Methoxy Polyethylene Glycol-Epoetin Beta

SHANGHAI, Aug. 7, 2026 /PRNewswire/ -- Alebund Pharmaceuticals (Jiangsu) Limited ("Alebund" or the "Company"; HKEX: 09637), a renal-focused biopharmaceutical company, today announced that the New Drug Application (NDA) for AP301 capsules, a novel oral iron-based phosphate binder, for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) receiving maintenance dialysis, is formally accepted for review by China's National Medical Products Administration (NMPA) today. The NDA is supported primarily by the results of RESPOND-1, the pivotal Phase III clinical trial of AP301 completed in China, together with other accumulated clinical data. AP301 is a novel fiber-iron-based phosphate binder that offers high phosphate-binding capability, does not require chewing before swallowing, does not expand in volume when exposed to gastric fluid, and is not systemically absorbed. These features contribute to a reduced pill burden, improved tolerability, and enhanced patient adherence. AP301 China Pivotal Phase III Trial (RESPOND-1) RESPOND-1 was a randomized, open-label, active-controlled, multicenter pivotal Phase III clinical trial conducted at 50 sites in China and led by Professor Li Zuo, Director of the Department of Nephrology at Peking University People's Hospital. A total of 474 patients with hyperphosphatemia receiving maintenance dialysis were randomized in a 3:1 ratio to AP301 (355 patients) or sevelamer carbonate (119 patients) for a 52-week treatment period, with doses in both groups titrated to the same serum phosphate target.[4] The trial met both of its pre-specified primary efficacy endpoints. The AP301 maintenance dose demonstrated clinically and statistically significant superiority over the ineffective low dose in reducing serum phosphate levels, and the efficacy of AP301 was robust and sustained throughout the entire 52-week treatment period, meeting the endpoint of non-inferiority to sevelamer carbonate in reducing serum phosphate levels as designed in the trial. AP301 was safe and well tolerated. The most common adverse events were discolored feces and diarrhea. Diarrhea generally occurred early in treatment and resolved without any change to treatment. At Week 12, the AP301 group was non-inferior to the active comparator sevelamer carbonate group in reducing serum phosphate levels least-squares mean reductions from baseline of 0.72 mmol/L ([2.22 mg/dL] vs. 0.70 mmol/L [2.22 mg/dL] vs. 0.70 mmol/L [2.17 mg/dL], respectively); the upper bound of the 95% confidence interval (CI) for the between-group difference (0.06 mmol/L [0.20 mg/dL]) was below the pre-defined non-inferiority margin of 0.19 mmol/L (0.59 mg/dL), demonstrating that AP301 met the pre-specified non-inferiority criterion. During the low-dose control period (from the end of Week 24 to the end of Week 27), among AP301 responders (serum phosphate <1.78 mmol/L [5.5 mg/dL] at the end of Week 20) who were re-randomized 1:1, serum phosphate control in the AP301 maintenance-dose group (94 patients) was superior to that in the AP301 ineffective low-dose control group (93 patients), with a between-group difference of -0.58 mmol/L (-1.8 mg/dL) (P<0.001), which was both clinically and statistically meaningful. At Week 52, the AP301 group showed a greater mean reduction in serum phosphate level from baseline than the sevelamer carbonate group (0.76 mmol/L [2.35 mg/dL] vs. 0.72 mmol/L [2.22 mg/dL]), a higher serum phosphate target attainment rate (66.7% vs. 58.6%), and a lower mean daily dose exposure (AP301 6.52 g/day vs. sevelamer carbonate 7.56 g/day). AP301 achieved a robust and sustained reduction in serum phosphate levels throughout the 52-week treatment period[4]. AP301 was generally safe and well tolerated over the 52-week treatment period. The most common adverse events were discolored feces and diarrhea. Diarrhea generally occurred early in treatment and resolved without any change to treatment. In addition, no notable iron-overload risk signal was observed during the 52-week treatment period. Results from RESPOND-1 were presented at the American Society of Nephrology (ASN) Kidney Week 2025.[4] Further details of the trial are available at clinicaltrials.gov under identifier NCT07030595, or at under registration number CTR20231624. Hyperphosphatemia and Unmet Medical Need Hyperphosphatemia is a common complication in patients with CKD receiving dialysis, affecting approximately 95% of patients with end-stage renal disease ("ESRD") on dialysis.[1] Chronically elevated serum phosphate is associated with vascular calcification, secondary hyperparathyroidism and renal osteodystrophy, as well as increased risks of cardiovascular events and all-cause mortality.[2] Regular dialysis and dietary phosphorus restriction are generally insufficient to adequately control the phosphate burden, and patients often require long-term pharmacological treatment. Despite the widespread use of phosphate binders, according to data from China Insights Consultancy, approximately 76% of dialysis patients in China fail to achieve the target serum phosphate range of 1.13–1.78 mmol/L [3.5–5.5 mg/dL];[1] separately, according to 2021 data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), approximately 52% and 39% of hemodialysis patients in the United States and Japan, respectively, had serum phosphate levels above 1.78 mmol/L [5.5 mg/dL].[3] Existing therapies continue to face challenges in gastrointestinal tolerability, pill burden and long-term treatment adherence, and innovative treatment options that combine efficacy, tolerability and dosing convenience remain to be further developed.[1-3] Dr. Gavin Guoyao Xia, Co-founder, Chairman of the Board, and Chief Executive Officer of Alebund Pharmaceuticals, said: "The NMPA's acceptance of the NDA for AP301 marks a key step in advancing Alebund's proprietary products from clinical development toward commercialization, and an important milestone in our global strategy. Hyperphosphatemia requires long-term management, yet reconciling efficacy, safety and adherence remains a core challenge in clinical care today. As a potential best-in-class oral phosphate binder, AP301 can genuinely offer patients with chronic kidney disease on dialysis a long-term treatment option that brings together efficacy, tolerability and dosing convenience. Building on this acceptance, we will actively support the review process and, drawing on our manufacturing base in Yangzhou, accelerate our preparations for launch. We look forward to bringing this innovation from China to patients with kidney diseases around the world." Jin Tian, M.D., Co-founder and Chief Medical Officer of Alebund Pharmaceuticals, commented: "Achieving the sustained serum phosphate control within the target range over the long term remains a major challenge for patients with chronic kidney disease on dialysis. Results from the AP301 China Phase III pivotal study confirmed that this novel iron-based phosphate binder effectively lowers phosphorus, is safe, and well tolerated. We will work closely throughout the review process and continue to advance the global clinical development of AP301, with the goal of making a new phosphate lowering product available to patients as soon as possible." About Alebund Pharmaceuticals Alebund Pharmaceuticals (09637.HK) is a biopharmaceutical company focused on kidney disease and related chronic conditions, aiming to bring better therapies to patients worldwide. It has one of the broadest renal-focused pipelines and an integrated platform spanning R&D, manufacturing and commercialization. Its portfolio comprises seven investigational drug candidates and one commercialized product, Mircera®. Three of the candidates are at the clinical stage: AP301 (Phase III; China Pivotal Phase III trial completed, global MRCT ongoing), AP306 (Phase II) and AP303 (Phase I). Together they address chronic kidney disease (CKD) and its complications, including hyperphosphatemia, renal anemia, IgA nephropathy, diabetic kidney disease, FSGS and ADPKD. Alebund has built a manufacturing site in Yangzhou, Jiangsu to support the future commercial manufacturing of AP301 and other pipeline products and has obtained a Drug Manufacturing License (Category B) issued by the Jiangsu Provincial Drug Administration. The Company has also established a dedicated nephrology sales team responsible for the commercialization of relevant products in China. For more information, visit . Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements regarding clinical development plans, expected timing of data, product potential and future development. These statements are based on the Company's judgments and assumptions as of the date of this press release and are subject to various risks and uncertainties; actual results may differ materially from such forward-looking statements. This press release does not constitute an offer to sell or a solicitation of an offer to purchase any securities. SOURCE Alebund Pharmaceuticals 21% more press release views with Request a Demo

如果懒得看，一句话总结 现有临床和机制研究均未提示PRLR（泌乳素受体）阻断会直接导致勃起功能障碍（ED）；相反，ED主要与持续性高泌乳素血症导致的下丘脑–垂体–性腺轴抑制和睾酮下降有关，而非PRLR信号被抑制本身。 摘要 泌乳素（prolactin，PRL）与雄激素之间并非简单的“升高—降低”线性关系，而是具有明显的浓度依赖性、组织特异性和性别差异。生理浓度的PRL可能参与睾丸间质细胞功能、黄体生成素受体表达及局部类固醇生成的维持；但持续性高泌乳素血症通常通过抑制下丘脑–垂体–性腺轴，降低促性腺激素脉冲及睾酮生成，导致男性低促性腺激素性性腺功能减退。在女性中，PRL异常和高雄激素血症均可引起月经紊乱、不孕、痤疮和毛发改变，因此临床表型高度重叠，但近十年的研究并不支持将高泌乳素血症视为多囊卵巢综合征本身的固有组成。与此同时，毛囊局部PRL–PRLR信号可能在不依赖循环雄激素变化的情况下调控毛周期，并与雄激素受体相关通路共同参与雄激素性脱发。总体而言，PRL更倾向于是雄激素系统的上游调节因子和局部协同信号。 一、PRL与雄激素的总体关系：双相调节 PRL主要由垂体前叶泌乳素细胞分泌，受下丘脑多巴胺持续性抑制。PRL受体属于Ⅰ型细胞因子受体家族，结合配体后主要激活JAK2–STAT5，也可联动MAPK/ERK、PI3K–AKT等通路。PRLR并不仅存在于乳腺，也表达于下丘脑、性腺、前列腺、皮肤和毛囊等组织，因此PRL既具有经典的内分泌作用，也可能通过旁分泌和自分泌方式发挥局部效应。 现有证据提示，PRL对雄激素系统具有典型的双相效应。生理或轻度升高的PRL可能对性腺具有一定支持作用，例如维持睾丸间质细胞对LH的敏感性、促进LH受体和部分类固醇合成相关蛋白表达；但PRL持续显著升高时，中枢性抑制效应占主导，最终表现为LH、FSH及睾酮降低。关于PRL直接促进睾丸类固醇生成的证据主要来自早期动物和细胞实验，而近十年人体研究更明确支持“长期高PRL导致低雄激素”的临床关系。Leydig细胞的睾酮合成仍主要由LH/LHCGR–cAMP–PKA–StAR通路控制，PRL更可能充当调节或许可性信号，而非主要的促雄激素激素。 因此，不能简单概括为“PRL越高，雄激素越低”。在生理范围内，PRL可能支持局部性腺功能；当PRL持续超出生理范围后，其对下丘脑–垂体–性腺轴的抻制逐渐成为主导，循环雄激素水平随之下降。 二、高PRL如何降低男性雄激素 高泌乳素血症导致男性低睾酮的核心机制发生在下丘脑和垂体层面。持续升高的PRL可改变下丘脑生殖神经内分泌网络，降低GnRH神经元所接受的兴奋性输入，特别是干扰kisspeptin相关信号，使GnRH脉冲频率和幅度下降。GnRH脉冲减弱后，垂体LH和FSH分泌不足，睾丸间质细胞失去足够的LH刺激，StAR介导的胆固醇转运和后续睾酮合成受到抑制。 临床上，这类患者通常表现为低睾酮伴LH和FSH偏低或“不恰当地正常”，属于低促性腺激素性性腺功能减退，而不是原发性睾丸衰竭。高PRL还可能通过降低性欲、影响中枢多巴胺能奖赏系统和勃起功能，使症状严重程度超过单纯血清睾酮下降所能解释的范围。男性患者可出现性欲减退、勃起功能障碍、精子数量和质量下降、肌肉量减少、体毛减少以及长期骨量丢失。 近年的男性泌乳素瘤研究显示，在卡麦角林治疗后，随着PRL下降和肿瘤缩小，部分患者的LH–睾酮轴可以逐步恢复。2022年的垂体腺瘤队列中，男性大腺瘤患者接受约两年卡麦角林治疗后，约六成恢复正常睾酮，但仍有一部分患者持续存在性腺功能减退。 这说明低睾酮并不完全由当时的PRL数值决定，还受到高PRL持续时间、肿瘤体积、正常垂体组织受压、年龄、肥胖及睾丸基础功能等因素影响。 2025年的研究进一步报道，少数男性存在特发性高泌乳素血症但总睾酮仍处于正常范围。这类患者经多巴胺受体激动剂治疗后，部分性功能症状仍可改善，提示PRL对男性性功能的影响并不完全由睾酮介导。 因此，在研究PRL与雄激素的相关性时，仅检测总睾酮并不充分，还应结合游离睾酮、SHBG、LH、FSH、性功能量表和精液参数。 三、雄激素是否反过来影响PRL PRL与雄激素之间也存在反向调节。临床上，睾酮治疗并不总是降低PRL，部分泌乳素瘤男性在接受睾酮替代后反而出现PRL升高或肿瘤控制变差。一个重要原因是睾酮可经芳香化酶转化为雌二醇，而雌激素能够促进垂体泌乳素细胞增殖和PRL合成。 近年来关于芳香化酶抑制剂治疗男性难治性泌乳素瘤的病例和综述支持这一机制。对于卡麦角林控制不佳、同时需要睾酮替代的男性，在加入阿那曲唑或来曲唑后，部分患者的PRL和肿瘤体积得到进一步控制。 这并不意味着睾酮本身直接刺激PRL，而是提示睾酮–雌二醇转换可能构成PRL调节的重要中间环节。 由此可见，雄激素对PRL的影响取决于芳香化程度、脂肪组织含量、雌二醇水平及泌乳素瘤细胞对雌激素的敏感性。肥胖男性由于脂肪组织芳香化酶活性较高，理论上更容易出现睾酮替代后雌二醇升高，因此在泌乳素瘤患者中使用睾酮时，应同步监测PRL、睾酮、雌二醇和肿瘤影像，而不能只观察低睾酮症状是否改善。 四、女性中的PRL与高雄激素：PCOS关系需要重新认识 女性高PRL和高雄激素状态存在明显的临床表型重叠。两者均可造成月经稀发或闭经、不排卵、不孕、痤疮及毛发改变，因此过去常认为PCOS可能伴随“功能性高PRL”。然而，近十年的严格研究越来越不支持这一观点。 2019年的综述指出，过去PCOS合并高PRL的研究常未充分排除抽血应激、妊娠、甲状腺功能减退、药物影响、宏泌乳素血症以及垂体病变。在进行重复检测和规范病因学评估后，多数所谓“PCOS相关高PRL”可由其他原因解释，并没有充分证据证明PCOS本身会导致持续性高泌乳素血症。 但2022年的观察性研究荟萃分析得出了不同方向的统计结果：汇总部分研究后，PCOS女性的平均PRL水平高于对照，差异在某些亚组中仍然存在。 与此同时，另一些大型队列和综述又发现，PCOS患者的PRL可能低于对照，并提出较低PRL与胰岛素抵抗、肥胖和代谢风险相关。 这些看似矛盾的结果说明，PRL与PCOS或高雄激素血症之间可能不是单一方向关系。PCOS本身具有高度异质性，不同患者可分别以卵巢高雄激素、肾上腺高雄激素、胰岛素抵抗、肥胖或排卵障碍为主。PRL水平还容易受到抽血时间、精神应激、睡眠、药物、雌激素、甲状腺功能及宏泌乳素的影响。因此，PCOS人群中的轻度PRL差异很难直接解释为雄激素所致。 更合理的临床结论是：持续高PRL不应被简单归因于PCOS。对于高雄激素女性发现PRL升高，应按照独立的高泌乳素血症进行重复检测和病因排查，包括排除妊娠、药物、甲状腺功能减退、肾功能异常、宏泌乳素血症及垂体病变。 五、PRL是否直接促进女性雄激素生成 从理论上看，PRL可能在卵巢和肾上腺层面对雄激素生成产生调节作用。卵巢颗粒细胞、卵泡膜细胞及黄体组织均可表达PRLR，PRL信号能够与LH、胰岛素和IGF相关通路交叉。然而，目前人体研究尚不能证明适度PRL升高会稳定、直接地增加睾酮或雄烯二酮。 在明显高泌乳素血症中，最终临床表现通常仍是GnRH及促性腺激素受到抑制，卵巢排卵和雌激素生成下降，而不是典型的持续高雄激素状态。部分女性虽然出现痤疮或多毛，但可能与雌激素下降后雄激素相对作用增强、SHBG变化、肾上腺雄激素改变，或合并PCOS有关，并不一定代表PRL直接刺激了大量雄激素合成。 因此，高PRL女性出现“雄激素样表现”时，应区分三种情况：真正的生化高雄激素血症、雌激素降低造成的相对雄激素优势，以及PRL和PCOS等两种独立疾病并存。仅凭痤疮、多毛或脱发不能推断PRL促进了雄激素生成。 六、PRL、雄激素与雄激素性脱发 雄激素性脱发（androgenetic alopecia，AGA）的经典核心机制是毛囊局部雄激素敏感性增强。睾酮在毛囊中经5α还原酶转化为双氢睾酮（DHT），DHT与雄激素受体结合后，引起真皮乳头细胞转录程序改变，导致毛发生长期缩短、终末毛逐渐微小化以及生长期毛囊比例下降。AGA患者的循环睾酮并不一定升高，关键在于毛囊局部DHT生成、雄激素受体表达和遗传易感性。 近十年的研究使PRL成为AGA领域的新型非雄激素靶点。人毛囊能够表达PRL和PRLR，提示毛囊内部存在局部PRL旁分泌或自分泌系统。现有实验研究认为，PRL–PRLR信号可能促进毛囊由生长期向退行期或休止期转换，延长毛囊静止状态，并抑制毛干生成。2025年的毛发药物研发综述将PRLR阻断列为促进休止期毛囊重新进入生长期的潜在策略。 值得注意的是，PRL通路与雄激素通路可能是“平行且交叉”的，而非PRL通过升高血清DHT才引起脱发。AGA的雄激素易感毛囊首先受到DHT–AR驱动，随后可能通过TGF-β、DKK1、氧化应激、炎症及毛囊干细胞静止等下游机制发生微小化；PRL–PRLR则可能进一步稳定休止期状态或限制毛囊重新进入生长期。2024年的抗体药物综述将PRLR、IL-6R、CXCL12及DKK1等共同列为AGA潜在抗体靶点，反映了AGA研发正在从单纯抑制雄激素，转向调控毛囊微环境和毛周期。 这一机制也解释了为什么阻断PRLR可能在不显著降低循环睾酮或DHT的情况下促进生发。换言之，PRLR拮抗剂不是传统意义上的抗雄激素药，而更接近一种毛周期解除抑制剂。它可能适用于雄激素信号已经触发毛囊微小化，但单纯抑制DHT不足以使休止毛囊重新进入生长期的阶段。 目前已有企业报告PRLR拮抗抗体在AGA早期临床研究中观察到毛发生长信号，但公开同行评议的完整临床数据仍较有限，因此尚不能确定其疗效大小、适用人群以及与非那雄胺、度他雄胺或米诺地尔联合使用的增益。 在证据等级上，PRL–PRLR与AGA的机制依据已较为充分，但临床有效性仍处于验证阶段。 七、PRL与雄激素相关性研究为何经常得出不同结论 首先，PRL具有明显的脉冲性和应激敏感性。睡眠、运动、性生活、乳头刺激、疼痛以及静脉穿刺焦虑均可使PRL短暂升高。单次抽血得到的轻度升高，未必代表持续性高泌乳素血症。 其次，血清总睾酮并不能完整反映雄激素生物活性。肥胖、胰岛素抵抗、甲状腺和肝脏状态均可改变SHBG。如果PRL与代谢状态同时相关，仅比较PRL和总睾酮可能产生混杂。较理想的研究应同时测定总睾酮、SHBG、计算或直接测定游离睾酮，并根据研究目的加入DHT、雄烯二酮和DHEAS。 再次，PRL与雄激素可能存在非线性关系。生理PRL、轻度升高和显著升高的生物学作用并不相同。如果研究将所有PRL水平按连续变量处理，可能掩盖低PRL、生理PRL和高PRL之间的U形或倒U形关系。 此外，血清PRL不等同于组织局部PRL活性。毛囊、前列腺及生殖组织可能存在局部PRL生成和PRLR表达变化。血清PRL正常并不能排除组织PRLR信号增强，这一点对于AGA等局部疾病尤其重要。 最后，疾病持续时间和肿瘤压迫也会影响结果。泌乳素瘤患者的低睾酮既可能来自PRL对GnRH的功能性抑制，也可能来自肿瘤压迫正常垂体组织。前者在PRL恢复后较容易逆转，后者则可能持续存在。 八、近十年证据的综合判断 综合2016年至2026年的研究，可以形成以下认识。 在男性系统性内分泌层面，持续高PRL与睾酮降低之间存在较明确的负向关系，其主要机制是下丘脑–垂体–性腺轴抑制，而不是PRL直接破坏睾丸。PRL正常化后，睾酮经常恢复，但恢复并非必然，尤其是病程较长、肿瘤较大或存在垂体组织损伤的患者。 在生理范围内，PRL可能对Leydig细胞及局部类固醇生成具有支持作用，但这部分证据以动物和细胞研究为主，尚不能据此认为提高PRL可以增加人体睾酮。 在女性中，PRL与雄激素之间不存在稳定一致的相关方向。PCOS患者既有PRL略高的研究，也有PRL偏低的研究。持续高PRL应被视为需要独立评估的问题，而不是PCOS或高雄激素血症的自然组成。 在AGA中，PRL–PRLR通路可能与DHT–AR通路并行作用。雄激素主要决定毛囊易感性和微小化启动，而PRL可能参与毛周期停止、生长期缩短及休止毛囊维持。PRLR阻断因此可能在不改变全身雄激素水平的情况下产生生发作用。 结论 PRL与雄激素的关系具有明显的层级性。系统性高PRL主要通过抑制GnRH–LH/FSH通路降低睾酮；生理PRL可能对性腺类固醇生成具有许可性支持；雄激素又可通过芳香化为雌二醇反向影响PRL分泌。在女性PCOS中，两者的关系高度异质，不能将高PRL简单解释为高雄激素的伴随现象。在AGA中，PRL更可能作为独立于循环雄激素水平的局部毛周期调节信号，与DHT–AR通路共同决定毛囊是否持续微小化和停留于休止期。 生理PRL可能支持雄激素生成，病理性高PRL通常抑制全身雄激素轴；在毛囊等外周组织中，PRL又可在不改变血清雄激素的情况下，与雄激素通路协同影响组织表型。 近十年重点参考文献 Torner L. 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