December 13, 2023, Shanghai, China—Alebund Pharmaceuticals (“Alebund” or the “Company”), an integrated biopharmaceutical company focusing on developing innovative therapies for the treatment of renal diseases and related chronic conditions, announced phase II proof-of-concept study results for the investigational drug, AP306, a first-in-class, pan-inhibitor of sodium-dependent phosphate transporters, which was discovered by Chugai Pharmaceutical Co., Ltd., and previously referred by EOS789.
In this phase II study (NCT05764590), patients on maintenance hemodialysis with hyperphosphatemia (n=55) were 1:1 randomized to AP306 or sevelamer carbonate after a washout period. Patients on AP306 followed a dose titration schedule from 75mg TID to 150mg TID per protocol during the 12-week treatment. Patients on sevelamer carbonate followed dose titration from 800mg TID per its package insert. The primary endpoint was the change in serum phosphorus from baseline to end of treatment. At the end of treatment, the effect size of serum phosphorus reduction from baseline for AP306 was clinically significant; and the response rate (defined as serum phosphorus lower than 5.5 mg/dL) in AP306 treatment arm was much higher in comparison to that in sevelamer carbonate arm. AP306 was well tolerated with no unexpected safety findings observed. Detailed results from this phase II study will be presented at an upcoming medical conference.
Dr. Sharon Moe, from the Indiana University School of Medicine, an internationally recognized researcher and key opinion leader for chronic kidney disease-mineral and bone disorder (CKD-MBD), will chair the steering committee of AP306 program, working closely with Alebund to continue its clinical development. Dr. Moe has been principal investigators for several ongoing basic and clinical research studies in the field of CKD-MBD and was the leading investigator for AP306 (EOS789) phase 1b study.
“Hyperphosphatemia remains a significant clinical problem in patients undergoing dialysis but with suboptimal control despite widespread use of phosphate binders. Treatment of AP306, a pan-inhibitor of PiT1 and PiT2 in addition to NaPi2b, achieved a higher serum phosphorus reduction with a lower pill burden than phosphate binder. Encouraged by the data from this proof-of-concept study, AP306 is promising for substantially improving phosphate control in dialysis patients with hyperphosphatemia.” said Dr. Jin Tian, Co-founder and CMO of Alebund.
“We are delighted to see the phase II data of AP306,” Dr. Gavin Xia, Co-founder, Chairman and CEO of Alebund commented, “These results strengthen our confidence that AP306 could be a novel treatment for patients with hyperphosphatemia as a single agent. With AP301 (phase III ongoing) and AP306, we have a global leading hyperphosphatemia portfolio, which will address the huge unmet needs for hyperphosphatemia management.”
About Hyperphosphatemia
Hyperphosphatemia is one of the most common complications in CKD patients. The long-term elevated serum phosphorus level could cause multiple complications such as secondary hyperparathyroidism, renal osteodystrophy and vascular calcification. It is an independent risk factor of cardiovascular events and all-cause mortalities. A good control of serum phosphorus level could effectively improve the patients’ outcome. For CKD patients undergoing dialysis treatment, the regular dialysis is not sufficient to remove the overload of serum phosphate in the body. Considering the limitations of low-phosphate diet which might cause dystrophia, oral use of phosphate binders is the prevailing treatment for hyperphosphatemia. However, less than 50% can maintain reaching a good phosphate control with current treatment options.
About the Study
NCT05764590 is a phase II randomized, open-label, active-controlled, multicenter study to evaluate the safety and serum phosphorus lowering effect of AP306 in chronic kidney disease patients receiving maintenance hemodialysis with hyperphosphatemia. The primary efficacy endpoint measures the change in serum phosphorus level from the baseline to the end of 12-week treatment or before the initiation of rescue therapy. Participants enrolled in the study were randomized in a 1:1 ratio to be treated with either AP306 or sevelamer carbonate. The study involved 11 investigational sites in China, led by Dr. Li Wang from Sichuan Provincial People’s Hospital.
About Alebund Pharmaceuticals
Alebund is a biopharmaceutical company jointly incubated by a group of industry leaders in the field of nephrology in Shanghai in 2018. Alebund focuses on the discovery and development of novel therapies primarily for kidney diseases and their complications, as well as other chronic conditions. Alebund has built a diversified and balanced pipeline of drug candidates targeting a range of renal diseases, including chronic kidney disease (CKD)/dialysis complications, IgA nephropathy, diabetic kidney disease, and autosomal dominant polycystic kidney disease (ADPKD). Alebund’s pipeline comprises both small-molecule and biological assets, in which the most advanced program is undergoing a pivotal phase III study.
About AP306
AP306 (EOS789) is an oral inhibitor of phosphate transporters, NaPi-IIb, PiT-1, PiT-2, which was discovered by Chugai Pharmaceutical Co., Ltd.. Under the option and license agreement between Alebund and Chugai in 2021, Alebund conducted the phase II study with data reported in this release. Alebund has fully executed the global rights option and now owns the global development and commercialization rights for AP306.
礼邦医药宣布首款钠依赖性磷酸盐转运蛋白泛抑制剂 AP306（EOS789）完成在透析合并高磷血症患者中的 2 期临床试验
2023 年 12 月 15 日，中国上海—礼邦医药（“礼邦”或“公司”），一家专注于开发治疗肾脏疾病及相关慢性病创新药物的综合性生物制药公司，宣布其在研药物 AP306 的 2 期概念验证性研究结果。AP306 是全球首款钠依赖性磷酸盐转运蛋白泛抑制剂，由日本中外制药发现，曾用名为 EOS789。
在这项 2 期研究（NCT05764590）中，接受维持性血液透析的高磷血症患者（n=55）在洗脱期后按 1:1 比例随机分配至 AP306 组或碳酸司维拉姆组。在 12 周治疗期间，AP306 治疗组患者按照剂量调整方案，接受 75 mg 至 150 mg 每日三次口服给药。碳酸司维拉姆治疗组患者按照其产品说明书从 800 mg 每日三次口服开始调整剂量；研究主要终点为血清磷从基线到治疗结束的变化。治疗结束时，AP306 组血清磷较基线降低幅度具有临床意义；AP306 治疗组应答率（定义为血清磷低于 5.5 mg/dL）明显高于碳酸司维拉姆治疗组。AP306 耐受性良好，未观察到非预期安全性风险。这项 2 期研究的详细结果将在未来召开的医学会议上公布。
国际公认的慢性肾病-矿物质和骨病（CKD-MBD）领域研究者和专家，印第安纳大学医学院 Sharon Moe 医生将担任 AP306 项目科学指导委员会主席，与礼邦密切合作继续 AP306 的临床开发。 Sharon Moe 医生在多项 CKD-MBD 领域进行的基础和临床研究中担任过主要研究者职务，也曾为 AP306（EOS789）1b 期研究的主要研究者。
“高磷血症仍然是透析患者面临的重要临床问题。尽管磷酸盐结合剂应用广泛，但其血磷控制效果不佳。 AP306 作为 PiT1、PiT2 及 NaPi2b 的泛抑制剂，以低于磷结合剂的剂量，实现了高于磷结合剂的降磷效果。这项概念验证性研究的数据令人鼓舞，AP306 有望大幅改善透析合并高磷血症患者的血磷控制。”礼邦联合创始人兼首席医学官田劲医生说道。
“我们非常高兴可以顺利完成 AP306 的临床 2 期研究，” 礼邦联合创始人、董事长兼首席执行官夏国尧博士评论道， “临床数据让我们对 AP306 作为小分子单一药物治疗高磷血症充满信心。与此同时，礼邦拥有全球领先的高磷血症产品组合，AP301（3 期研究正在进行中）和 AP306 未来将有巨大的潜力解决高磷血症管理方面尚未满足的临床需求。”
关于高磷血症
高磷血症是慢性肾脏病患者的最常见的并发症之一。血磷水平长期升高可导致甲状旁腺功能亢进、肾性骨病、血管钙化等多种并发症，是患者心血管事件和全因死亡的独立危险因素。控制血磷水平达标可有效改善慢性肾脏病患者预后。对于接受透析治疗的慢性肾脏病患者，即便规律透析也无法清除体内蓄积的磷酸盐。由于低磷饮食导致营养不良的限制，口服磷酸盐结合剂是目前高磷血症的主要治疗方法，但超过一半的患者通过现有治疗选择血磷仍控制不佳。
关于此项研究
NCT05764590 是一项 2 期随机、开放标签、阳性药物对照、多中心研究，旨在评估 AP306 在维持性血液透析伴高磷血症慢性肾病患者中的安全性和降血磷作用。研究的主要疗效终点是测定血清磷水平从基线到 12 周治疗结束或开始补救治疗之前的变化。该研究参与者以 1:1 比例随机接受 AP306 或碳酸司维拉姆治疗。该研究由四川省人民医院的王莉主任牵头，中国 11 家研究中心参与。
关于礼邦医药
2018 年初，礼邦医药由顶尖的肾脏病领域行业领导者孵化于中国上海，目前是一家处于临床阶段的生物制药公司，主要致力于肾脏病以及其他相关慢性疾病创新药物的发现和开发，为慢性肾脏病及相关疾病患者提供更佳临床治疗方案。礼邦医药已经建立起了丰富且均衡的肾脏病新药产品管线，包括针对慢性肾病（CKD）/透析并发症、IgA 肾病、糖尿病肾病、常染色体显性多囊肾病（ADPKD）等产品，公司在研产品包括小分子药物和生物制剂，进展最快的项目正在进行关键 3 期临床试验。
关于 AP306
AP306（EOS789）是一种口服磷酸盐转运蛋白 NaPi-IIb、PiT-1、PiT-2 抑制剂，由日本中外制药有限公司发现。根据礼邦与中外制药 2021 年签订的选择权和许可协议，礼邦完成了本新闻稿中提及的 2 期研究。礼邦已全面行使选择权，目前独家拥有 AP306 的全球开发和商业化权利。