Long-term survival data for Jelmyto, a new drug for low-grade upper urothelial carcinoma, has been released.
Low-level upper urothelial carcinoma (LG-UTUC) is a rare disease with limited treatment options available. Although significant progress has been made in endoscopic therapy, most patients still need to undergo radical nephrectomy. Analysis data from the population level show that as many as 70% of patients with low-level non-invasive diseases still have to undergo more resection operations. Long-term data from the Phase 3 Olympus trial announced during the 2021 annual meeting of the American Association of Urology (AUA) show that the use of the new drug Jelmyto to treat induced therapy in LG-UTUC patients can obtain a long-lasting response.
Jelmyto's latest treatment data
Advances in endoscopic surgery have yielded some benefits in preserving the kidney. However, a pooled analysis of 597 patients (78% of whom had low- or intermediate-grade disease) showed that 65% of patients experienced disease recurrence after ureteroscopic treatment at a median follow-up of 43 months (range 24–58). Therefore, researchers initiated the phase 3 OLYMPUS trial (NCT02793128) to evaluate Jelmyto.
This open-label single-arm phase 3 trial recruited a total of 71 LG-UTUC patients who had never received treatment, or patients with recurrent low-grade, non-invasive diseases and at least one measurable papillary tumor. Study participants received Jelmyto treatment once a week for a period of 6 weeks, followed by a grace period of 4 to 6 weeks. During this period, patients were evaluated as the main efficacy endpoint–CR rate during the primary disease assessment (PDE). If the patient's treatment results are good, they will continue to receive gel treatment every month, which can be extended for up to 11 months.
A key secondary endpoint of the trial was the durable response at 12-month follow-up, and other endpoints included the durable response to Jelmyto at 3, 6, and 9 months after the PDE visit. As part of the long-term follow-up, the researchers checked the duration of response, disease recurrence, disease progress, and death. The main analysis of the trial was conducted on the population of intentional therapy (ITT), including patients who have received one or more gel perfusions. The secondary analysis was conducted for patients who obtained CR during the PDE examination, while the long-term follow-up analysis was conducted for those patients who obtained CR within 12 months after receiving the PDE examination.
Of the 71 patients enrolled in the study (ITT population), 10 discontinued Jelmyto treatment (9 due to adverse events [AEs], 1 due to withdrawal of consent), and 19 did not achieve complete remission (CR) at the PDE visit. A total of 42 patients in the ITT population achieved treatment efficacy at the PDE visit, implying a CR rate of 59.2% (95% CI, 46.8%–70.7%). Of these patients, 1 withdrew consent, 10 discontinued treatment, and 8 experienced disease relapse.
23 patients maintained CR within 12 months, and the conversion rate to CR was 56.1% (95% CI, 39.7%-71.5%). Among them, the hospital where 5 patients were located has not yet initiated a follow-up program, 2 patients have no data available, and 1 patient has lost the follow-up. At the 2021 AUA annual meeting, Chamie shared data on the remaining 15 evaluable patients.
As of March 4, 2021, among 15 evaluable patients, the median time to response (DOR) for Jelmyto induction therapy was 28.1 months (95% CI, 14.6–37.1). 80% of patients (n = 12) experienced a durable response, defined as no evidence of recurrence or no need for radical nephrectomy. 20% of patients (n = 3) did not experience a durable response due to disease recurrence (13%; n = 2). One patient required radical nephrectomy (7%); however, it is noteworthy that this was due to ureteral stricture rather than disease recurrence. Patients experiencing recurrence underwent endoscopic ablation. None of the patients with disease recurrence developed high-grade disease. At the last follow-up, disease-specific survival was 100%.
A collection analysis of previous publications showed that the recurrence rate exceeded 65% in the 43-month median follow-up after laser ablation therapy. Jelmyto has shown long-term durability, surpassing the durability of kidney preservation programs such as laser ablation. However, the researchers said that the limitations of the study include the small sample size and the lack of data on the lasting response of 8 of the 23 patients 12 months after the PDE visit, which requires further trials to verify.
Jelmyto drug introduction
Product name: Jelmyto
Drug name: Mitomycin
Manufacturer: UroGen Pharma
Jelmyto is an alkylating agent. The active ingredient is mitomycin. It can inhibit the transcription of DNA into RNA, thereby preventing protein synthesis and depriving cancer cells of their ability to reproduce. Jelmyto uses a standard ureteral catheter to deliver to the patient's lesion, so that the urinary tract tissue can be exposed to the action of mitomycin for a long time, so as to achieve non-surgical elimination of tumors. The drug has been granted fast-track qualification, orphan drug qualification, priority review qualification and breakthrough therapy certification by the FDA. On April 16, 2020, the U.S. FDA announced the approval of mitomycin gel Jelmyto for the market for the treatment of low-grade urothelial carcinoma.
Reminder: Jelmyto is the first approved drug therapy for a specific patient group of low-grade urothelial carcinoma. It helps patients obtain more lasting therapeutic effects and provides these patients with an alternative to surgery. Treatment option.
