On May 6, 2024 FibroGen, Inc. (NASDAQ: FGEN) reported financial results for the first quarter 2024 and provided an update on the company’s recent developments (Press release, FibroGen, MAY 7, 2024, View Source [SID1234642657]).

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"We are off to a strong start in 2024 marked by the recent release of compelling Phase 1 data on FG-3246, our CD46 targeted antibody drug conjugate, in metastatic castration-resistant prostate cancer and continued robust growth of our roxadustat business in China," said Thane Wettig, Chief Executive Officer, FibroGen. "Looking ahead, we expect to report topline data from our two late-stage clinical trials of pamrevlumab in pancreatic cancer in the coming months. In addition, we have a strong balance sheet and reaffirm our cash runway into 2026."

Upcoming Milestones:

Pamrevlumab

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Topline data from the PanCAN Precision PromiseSM Phase 2/3 study of pamrevlumab in metastatic pancreatic cancer expected in mid-2024, reflecting PanCAN’s updated timing to complete database lock and subsequent analysis of the topline results by the independent Statistical Monitoring Committee.
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Topline data from the LAPIS Phase 3 study of pamrevlumab in locally advanced unresectable pancreatic cancer (LAPC) expected in 3Q 2024, due to the current trend in reported blinded overall survival events needed to complete the study.
Roxadustat

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Expect approval decision for roxadustat in chemotherapy-induced anemia (CIA) in China in the second half of 2024. If approved, FibroGen will receive a $10 million milestone payment from AstraZeneca.
Oncology Pipeline

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Initial data from Phase 1 investigator-initiated combination study of FG-3246 with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) to be presented at ASCO (Free ASCO Whitepaper) 2024.
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Anticipate initiation of Phase 2 monotherapy dose optimization study of FG-3246 in mCRPC in 2H 2024.
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Anticipate filing of an IND for FG-3175 (anti-CCR8 mAb) in 2025.

Recent Developments:

Oncology Pipeline

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Additional data from a total of 56 biomarker unselected and heavily pre-treated patients in a Phase 1 monotherapy study of FG-3246 in mCRPC reported.
o
Efficacy analysis (includes adenocarcinoma patients receiving doses ≥ 1.2 mg/kg):
▪
The median radiographic progression free survival (rPFS) in this patient population was 8.7 months.
▪
For RECIST evaluable patients, 20% met the criteria of a partial response, or measurable tumor reduction in size of ≥ 30%, with a median duration of response of 7.5 months.
▪
PSA reductions of ≥ 50% were observed in 36% of PSA evaluable patients
o
Safety analysis:
▪
The most frequent adverse events were consistent with other MMAE-based antibody drug conjugates and included infusion-related reactions, fatigue, weight loss, neutropenia, and peripheral neuropathy.
•
IND submitted for FG-3165 (Galectin-9 targeting mAb) for solid tumors in April 2024.
Corporate

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Appointed Deyaa Adib, MD as Chief Medical Officer.

China:

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First quarter FibroGen net product revenue under U.S. GAAP from the sale of roxadustat in China was $30.5 million compared to $24.2 million in the first quarter of 2023, an increase of 26% year over year.
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First quarter total roxadustat net sales in China1 by FibroGen and the distribution entity jointly owned by FibroGen and AstraZeneca (JDE) was $79.4 million, compared to $64.1 million in the first quarter of 2023, an increase of 24% year over year, driven by a 39% increase in volume.
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Roxadustat continues to be the number one brand based on value share in the anemia of CKD market in China.
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For 2024, we reiterate FibroGen’s full year net product revenue under U.S. GAAP to range between $120 million to $135 million, representing full year roxadustat net sales in China1 by FibroGen and the JDE to range between $300 million to $340 million.

Financial:

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Total revenue for the first quarter of 2024 was $55.9 million, as compared to $36.2 million for the first quarter of 2023, an increase of 55% year over year. Total revenue increase was driven by net product revenue in China and one-time drug product revenue of $25.7 million recognized due to the termination of US/RoW AstraZeneca agreement.
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Net loss for the first quarter of 2024 was $32.9 million, or $0.33 net loss per basic and diluted share, compared to a net loss of $76.7 million, or $0.81 net loss per basic and diluted share one year ago.
•
At March 31, 2024, FibroGen reported $214.7 million in cash – defined as cash, cash equivalents, investments, and accounts receivable.
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We expect our cash, cash equivalents, investments, and accounts receivable to be sufficient to fund our operating plans into 2026.

Conference Call and Webcast Details

FibroGen will host a conference call and webcast today, Monday, May 6, 2024, at 5:00 PM Eastern Time to discuss financial results and provide a business update. Interested parties may access a live audio webcast of the conference call via the "Investor Relations" page of the Company’s website at www.fibrogen.com.To access the call by phone, please go to this link (registration link), and you will be provided with dial in details. To avoid delays, we encourage participants to dial into the conference call fifteen minutes ahead of the scheduled start time. A replay of the webcast will also be available for a limited time at the following link (webcast replay).

About Pamrevlumab

Pamrevlumab is a potential first-in-class antibody being developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF). Pamrevlumab is in Phase 3 clinical development for the treatment of locally advanced unresectable pancreatic cancer (LAPC) and in Phase 2/3 for the treatment of metastatic pancreatic cancer. The U.S. Food and Drug Administration has granted Orphan Drug Designation, and Fast Track designation to pamrevlumab for the treatment of patients with LAPC. Pamrevlumab has demonstrated a safety and tolerability profile that has supported ongoing clinical investigation in LAPC and metastatic pancreatic cancer. Pamrevlumab is an investigational drug and not approved for marketing by any regulatory authority. For information about our pamrevlumab studies please visit www.clinicaltrials.gov.

About Roxadustat

Roxadustat, an oral medication, is the first in a new class of medicines comprising HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted by the China Health Authority.

Roxadustat is approved in China, Europe, Japan, and numerous other countries for the treatment of anemia of CKD in adult patients on dialysis (DD) and not on dialysis (NDD). Several other licensing applications for roxadustat have been submitted by partners, Astellas and AstraZeneca, to regulatory authorities across the globe, and are currently under review. Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia, and the Commonwealth of Independent States, the Middle East, and South Africa. AstraZeneca and FibroGen continue to collaborate on the development and commercialization of roxadustat in China.

On May 6, 2024 AstraZeneca reported the successful completion of an equity investment with Cellectis, a clinical-stage biotechnology company (Press release, AstraZeneca, MAY 6, 2024, View Source [SID1234642650]).

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The equity investment and a research collaboration agreement, announced in November 2023 will leverage the Cellectis proprietary gene editing technologies and manufacturing capabilities, to design up to 10 novel cell and gene therapy products for areas of high unmet need, including oncology, immunology and rare diseases.

Financial considerations
In Q4 2023, Cellectis received an initial payment of $105m from AstraZeneca, which comprised a $25m upfront cash payment under the terms of a research collaboration agreement and an $80m equity investment.

An additional $140m equity investment, at $5/share, has closed following the satisfaction of customary closing conditions including Cellectis shareholders’ approval and regulatory clearances. Post-closing of this second investment, AstraZeneca holds a total equity stake of c.44% in Cellectis. AstraZeneca expects to continue to treat its investment in Cellectis as an associate.

Under the terms of the research collaboration, Cellectis is also eligible to receive an investigational new drug (IND) option fee and development, regulatory and sales-related milestone payments, ranging from $70m up to $220m, per each of the 10 candidate products, plus tiered royalties.

AstraZeneca retains an option for a worldwide exclusive license for the candidate products developed under the research collaboration agreement, to be exercised before IND filing.

On May 5, 2024 Johnson & Johnson reported updated results from an open-label, multicenter, multi-cohort Phase 1 study of the safety and efficacy of TAR-210, an intravesical targeted releasing system designed to provide sustained, local release of erdafitinib into the bladder, in patients with non–muscle-invasive bladder cancer (NMIBC) with select FGFR alterations (Press release, Johnson & Johnson, MAY 5, 2024, View Source [SID1234642649]). These data were featured today in an Oral Presentation Session (Abstract # PD48-02) at the 2024 American Urological Association (AUA) Annual Meeting taking place May 3-6, 2024, in San Antonio, Texas.

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Results featured updated data from Cohort 1 (C1), patients with recurrent, Bacillus Calmette-Guérin (BCG)–unresponsive high-risk (HR) NMIBC (high-grade Ta/T1; papillary only) who refused or were ineligible for radical cystectomy and Cohort 3 (C3), patients with recurrent, intermediate-risk NMIBC (Ta/T1) low-grade papillary disease left in situ as tumor marker lesions. First results were featured at the European Society for Medical Oncology 2023 Congress, with interim results presented at the European Association of Urology (EAU) 2024 Annual Congress.

"Advancement in the treatment landscape of high- or intermediate-risk non–muscle-invasive bladder cancer has remained stagnant for more than 50 years," said Antoni Vilaseca,* M.D., Ph.D., of the Hospital Clínic de Barcelona, presenting author of the Phase 1 TAR-210 study. "Results presented today further underscore that TAR-210 for the localized treatment of bladder cancer may offer a promising alternative for patients with limited treatment options."

At the data cutoff of March 22, 2024, 64 patients had been treated with TAR-210 across the 2 cohorts. Of the 21 patients in C1 with HR-NMIBC, the 12-month recurrence-free (RF) survival rate was 90%. In C3, 31 patients were efficacy evaluable with a complete response (CR) rate of 90%.1

The most common treatment emergent adverse events (TEAEs) were Grade 1/2 lower urinary tract events. There were no dose-limiting toxicities and no deaths. Two patients (3%) discontinued the study due to TEAEs of low-grade urinary symptoms and two patients had serious TEAEs with pyelonephritis and sepsis or UTI and sepsis, respectively.1

"FGFR genetic alterations are most common in NMIBC," said Sabine Brookman-May, M.D., Vice President, Late Development Oncology, Johnson & Johnson Innovative Medicine. "These results further support the potential of TAR-210 with quarterly administration as a bladder-sparing and BCG-free treatment option, underscoring our deep commitment to pioneering novel therapies for patients who face limited treatment avenues."

TAR-210 is an investigational targeted releasing system designed to provide sustained local release of erdafitinib. Oral erdafitinib was approved by the U.S. Food and Drug Administration (FDA) as BALVERSA (erdafitinib) for patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible FGFR3 genetic alterations that have progressed on or after at least one line of prior systemic therapy. BALVERSA is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy.2

Bladder cancer ranks as the sixth most prevalent cancer in the U.S., with over 83,000 individuals receiving diagnoses annually.3 NMIBC constitutes approximately 75-85% of these cases.4 Currently, adjuvant intravesical immunotherapy with BCG or intravesical chemotherapy is the standard of care for patients with intermediate- and high-risk NMIBC.5 Between 30 and 40% of patients do not respond to BCG, facing disease recurrence or progression.6 In such scenarios of HR-NMIBC, radical cystectomy (removal of the bladder) emerges as the primary treatment option. This major abdominal procedure requires a urinary diversion to be created to collect and store urine.7

About TAR-210
TAR-210 is an investigational erdafitinib intravesical targeted releasing system. The safety and efficacy of TAR-210 is being evaluated in a Phase 1 study (NCT05316155) in patients with muscle-invasive bladder cancer (MIBC) and NMIBC. The study categorizes patients into 4 cohorts based on their disease presentation. Cohort 1 includes patients with recurrent, BCG-unresponsive high-risk NMIBC with concomitant high-grade papillary disease who have refused or are ineligible for radical cystectomy (RC). Cohort 2 includes patients with the same presentation, but who are scheduled for RC. Cohort 3 includes patients with recurrent, intermediate-risk NMIBC with a history of low-grade papillary disease. To be eligible for C3, the presence of visible tumor(s) is required. Cohort 4 includes patients with MIBC. The primary endpoint of the study is safety (adverse events, including dose-limiting toxicity). Secondary endpoints include pharmacokinetics, RF survival in patients in C1 and C2, CR rate and duration of CR in patients in C3 and pathologic CR rate in C4.8

About BALVERSA
BALVERSA (erdafitinib) is a once-daily, oral FGFR kinase inhibitor indicated for the treatment of adult patients with locally advanced or mUC with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. BALVERSA is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-(L)1 inhibitor therapy.2 Patients are selected for therapy based on an FDA-approved companion diagnostic for BALVERSA. Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer is available at: View Source

BALVERSA received Breakthrough Therapy Designation from the U.S. FDA in 2018 and received accelerated approval in 2019 for the treatment of adults with locally advanced or mUC that has susceptible FGFR3 or fibroblast growth factor receptor 2 (FGFR2) genetic alterations and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.2

The Company submitted a marketing authorization application to the European Medicines Agency in September 2023 for BALVERSA as a treatment for adult patients with FGFR3-altered, locally advanced unresectable or mUC that has progressed following therapy with a PD-(L)1 inhibitor.

In 2008, Janssen Pharmaceuticals entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialize BALVERSA.

For more information, visit www.BALVERSA.com.

BALVERSA IMPORTANT SAFETY INFORMATION

WARNING AND PRECAUTIONS

The safety population described in the Warnings and Precautions reflect a pooled safety population of 479 patients with advanced urothelial cancer and FGFR alterations who received BALVERSA.

Ocular Disorders – BALVERSA can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) resulting in visual field defect.

CSR/RPED occurred in 22% of patients treated with BALVERSA, with a median time to first onset of 46 days. In 104 patients with CSR, 40% required dose interruptions and 56% required dose reductions; 2.9% of BALVERSA-treated patients required permanent discontinuation for CSR. Of the 24 patients who restarted BALVERSA after dose interruption with or without dose reduction, 67% had recurrence and/or worsening of CSR after restarting. CSR was ongoing in 41% of the 104 patients at the time of last evaluation.

Dry eye symptoms occurred in 26% of BALVERSA-treated patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed.

Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms. Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography. Withhold or permanently discontinue BALVERSA based on severity and/or ophthalmology exam findings.

Hyperphosphatemia and Soft Tissue Mineralization – BALVERSA can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification. Increases in phosphate levels are a pharmacodynamic effect of BALVERSA [see Pharmacodynamics (12.2)]. Increased phosphate occurred in 73% of BALVERSA-treated patients. The median onset time of increased phosphate was 16 days (range: 8–421) after initiating BALVERSA. Twenty-four percent of patients received phosphate binders during treatment with BALVERSA. Vascular calcification was observed in 0.2% of patients treated with BALVERSA.

Monitor for hyperphosphatemia throughout treatment. In all patients, restrict phosphate intake to 600-800 mg daily and avoid concomitant use of agents that may increase serum phosphate levels. If serum phosphate is above 7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate level returns to <7.0 mg/dL. Withhold, dose reduce, or permanently discontinue BALVERSA based on duration and severity of hyperphosphatemia.

Embryo-Fetal Toxicity – Based on the mechanism of action and findings in animal reproduction studies, BALVERSA can cause fetal harm when administered to a pregnant female. In a rat embryo-fetal toxicity study, erdafitinib caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum human recommended dose based on AUC. Advise pregnant patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA and for one month after the last dose.

Adverse Reactions
In this pooled safety population described in Warnings and Precautions, the median duration of treatment was 4.8 months (range: 0.1 to 43 months). The most common (>20%) adverse reactions, including laboratory abnormalities, were increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy.

In Cohort 1 of the BLC3001 (NCT03390504, THOR) study:

Serious adverse reactions occurred in 41% of patients who received BALVERSA. Serious reactions in >2% of patients included urinary tract infection (4.4%), hematuria (3.7%), hyponatremia (2.2%), and acute kidney injury (2.2%). Fatal adverse reactions occurred in 4.4% of patients who received BALVERSA, including sudden death (1.5%), pneumonia (1.5%), renal failure (0.7%), and cardiorespiratory arrest (0.7%).
Permanent discontinuation of BALVERSA due to an adverse reaction occurred in 14% of patients. Adverse reactions which resulted in permanent discontinuation of BALVERSA in >2% of patients included nail disorders (3%) and eye disorders (2.2%).
Dosage interruptions of BALVERSA due to an adverse reaction occurred in 72% of patients. Adverse reactions which required dosage interruption in >4% of patients included nail disorders (22%), stomatitis (19%), eye disorders (16%), palmar-plantar erythrodysesthesia syndrome (15%), diarrhea (10%), hyperphosphatemia (7%), increased aspartate aminotransferase (6%), and increased alanine aminotransferase (5%).
Dose reductions of BALVERSA due to an adverse reaction occurred in 69% of patients. Adverse reactions which required dose reductions in >4% of patients included nail disorders (27%), stomatitis (19%), eye disorders (17%), palmar-plantar erythrodysesthesia syndrome (12%), diarrhea (7%), dry mouth (4.4%), and hyperphosphatemia (4.4%).
Clinically relevant adverse reactions in <15% of patients who received BALVERSA included nausea (15%), pyrexia (15%), epistaxis (13%), vomiting (10%), and arthralgia (10%).
Drug Interactions

Effects of Other Drugs on BALVERSA

Moderate CYP2C9 or Strong CYP3A4 Inhibitors: Consider alternative agents; however, if co-administration is unavoidable, monitor closely for adverse reactions.
Strong CYP3A4 inducers: Avoid co-administration with BALVERSA.
Moderate CYP3A4 inducers: If co-administration is required at the start of BALVERSA treatment, administer BALVERSA at a dose of 9 mg daily.
Serum phosphate level-altering agents: Avoid co-administration with agents that can alter serum phosphate levels before the initial dose increase period based on serum phosphate levels.
Effect of BALVERSA on Other Drugs

P-gp substrates: If co-administration is unavoidable, separate BALVERSA administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic indices.
Please click here to see full BALVERSA Prescribing Information.

About High-Risk Non–Muscle-Invasive Bladder Cancer
High-risk non-muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer compared to low-risk NMIBC. HR-NMIBC makes up 15-44% of patients with NMIBC and is characterized by a combination of high-grade, large tumor size, presence of multiple tumors, and carcinoma in situ. Radical cystectomy (RC) is currently recommended for NMIBC patients who fail BCG therapy, with over 90% cancer-specific survival if performed before muscle-invasive progression. Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo RC. The high rates of recurrence and progression can pose significant morbidity and distress for these patients.

On May 4, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported results from a new analysis of the ATLAS trial, which estimates using Kaplan Meier methods the probabilities of remaining in complete response for both new and recurrent low-grade intermediate-risk non- muscle invasive bladder cancer (LG-IR-NMIBC) patients following treatment with investigational drug UGN-102 as primary therapy, with or without subsequent transurethral resection of the bladder tumor (TURBT) at 3 months (Press release, UroGen Pharma, MAY 4, 2024, View Source [SID1234642645]).

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"These compelling findings shed light on the potential of UGN-102 as a nonsurgical primary treatment for low-grade intermediate-risk bladder cancer," said William Huang, M.D., Urologic Oncologist, Professor and Vice Chair of Urology, NYU Grossman School of Medicine. "These data are an encouraging step forward in addressing the broad spectrum of LG-IR-NMIBC and potentially curbing the high rates of disease recurrence associated with it."

In the Phase 3 ATLAS study, 282 patients with new or recurrent LG-IR-NMIBC were randomized to primary treatment with UGN-102 ± TURBT or TURBT alone. In the overall study population, Disease Free Survival (DFS) and DOR favored primary treatment with UGN-102 ± TURBT compared to TURBT alone. Complete response (CR) rates at the 3-month disease assessment were similar in both arms. While DFS and DOR rates were previously shared for both arms of the study, these are the first data specifically looking at the rates among new and recurrent patients within the UGN-102 ± TURBT arm. In this analysis using Kaplan Meier methods, DOR at 12 months after achieving CR at 3 months was 87.5% and 69.1% in new and recurrent patients, respectively. Also, patients achieved similar probabilities of DFS rates for UGN-102 at 15 months from randomization (77.4% and 63.2% in new and recurrent patients, respectively).

"These insightful data underscore the potential of UGN-102 impacting the treatment landscape for LG-IR-NMIBC," said Mark Schoenberg, M.D., Chief Medical Officer, UroGen. "Our aim is for UGN-102 to emerge as a non-surgical option for LG-IR-NMIBC, potentially sparing patients from the complexities and burdens associated with repetitive surgeries, including their inherent risks, side effects, and substantial impact on both individuals and healthcare systems."

Topline data from both the ATLAS trial and the Phase 3 ENVISION trial were initially shared in July of 2023. Twelve-month DOR data from the pivotal Phase 3 ENVISION trial are expected in June 2024.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting. Assuming positive findings from the durability of response endpoint from the ENVISION Phase 3 study, UroGen anticipates completing its New Drug Application (NDA) submission for UGN-102 in September 2024 with a potential U.S. Food and Drug Administration (FDA) decision as early as the first quarter of 2025.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

In the U.S. bladder cancer is the second most common urologic cancer in men. LG-IR- NMIBC represents approximately 22,000 newly diagnosed bladder cancer patients each year and an estimated 60,000 recurrences annually among patients diagnosed from previous years. Bladder cancer primarily affects older populations with the median age of diagnosis 73 years and an increased risk of comorbidities. Guideline recommendations for the management of NMIBC include TURBT as the standard of care (SOC). Up to 70 percent of NMIBC patients experience at least one recurrence and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures.

About ATLAS

ATLAS was a global, open-label, randomized controlled Phase 3 trial designed to assess the efficacy and safety of UGN-102, with or without TURBT, vs. TURBT alone in patients diagnosed with LG-IR-NMIBC. The trial enrolled 282 patients in clinical sites in the U.S., Europe and Israel. Patients were randomized 1:1 to either UGN-102 or TURBT. Patients in the UGN-102 arm were treated with six weekly intravesical instillations of UGN-102. At the 3-month time point, patients were assessed for response. Patients who demonstrated a complete response to either UGN-102 or TURBT, were assessed for long-term duration of response. Patients who demonstrated presence of persistent disease at 3-months, in either arm, underwent a TURBT and continued for long-term follow-up for evidence of recurrence. The primary endpoint of the study is disease-free survival. Learn more about the ATLAS trial at www.clinicaltrials.gov (NCT04688931).

About ENVISION

The Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 (mitomycin) for intravesical solution as primary chemoablative therapy in patients with LG-IR-NMIBC. The Phase 3 ENVISION trial completed target enrollment with approximately 240 patients across 56 sites. Study participants received six once-weekly intravesical instillations of UGN-102. The primary endpoint evaluated the CR rate at the 3-month assessment after the first instillation, and the key secondary endpoint will evaluate durability over time in patients who achieved a CR at the 3-month assessment. Based on discussions with the FDA, and assuming positive findings, UroGen anticipates submitting an NDA for UGN-102 in September 2024. Learn more about the Phase 3 ENVISION trial at www.clinicaltrials.gov (NCT05243550).

On May 4, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported the results of a sub-analysis from a real-world patient cohort review of JELMYTO (mitomycin) for pyelocalyceal solution presented at the American Urological Association Meeting 2024 in San Antonio, TX (Press release, UroGen Pharma, MAY 4, 2024, View Source [SID1234642644]). The study includes a stepwise approach to retrograde administration of JELMYTO and reports that retrograde administration of JELMYTO in the clinic (n=20) produced a 60% complete response rate in patients and ureteral stents were placed in 25% of patients, which is lower than the rate reported in the pivotal OLYMPUS study.

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"The retrograde instillation of JELMYTO for the clinical management of low-grade upper tract urothelial cancer is FDA-approved and offers a safe and efficacious mode of administration, and this study in a real-world population adds to the growing body of evidence supporting retrograde administration in appropriate patients," said Khurshid Ridwan Ghani, MBChB, MS, FRCS, Professor of Urology, Director, Michigan Urological Surgery Improvement Collaborative. "The stepwise approach outlined in this study offers valuable insights into achieving positive efficacy and safety outcomes, in the clinic with the procedure done under local anesthesia, with notable durability of response observed."

In the OLYMPUS study all enrolled patients (n=71) received retrograde administration of JELMYTO. In the OLYMPUS study 58% (n=41) of patients achieved a complete response, defined as the absence of tumor lesions 3 months after initiation of JELMYTO treatment assessed by urine cytology and ureteroscopy. Ureteric obstruction* was reported in 58% (n=41) of patients treated with JELMYTO and 88% (n=36) of that subgroup went on to receive ureteral stent placement. For additional information about the retrograde administration of JELMYTO, consult the JELMYTO Instructions for Administration accompanying the Full Prescribing Information.

In this retrospective real-world study, 20 patients with a mean tumor burden of 1.67 cm received at least one dose of JELMYTO via the retrograde mode of administration, of which 16 (80%) completed six instillations. Twelve patients (60%) had a complete response and seven patients (35%) received at least one dose of monthly maintenance therapy, of which five demonstrated durability of response (4 patients remained tumor-free at 14.25-month follow-up and 1 patient at 24 months). Six patients (30%) had an adverse event related to the urinary system. Ureteral stents were placed in five patients for stenosis (25%); of which four were transient, with no subsequent obstruction. Only one patient (5%) required permanent stenting. Three patients who were unable to tolerate the retrograde approach had antegrade administration of JELMYTO via a nephrostomy tube.

"These findings emphasize the versatility of JELMYTO administration and also underscore the significance of continuous research and innovation in elevating treatment standards for urothelial cancers," remarked Mark Schoenberg, M.D., Chief Medical Officer at UroGen.

The limitations of this sub-analysis include the small sample size, the retrospective design, lack of a control group, and the lack of a centralized pathology review and standardized clinicopathologic assessment.

To further explore the full potential of JELMYTO for the treatment of patients with upper tract urothelial cancers (UTUC), investigators are in the process of enrolling the prospective and retrospective uTRACT Registry to capture data in a large-scale, standardized manner to report further on patient outcomes following JELMYTO treatment including longitudinal follow-up.

*Includes hydronephrosis, obstructive uropathy, pelvic-ureteric obstruction, ureteric obstruction, ureteric stenosis, and urinary tract obstruction.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for the treatment of adult patients with low grade-UTUC (LG-UTUC). JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

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 UTUC. In the U.S., there are approximately 6,000 – 7,000 new or recurrent LG-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.