Commercialization of a proprietary Ga-68 PSMA-targeted drug for PET imaging in recurrent prostate cancer

用于复发性前列腺癌 PET 成像的专有 Ga-68 PSMA 靶向药物的商业化

基本信息

批准号：
9916719
负责人：
David Alexoff
金额：
$ 24.84万
依托单位：
FIVE ELEVEN PHARMA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-10 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9916719
关键词：
Address Adoption Affinity Animals Area Behavior Biochemical Biological Biological Assay Cancer Patient Capromab Pendetide Caring Cause of Death Cells Chelating Agents Chemicals Chemistry Cities Clinical Clinical Protocols Clinical Research Clinical Trials Communities Consult Data Detection Development Devices Diagnostic Dose Drug Kinetics Drug Targeting Epithelial Epithelium Europe Evaluation Exhibits FOLH1 gene Formularies Formulation Funding Generations Goals High Pressure Liquid Chromatography Hour Human Image Investigation Isomerism Label Lead Legal patent Lesion Malignant Neoplasms Malignant neoplasm of prostate Measures Medical Metastatic Prostate Cancer Methods Morphology Patients Persons Pharmaceutical Preparations Phase Phase I Clinical Trials Philadelphia Positron-Emission Tomography Probability Process Production Property Prostate Adenocarcinoma Protocols documentation Published Comment Radioisotopes Radiolabeled Recurrence Recurrent disease Safety Science Screening for Prostate Cancer Site Small Business Innovation Research Grant Stress Stress Tests Testing Therapeutic Time Tissues Universities base bone imaging cancer imaging clinical care clinically significant commercialization contrast imaging design dosimetry drug sensitivity experience experimental study human data imaging agent improved outcome inhibitor/antagonist interest manufacturing process meetings men molecular imaging novel overexpression pharmacophore phase 1 study phase 2 study pre-clinical preclinical evaluation prevent prospective radiochemical radiotracer repository research clinical testing secondary outcome serum PSA specific biomarkers standard of care targeted agent targeted imaging tool treatment comparison treatment planning uptake

项目摘要

The objective of this Fast Track proposal is to support the development and commercialization of a proprietary positron emission tomography (PET) imaging agent, [68Ga]P16-093, that specifically targets prostate specific membrane antigen (PSMA) in patients with prostate cancer. Prostate cancer is the second leading cause of death from cancer in U.S. men. There are no commercially available 68Ga PSMA inhibitors on the market, which is preventing the widespread use of this clinically useful class of diagnostic drugs. The advantage of targeting PSMA using radiolabeled PSMA inhibitors is the combination of 100x–1000x fold expression levels of PSMA on the epithelium of prostate adenocarcinomas, which in combination with nM affinity constants results in uptake ratios of >50 whereas other radiotracers proposed for PCa exhibit much lower uptake ratios of the order of 5, enabling detection of much smaller lesions. Our [68Ga]P16-093 agent utilizes a proprietary chelator-linker-pharmacophore combination and has performed well in pre-clinical evaluation. Five Eleven Pharma is self-funding two Phase I clinical trials under IND #133222 to determine human dosimetry and pharmacokinetics in cancer patients using [68Ga]P16-093. Preliminary data from these trials has shown a good safety profile, favorable dosimetry and accumulation of [68Ga]P16-093 in PSMA-expressing tissue and prostate cancer lesions. During this early phase development, the FDA has suggested further investigations into the drug substance chemistry to support the longer term development of [68Ga]P16-093 and eventual NDA filing. The Phase 1 study of the Fast Track proposal is designed to validate the manufacturing process of [68Ga]P16- 093 through targeted “stress” testing, taking into account comments by the FDA addressing the identity, quantitation and stability of isomers in the final drug product. After successful completion of Fast Track Phase I, will have sufficient data to fully characterize the isomer content of the drug substance [68Ga]P16-093, including how isomer content may impact its biological activity. In Phase 2 of the Fast Track SBIR we proposes a Phase IIa clinical study that will focus on PSMA imaging in PCa patients presenting with biochemical recurrence (BCR) – rising serum PSA after primary treatment. The endpoint of the Phase IIa clinical trial is to detect a 20% change in management care in BCR patients when comparing treatment plans using [68Ga]P16-093 imaging information those based on standard of care imaging alone. This pilot efficacy data will help Five Eleven Pharma to design Phase IIb/III studies that, after consulting with the FDA, will lead to NDA-enabling clinical protocols.

这个快速提议的目的是支持专有的开发和商业化正电子发射断层扫描（PET）成像剂，[68GA] P16-093，专门针对前列腺特异性前列腺癌患者的膜抗原（PSMA）。前列腺癌是第二个主要原因美国男性癌症死亡。市场上没有市售的68GA PSMA抑制剂，这阻止了这种临床上有用的诊断药物的广泛使用。优势使用放射性标记的PSMA抑制剂靶向PSMA是100x – 1000倍倍表达水平的组合 PSMA在前列腺腺癌上皮上，与NM亲和力常数结合以> 50的摄取比为50 订单为5，可以检测到较小的病变。我们的[68GA] P16-093代理使用专有的螯合剂 - 链接 - 固定器组合，并进行了在临床前评估中很好。在IND下，五十一次制药是自筹资金的两阶段临床试验＃133222使用[68GA] P16-093确定癌症患者中的人类剂量法和药代动力学。这些试验的初步数据显示出良好的安全性，有利的剂量法和积累 [68GA]在表达PSMA的组织和前列腺癌病变中P16-093。在这一早期发展中， FDA建议进一步研究药物化学以支持长期 [68GA] P16-093和最终的NDA文件的开发。快速轨道提案的第一阶段研究旨在验证[68GA] P16-的制造过程 093通过针对FDA的评论来解决该身份的评论，最终药物中异构体的定量和稳定性。成功完成快速阶段后我将拥有足够的数据来充分表征药物的异构体含量[68GA] P16-093，包括异构体含量可能会影响其生物活性。在快速轨道SBIR的第2阶段，我们提出了一项IIA期临床研究，该研究将重点放在PSMA成像中患有生化复发（BCR）的PCA患者 - 初级治疗后血清PSA的上升。这 IIA期临床试验的终点是在BCR患者中检测到20％的管理护理变化使用[68GA] P16-093成像信息比较治疗计划独自的。此试点效率数据将帮助五个十一制药物设计IIB/III期研究，并在咨询后进行研究使用FDA，将导致增强NDA的临床方案。