FDA加速批准泌尿道上皮癌新药Jelmyto上市
2020年4月15日，美国FDA加速批准以色列UroGen Pharma的Jelmyto（丝裂霉素/无菌水凝胶，Mitomycin）（研发代号UGN-101）用于治疗低危上尿路上皮癌（LG UTUC，low-grade upper tract urothelial cancer）。Jelmyto成为首个治疗低危UTUC患者的非手术疗法。
上尿路上皮癌（UTUC）指发生于肾盂及输尿管的尿路上皮恶性肿瘤，在泌尿系肿瘤中相对少见，约占肾肿瘤5%-7%，约占全部尿路上皮肿瘤5%。上尿路上皮癌可以阻塞输尿管或肾脏，导致患者出现肿胀、感染和肾功能损害。
低危UTUC指单发病灶、肿瘤＜2 cm、尿脱落细胞学发现低级别尿路上皮细胞癌（UC）、计算机断层扫描尿路造影（CTU）表现为非侵袭性肿瘤。
低危UTUC是一种罕见肿瘤，在美国每年大约有 6000-8000 名新确诊患者。
Jelmyto的有效成分丝裂霉素是一种烷基化抗肿瘤药物，能够抑制DNA转录为RNA，停止蛋白质合成，抑制癌细胞的增殖能力。此前曾获美国FDA授予的快速通道资格、孤儿药资格、优先审评资格以及突破性疗法资格认定。
丝裂霉素结构式
Jelmyto（pyelocalyceal solution）利用标准输尿管导管输送至患者病灶处，让尿路组织能够长期暴露在丝裂霉素的作用之下，从而实现非手术方法消除肿瘤。
FDA对Jelmyto的批准是基于一项OLYMPUS关键3期临床试验（NCT02793128）。该临床试验纳入了74名患者，每周接受一次Jelmyto滴注治疗，采用原发性疾病评估（PDE）方式，确定研究的主要终点：完全缓解（CR，Complete response）。患者每周接受一次Jelmyto治疗，持续六周，如果评估为完全缓解，则每月接受一次治疗，最多可再持续11个月。
本次临床试验结果显示，每周接受一次Jelmyto治疗，持续六周后，低危UTUC的完全缓解的患者为41名，完全缓解率为58％。其中达到完全缓解的19名患者（19/41）在12个月后效果仍然维持。
新闻原文：
PRINCETON, N.J.--Apr. 15, 2020-- UroGen Pharma Ltd. (Nasdaq: URGN) today announced the U.S. Food and Drug Administration (FDA) granted expedited approval for Jelmyto™(mitomycin) for pyelocalyceal solution, a first-in-class treatment indicated for adults with low-grade upper tract urothelial cancer (LG UTUC). This landmark approval is based on positive results from the Phase 3 OLYMPUS trial that showed Jelmyto provides an effective, kidney-sparing option for patients with this rare and difficult-to-treat cancer.
Jelmyto consists of mitomycin, an established chemotherapy, and sterile hydrogel, using UroGen’s proprietary sustained release RTGel™ technology. It has been designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means.
“UroGen was founded on the vision to improve lives by challenging the current standard of care. Jelmyto, which leverages our innovative technology and expertise in specialty cancers and urologic diseases, is just the beginning as we build a company focused on bringing novel solutions to patients,” said Liz Barrett, President and Chief Executive Officer, UroGen. “We thank the patients and researchers involved in our OLYMPUS trial for helping us advance a transformative treatment in a disease space that has been historically ignored. We are tremendously proud to have pioneered this first-in-class therapy that improves patient care in a difficult-to-treat cancer.”
LG UTUC is a rare cancer that develops in the lining of the upper urinary tract, ureters and kidneys. In the U.S., there are approximately 6,000 - 7,000 new or recurrent LG UTUC patients annually. It is a challenging condition to treat due to the complex anatomy of the urinary tract system. The current standard of care includes multiple surgeries and most patients require a radical nephroureterectomy, which includes the removal of the renal pelvis, kidney, ureter and bladder cuff.1 Treatment is further complicated by the fact that LG UTUC is most commonly diagnosed in patients over 70 years of age, who may already have compromised kidney functionality and may suffer further complications as a result of major surgery.
“Jelmyto offers a new, non-surgical treatment approach for patients who otherwise may require treatment by radical nephroureterectomy, which is associated with declining kidney function and other complications,” said Dr. Seth Lerner, M.D., FACS, Professor of Urology at Baylor College of Medicine in Houston, TX and Principal Investigator of the OLYMPUS trial. “This novel, minimally invasive, kidney-sparing treatment has the potential to transform the way low-grade upper tract urothelial cancer is treated and help patients avoid long-term complications associated with surgery and the loss of their kidney.”
The FDA approval is based on results from the Phase 3 OLYMPUS trial showing Jelmyto achieved clinically significant disease eradication in adults with LG UTUC.Findings include:
Complete response (CR) (primary endpoint) of 58% in the intent-to-treat population and in the sub-population of patients who were deemed not capable of surgical removal at diagnosis.
At the 12-month time point for assessment of durability, 19 patients remained in CR, seven had experienced recurrence of disease and nine patients continued to be followed for the 12-month duration of response.
Kaplan-Meier analysis estimated 12-month durability at 84%2 (based on interim data).
The most commonly reported adverse events (≥ 20%) were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Most adverse events were mild to moderate and manageable using well established treatments. No treatment-related deaths occurred.
“There has been little progress for decades in the treatment of low-grade upper tract urothelial cancer, and this new option is paradigm-shifting for patients who often face recurrence and major surgery to remove their kidney,” said Andrea Maddox-Smith, Chief Executive Officer, Bladder Cancer Advocacy Network. “We applaud the FDA approval and the impact it will have for this community of elderly patients, many of whom struggle with comorbidities and have been hoping for a surgery-free treatment option.”
UroGen is committed to helping patients access Jelmyto. UroGen Support may help identify appropriate financial assistance programs for patients with commercial, Medicare or Medicaid coverage, as well as those with no insurance coverage. These programs are for eligible patients who have been prescribed Jelmyto and who need help managing the cost of treatment. The appropriate program will depend on the patient’s coverage. Visit http://www.Jelmyto.com or contact UroGen Support at 855-JELMYTO for additional information.
The FDA evaluated Jelmyto under Priority Review, which is reserved for medicines that may represent significant improvements in safety or efficacy in treating serious conditions. Jelmyto was also granted Breakthrough Therapy designation by the FDA, which was created to expedite the development and review of drugs developed for serious or life-threatening conditions with high unmet need.
参考：
NMPA/CDE/FDA；
药融圈数据；
相关公司公开披露；
https://www.urogen.com/；
https://investors.urogen.com/news-releases/news-release-details/urogen-pharma-receives-us-fda-expedited-approval-jelmytotm-first；
https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-treatment-low-grade-upper-tract-urothelial-cancer；
https://www.drugs.com/nda/ugn_101_191219.html；等等。
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