On April 30, 2020 UroGen Pharma Ltd. (Nasdaq: URGN) reported The Lancet Oncology published results from the pivotal Phase 3 OLYMPUS trial, reporting that 59% of low-grade upper tract urothelial cancer (LG-UTUC) patients treated with UGN-101, now referred to as Jelmyto (mitomycin) for pyelocalyceal solution, achieved a Complete Response (CR) (Press release, UroGen Pharma, APR 30, 2020, View Source [SID1234556855]). Additionally, in the publication, durability at 12 months (based on interim data) was estimated to be 84% by Kaplan-Meier analysis.1

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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. Jelmyto is indicated for the treatment of adult patients with low-grade upper tract urothelial cancer (LG-UTUC). It is contraindicated in patients with perforation of the bladder or upper urinary tract.

"The current approach to treating low-grade upper tract urothelial cancer includes multiple endoscopic surgeries, high risk of disease recurrence and for many patients, the eventual removal of a kidney, which can present a whole new set of challenges that can adversely impact long-term health," said Seth Lerner, M.D., FACS, Professor of Urology at Baylor College of Medicine in Houston, TX and Principal Investigator of the OLYMPUS trial. "Data from the OLYMPUS trial suggest UGN-101 is associated with a higher than expected initial complete response rate and strong durability without additional endoscopic surgery, which represents significant progress for patients living with this rare and difficult-to-treat type of 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.2 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 function and may suffer further complications as a result of major surgery.

In the pivotal OLYMPUS trial, participants received six once-weekly instillations of Jelmyto via retrograde catheter in the renal pelvis and calyces. The intent-to-treat (ITT) population included the seventy-one patients who received at least one dose of Jelmyto; 48% of these patients had tumors that were deemed endoscopically unresectable. As reported in The Lancet Oncology publication, Jelmyto achieved a Complete Response (CR) in 59% of the ITT population (a CR was defined as negative 3-month ureteroscopic evaluation, negative cytology and negative for cause biopsy) and durability at 12 months (at the time of the data cutoff) was estimated to be 84% by Kaplan-Meier analysis.

"The positive results of the OLYMPUS trial demonstrate that Jelmyto has the potential to help fulfill a significant unmet need for patients with low-grade upper tract urothelial cancer," said Dr. Mark P. Schoenberg, Chief Medical Officer at UroGen. "We are committed to addressing treatment challenges for this underserved patient population and to improving the standard of care for those who need it most."

As reported in The Lancet Oncology publication, in the trial, 67 patients (94%) experienced adverse events (AEs) and 60 patients (85%) had AEs that were considered to be related to the study treatment or procedure. No treatment-related deaths occurred. Overall, the most frequently reported AEs were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%).

The U.S. Food and Drug Administration (FDA) approved Jelmyto on April 15, 2020. The FDA-approved labeling for Jelmyto reports Complete Response (CR) (primary endpoint) of 58% in the intent-to-treat population. The product labeling also reports that at the 12-month time point for assessment of durability, 19 patients remained in CR, seven had experienced recurrence of disease, nine patients continued to be followed for the 12-month duration of response, and median duration of response was not reached as of the FDA-approval date.

About the Phase 3 OLYMPUS Trial

OLYMPUS (Optimized DeLivery of Mitomycin for Primary UTUC Study) is an open-label, single-arm Phase 3 clinical trial of UGN-101, Jelmyto (mitomycin) for pyelocalyceal solution, to evaluate the safety, tolerability and tumor ablative effect of Jelmyto in patients with low-grade UTUC. Seventy-one patients were treated at clinical sites across the United States and Israel. Study participants were treated with six weekly instillations of Jelmyto administered via a standard catheter. Four to six weeks following the last instillation, patients underwent a Primary Disease Evaluation (PDE) to determine Complete Response (CR), the primary endpoint of the study. PDE involved a ureteroscopy and wash cytology, a standard microscopic test of cells obtained from the urine to detect cancer and for cause biopsy. Patients who achieved a CR at the PDE timepoint were then followed for up to 12 months to determine the durability of response with Jelmyto.

About Jelmyto

Jelmyto (mitomycin) for pyelocalyceal solution, is a drug formulation of mitomycin indicated for the treatment of adult patients with low-grade upper tract urothelial cancer (LG-UTUC). Utilizing the RTGel technology platform, UroGen’s proprietary sustained release, hydrogel-based formulation, Jelmyto is designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. Jelmyto is delivered to patients using standard ureteral catheters or nephrostomy tube. The U.S. FDA previously granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to Jelmyto for the treatment of LG-UTUC. On April 15, 2020, the FDA approved Jelmyto, making it the first drug approved for the treatment of LG-UTUC in adult patients.

About Upper Tract Urothelial Cancer (UTUC)

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as upper tract urothelial cancers (UTUC). In the U.S., there are approximately 6,000 – 7,000 new or recurrent low-grade UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). These treatments can lead to a high rate of recurrence and relapse.

IMPORTANT SAFETY INFORMATION

You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract.

Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:

are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO.
Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose.
Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose.
are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose.
Tell your healthcare provider if you take water pills (diuretic).
How will I receive JELMYTO?

Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.
You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses.
JELMYTO is given to your kidney through a tube called a catheter.
During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines.
After receiving JELMYTO:

JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours.
To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.
Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.
JELMYTO may cause serious side effects, including:

Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.
Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.
The most common side effects of JELMYTO include: side pain, urinary tract infection, blood in your urine, kidney problems, tiredness, nausea, stomach pain, trouble with urination, vomiting, low red blood cell count, frequent urination, itching, chills, and fever.