On May 6, 2024 ADC Therapeutics SA (NYSE: ADCT) reported financial results for the first quarter ended March 31, 2024, and provided business updates (Press release, ADC Therapeutics, MAY 6, 2024, View Source [SID1234642661]).

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"During the first quarter of 2024, we were pleased to see continued progress from our corporate and capital allocation strategy focused primarily on hematology with ZYNLONTA while advancing our emerging solid tumor pipeline," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "In hematology, we delivered sequential ZYNLONTA revenue growth. We were pleased to announce that our LOTIS-7 study of ZYNLONTA in combination with bispecifics has successfully cleared the final dosing cohort and enrollment in Part 2 dose expansion has been initiated. Additionally, we were encouraged by the initial IIT Phase 2 data with ZYNLONTA in MZL which supports potential expansion in MZL and contributes to the overall ZYNLONTA growth strategy in NHL. With multiple potential value-generating catalysts ahead this year including expected completion of enrollment in LOTIS-5, expansion of LOTIS-7 and initial read of ADCT-601 in AXL, I am excited about our prospects for continued progress in 2024."

Recent Highlights and Developments

ZYNLONTA (loncastuximab tesirine-lpyl)
•ZYNLONTA generated product net sales of $17.8 million in the first quarter of 2024, representing a 7% increase over the fourth quarter of 2023 and a 6% decrease over the first quarter of 2023. Sequential quarter-over-quarter growth in the first quarter of 2024 continued, with sales volume increasing in both community and academic settings. The year-over-year net sales decline reflected higher gross-to-net deductions and lower volume, partially offset by a higher price.
Hematology Pipeline
•LOTIS-5: The Phase 3 confirmatory trial for ZYNLONTA in combination with rituximab in patients with 2L+ diffuse large B-cell lymphoma (DLBCL) continues to see accelerated enrollment. The Company expects to complete enrollment of this trial in 2024.
•LOTIS-7: On April 4, 2024, The Company announced the completion of dose escalation in LOTIS-7, a Phase 1b open-label clinical trial evaluating ZYNLONTA in combination with bispecific antibodies glofitamab or mosunetuzumab in heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). In the dose escalation portion (Part 1) of LOTIS-7, no dose-limiting toxicities (DLTs), no or low-grade cytokine release syndrome (CRS) and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed across all patients when ZYNLONTA was administered in combination with glofitamab or mosunetuzumab. Additionally, after the first investigator assessment, evidence of anti-tumor activity (complete response or partial response) was observed among the majority of patients, with mixed histologies including r/r DLBCL, follicular lymphoma (FL) and marginal zone lymphoma (MZL). In addition, as of April 19, 2024, initial safety findings showed that the majority of CRS events seen were grade 1 (6 out of 18 patients) or grade 2 (2 of 18 patients, 11%), with no CRS greater than grade 2 observed in either combination arm. Furthermore, all grade 2 events responded to Tocilizumab/corticosteroids with no requirement for pressors or ICU management. Based on the data from Part 1, all three dose levels (90, 120 and 150 µg/kg) have now been cleared and enrollment in Part 2 dose expansion has been initiated with ZYNLONTA administered in combination with glofitamab at the 120 µg/kg and 150 µg/kg dose levels in 2L+ DLBCL patients.
•Investigator-Initiated Trial: As announced by the Company today, May 6, 2024, initial data from an investigator-initiated Phase 2 clinical trial evaluating ZYNLONTA for the treatment of relapsed/refractory (r/r) MZL were presented at the Lymphoma Research Foundation’s 2024 Marginal Zone Lymphoma Scientific Workshop by the trial’s lead investigator. The 50-patient single-arm, open-label Phase 2 multicenter study is currently being conducted at the Sylvester Comprehensive Cancer Center at University of Miami and City of Hope, and led by Izidore Lossos, MD, Professor, Director, Lymphoma Program at the Sylvester Comprehensive Cancer Center, University of Miami. This study is evaluating the safety and efficacy of ZYNLONTA in patients with r/r MZL previously treated with ≥1 line of systemic therapy (ClincalTrials.gov identifier: NCT05296070). As of the data cutoff date of March 30, 2024, 15 patients were evaluable. Of these 15 patients evaluated, 13 achieved a complete response (CR) and one patient achieved a partial response (PR). In this study, ZYNLONTA was generally well tolerated and the safety profile was consistent with the known profile, with two patient discontinuations. All patients who achieved responses had maintained them at the time of the data cutoff with the longest responder reaching approximately 20 months.

Solid Tumor Pipeline
•ADCT-601 (targeting AXL): The Phase 1b trial studying ADCT-601 targeting AXL continues enrolling patients in the pancreatic cancer monotherapy arm, optimizing dose and schedule. The ongoing dose-optimization/expansion phase is comprised of a monotherapy arm including patients with sarcoma, pancreatic cancer and AXL-expressing non-small cell lung cancer (NSCLC) and a combination arm with gemcitabine in patients with sarcoma and pancreatic cancer.
•Early-stage pipeline: On April 9, 2024, the Company hosted a virtual Research Investor Event during which details were shared on strategy and recent business updates as well as the Company’s novel exatecan-based ADC platform. The Company provided details on its four lead candidates – targeting Claudin-6, NaPi2b, PSMA and ASCT2 – which have a differentiated profile based on a novel, proprietary linker approach to tracelessly release exatecan and a high therapeutic index. The Company’s NaPi2b and Claudin-6 targeting ADCs are in IND-enabling studies and PSMA and ASCT2 targeting ADCs are in drug candidate selection stage, expected to complete this year. Preclinical data on the Claudin-6 and NaPi2b programs were shared in presentations at the AACR (Free AACR Whitepaper) Annual Meeting 2024 which demonstrated that each was well tolerated with potent and specific in vitro and in vivo anti-tumor activity.

Upcoming Expected Milestones

ZYNLONTA
•Achieve commercial brand profitability in 2024
•LOTIS-5: Complete enrollment in 2H 2024
•LOTIS-7: Part 2 enrollment complete with initial efficacy/safety update in 2H 2024; full/mature data in 1H 2025
•Investigator-initiated trial in r/r FL: The study is being expanded to 100 patients in a multicenter clinical trial. Updates are anticipated at medical meetings in 2024/2025.
•Investigator-initiated trial in r/r MZL: The study is designed to enroll 50 patients in a multicenter clinical trial. Further updates are anticipated at medical meetings in 2024/2025.

Pipeline

ADCT-601 (targeting AXL)
•Additional data updates from the Phase 1 study in patients with sarcoma, pancreatic cancer and NSCLC in 2H 2024

ADCT-602 (targeting CD22)
•Additional data from the Phase 1 study in 2H 2024

Preclinical
Advancing a broad portfolio of investigational ADCs for solid tumor indications

First Quarter 2024 Financial Results

Cash and Cash Equivalents

Cash and cash equivalents were $234.3 million as of March 31, 2024, compared to $278.6 million as of December 31, 2023. The Company currently expects its cash runway to extend into the fourth quarter of 2025.

Product Revenues

Net product revenues were $17.8 million for the first quarter 2024, compared to $19.0 million for the first quarter 2023. Net product revenues are for U.S. sales of ZYNLONTA. The decrease was primarily due to higher gross-to-net deductions and lower volume, partially offset by a higher price.

Research and Development (R&D) Expenses

R&D expenses were $25.7 million for the first quarter 2024, compared to $38.4 million for the first quarter 2023. R&D expenses decreased due to less investment in camidanlumab tesirine (Cami), as well as productivity initiatives and focused investment toward prioritized development programs. The decrease in R&D expenses related to Cami was primarily due to our evaluation of FDA feedback and decision to stop the program.

R&D expenses for the first quarter 2024 also decreased due to lower share-based compensation expense resulting from fluctuations in the share price and award forfeitures in connection with terminations.

Selling and Marketing (S&M) Expenses

S&M expenses were $11.4 million for the first quarter 2024, compared to $15.4 million for the first quarter 2023. The decrease in S&M expenses was primarily due to lower spend on marketing and advertising, lower wages and benefits, as well as lower share-based compensation expense resulting from fluctuations in the share price and award forfeitures in connection with terminations.

General & Administrative (G&A) Expenses

G&A expenses were $12.0 million for the first quarter 2024, compared to $15.5 million for the first quarter 2023. The decrease in G&A expenses was primarily due to lower share-based compensation expense resulting from fluctuations in the share price and award forfeitures in connection with terminations, lower wages and benefits and insurance costs, partially offset by higher professional fees including audit and legal fees.

Net Loss and Adjusted Net Loss

Net loss was $46.6 million, or a net loss of $0.56 per basic and diluted share, for the first quarter of 2024 and a net loss of $59.4 million, or a net loss of $0.73 per basic and diluted share for the first quarter of 2023. The decrease in net loss is primarily due to lower operating expenses, partially offset by changes in the fair value of our Deerfield warrant obligation and higher accretion of our deferred royalty obligation.

Adjusted net loss, which is a non-GAAP financial measure, was $31.1 million, or an adjusted net loss of $0.38 per basic and diluted share for the first quarter 2024 and $41.8 million, or an adjusted net loss of $0.52 per basic and diluted share for the first quarter 2023. The decrease in adjusted net loss for the quarter primarily reflects our lower operating expenses.

Conference Call Details

ADC Therapeutics management will host a conference call and live audio webcast to discuss first quarter 2024 financial results and provide a company update today at 8:30 a.m. Eastern Time. To access the conference call, please register here. Registrants will receive the dial-in number and unique PIN. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under "Events & Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at www.ZYNLONTA.com.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

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

•
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.
•
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

•
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

•
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.
•
Anticipate initiation of Phase 2 monotherapy dose optimization study of FG-3246 in mCRPC in 2H 2024.
•
Anticipate filing of an IND for FG-3175 (anti-CCR8 mAb) in 2025.

Recent Developments:

Oncology Pipeline

•
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

•
Appointed Deyaa Adib, MD as Chief Medical Officer.

China:

•
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.
•
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.
•
Roxadustat continues to be the number one brand based on value share in the anemia of CKD market in China.
•
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:

•
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.
•
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.
•
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).