladelpar 被预期用于治疗代谢功能障碍相关脂肪性肝炎（MASH）。然而，一项 2 期研究结果却对研发团队造成了沉重打击。研究数据表明，Seladelpar 在 MASH 治疗中的获益情况不及安慰剂，且存在潜在安全性问题。基于此，CymaBay 公司不得不终止该药物在 MASH 领域的研发工作，Seladelpar 的研发前景一度陷入困境。 随着研究的深入推进，转机出现于对其作用机制的深度挖掘。科研人员发现，Seladelpar 作为一种口服强效选择性过氧化物酶体增殖物活化受体 δ（PPARδ）激动剂，在原发性胆汁性胆管炎（PBC）治疗领域展现出巨大潜力。PPARδ 作为核受体，在调控胆汁酸代谢、炎症及纤维化进程中发挥着关键作用。Seladelpar 能够通过激活 PPARδ，有效改善胆汁淤积状况，减轻肝脏炎症和纤维化程度，进而改善 PBC 患者的症状与预后。 吉利德科学敏锐捕捉到这一潜力，于 2024 年 2 月以 43 亿美元收购 CymaBay Therapeutics，将核心管线药物 Seladelpar 纳入旗下。同年 8 月 9 日，在 Seladelpar 美国 FDA PDUFA 日期（8 月 14 日）前一周，吉利德科学再次迅速行动，以 3.2 亿美元从强生公司购得 Seladelpar 的全球特许权使用费。这一系列举措彰显出吉利德科学在原发性胆汁性胆管炎治疗领域的战略布局，也凸显其对 Seladelpar 的高度期望。 吉利德科学的判断得到了后续研究的验证。Seladelpar 在 PBC 治疗研究中展现出卓越疗效。欧盟批准 Seladelpar 上市，其依据源于关键性 RESPONSE 研究结果。该研究为一项双盲、安慰剂对照的 3 期临床试验，在全球范围内招募了 193 名参与者，旨在评估 Seladelpar 对 UDCA 一线治疗反应不充分或不耐受的成年 PBC 患者的疗效与安全性。试验过程中，受试者每日口服 10 毫克 Seladelpar 或安慰剂，针对碱性磷酸酶（ALP）及与肝功能、患者生活质量相关治疗终点展开评估。 研究结果显示，持续观察 12 个月后，接受 Seladelpar 治疗的受试者中，高达 62% 成功达到综合生化应答这一关键主要终点，而安慰剂组仅为 20%。在 ALP 值正常化方面，Seladelpar 治疗组有 25% 的受试者于第 12 个月实现，安慰剂组则无此变化。以第 6 个月与基线相比的瘙痒评分变化作为关键性次要终点考量，接受 Seladelpar 治疗的患者显示出与安慰剂相比具有统计学显著性的瘙痒减轻。这些数据充分证明了 Seladelpar 相较于安慰剂的显著优势，也为 PBC 患者带来了新的治疗希望。 PBC 患者的 “救星” 来了？ 原发性胆汁性胆管炎（PBC），这一慢性胆汁淤积性肝病，如同隐匿在患者身体里的 “定时炸弹”，给患者带来了极大的痛苦。据统计，欧洲约有 16.3 万人罹患 PBC ，且发病率呈上升态势，然而，与之形成鲜明对比的是，治疗药物的选择却极为有限。 目前，PBC 仍无法根治，患者需终身与之抗争，治疗目标主要是延缓疾病进展、减轻胆汁淤积相关症状，如胆汁性瘙痒。熊去氧胆酸（UDCA）作为 PBC 一线治疗用药，自 1998 年获美国 FDA 批准上市以来，在一定程度上能够减缓肝损伤、阻止病情恶化。但令人遗憾的是，约 40% 患者对其无应答，这意味着这些患者的疾病进展风险依然高悬，即便接受现有治疗方案，肝功能检查结果依旧异常，且瘙痒症状难以改善。 奥贝胆酸（OCA）在 2016 年获美国 FDA 批准，成为 PBC 二线治疗药物，可与 UDCA 联用治疗对 UDCA 应答不佳患者，或单药用于 UDCA 不耐受患者。但随着研究的深入，它的局限性逐渐暴露出来。其中，瘙痒问题最为突出，多项研究显示其发生率接近 60%，且具有明显剂量依赖性。从治疗效果反馈来看，约 50% 患者接受 OCA 治疗后，未能达到预期疗效。 在这样的背景下，Seladelpar 的出现，无疑给 PBC 患者带来了新的曙光。它有着独特的差异化优势，从机制上实现了胆汁淤积、炎症、瘙痒 “一药三管”。作为一种口服的强效选择性过氧化物酶体增殖物活化受体 δ（PPARδ）激动剂，Seladelpar 通过激活 PPARδ，有效调控胆汁酸代谢，改善胆汁淤积，从根源上解决胆汁流动受阻的问题；同时，它能够减轻肝脏炎症，缓解肝脏内胆管的炎症和破坏，降低肝脏损伤的风险；还能显著减轻患者的瘙痒症状，提高患者的生活质量。 在 RESPONSE 研究中，Seladelpar 治疗组在综合生化应答、ALP 值正常化以及瘙痒减轻等方面都取得了显著优于安慰剂组的成绩，这不仅证明了它的疗效，也为 PBC 患者提供了一种更有效的治疗选择，有望成为 PBC 患者的 “救星”，改写他们的治疗史。 百亿市场争夺战 随着全球对健康的重视以及医疗技术的发展，医药市场规模不断扩大，原发性胆汁性胆管炎（PBC）治疗市场也呈现出迅猛的增长态势。据相关数据统计，2017 年全球 PBC 治疗市场规模为 5.26 亿美元 ，预计未来 10 年将以 36.3% 的复合增长率攀升，到 2026 年有望达到 85.93 亿美元 ，如此巨大的市场潜力，吸引了众多药企的目光，一场激烈的市场争夺战已然拉开帷幕。 在这场争夺战中，Seladelpar 虽然凭借其独特的疗效和作用机制脱颖而出，但也面临着诸多强劲的竞争对手。Genfit 公司研发的 Elafibranor 属于 PPARα/δ 激动剂，目前其治疗 PBC 的新药上市申请已获美国 FDA 受理。GSK 公司开发的 Linerixibat 是一款口服回肠胆汁酸转运蛋白选择性抑制剂，旨在治疗 PBC 相关胆汁淤积性瘙痒，2 期研究成果表明，它有效减轻了胆汁淤积性瘙痒，且未引发严重不良事件。这些竞争对手的产品在不同方面都有着各自的优势，给 Seladelpar 的市场推广带来了不小的压力。 吉利德在肝病领域有着深厚的布局和长远的战略规划。从丙肝到 MASH 再到 PBC，吉利德不断拓展自己在肝病治疗领域的版图。在丙肝治疗方面，其研发的 Epclusa（Sofosbuvir+Velpatasvir）近乎改写丙肝治疗历史，对多种丙肝基因型治愈率颇高，疗程相对较短，副作用较小，让丙肝从一种难以治愈的疾病变成了可以被有效控制的疾病 。在乙肝治疗领域，Vemlidy（富马酸丙酚替诺福韦）表现优异，低剂量便能实现高效病毒抑制，且对肾脏和骨骼安全性更佳，为乙肝患者带来了更好的治疗选择。 在 MASH 领域，吉利德通过一系列收购与合作，构建起完整的 MASH 产品线，涵盖 TGFβ 抗体、ASK - 1 抑制剂、ACC 抑制剂和 FXR 激动剂等。即便部分 MASH 药物临床试验受挫，吉利德也未轻言放弃。如旗下 ACC 抑制剂 Firsocostat，临床试验中显著降低肝脂肪含量，部分患者肝脂肪含量降幅超 30% 。此外，吉利德还携手人工智能公司 Insitro，借助机器学习技术加速 MASH 药物研发进程，展现出其在肝病领域持续创新和进取的决心。 收购 CymaBay 获得 Seladelpar，更是吉利德在肝病领域的一次重要战略布局。Seladelpar 的上市，填补了 PBC 治疗的空白，为吉利德在肝病领域的竞争增添了有力的砝码，进一步巩固了其在罕见病治疗领域的地位。2024 年吉利德财报显示，其总营收入达 287.54 亿美元 ，其中肝病业务收入 30.21 亿美元，同比增长 9% ，肝病业务收入占总营收 10.5% ，丙肝药物索磷布韦 + 维帕他韦以及乙肝药物丙酚替诺福韦这两款药物 2024 年全年收入超 25 亿美元，Seladelpar 自 2024 年上市以来也为吉利德贡献 3000 万美元营收 ，这足以证明吉利德在肝病领域的市场影响力和盈利能力。 然而，吉利德在肝病领域的发展也并非一帆风顺，存在着一些隐忧。在激烈的市场竞争中，如何保持 Seladelpar 的竞争优势，应对其他竞争对手的挑战，是吉利德需要面对的问题。药物研发本身就充满了不确定性，虽然吉利德在肝病领域已经取得了不少成果，但未来的研发道路上仍可能面临各种困难和挫折，如研发周期延长、研发成本增加、临床试验失败等风险。市场准入和医保覆盖也是影响药物推广和销售的重要因素，如果不能顺利解决这些问题，将限制吉利德产品的市场拓展。 结语 Seladelpar 获批是肝病治疗领域重要里程碑，给原发性胆汁性胆管炎患者带来希望，助力吉利德在肝病市场竞争，是科研与人类对抗疾病的重大突破。但 PBC 治疗领域仍面临提高疗效、降低副作用、扩大药物可及性等挑战和未满足需求。未来随着科技进步和疾病机制研究深入，有望出现更多创新疗法和药物，提升患者治疗体验与生活质量。 参考来源： 1、吉利德官网 智药研习社近期会议预告 扫码领取CPHI & PMEC China 2025展会门票 来源：CPHI制药在线 声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。 投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~