BALVERSA™ (erdafitinib) Receives U.S. FDA Approval for the Treatment of Patients with Locally Advanced or Metastatic Urothelial Carcinoma with Certain FGFR Genetic Alterations

-- BALVERSA is the first FGFR kinase inhibitor to receive U.S. FDA approval

-- Simultaneous approval of companion diagnostic intended to identify a subset of patients most likely to benefit from BALVERSA, offering a personalized treatment approach

HORSHAM, PA, USA I April 12, 2019 I The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that BALVERSA™ (erdafitinib) received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adults with locally advanced or metastatic urothelial carcinoma (mUC) which has susceptible fibroblast growth factor receptor (FGFR)3 or 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.1 BALVERSA is the first FGFR kinase inhibitor approved by the FDA. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1 Today's approval follows FDA Breakthrough Therapy Designation in March 2018 and Priority Review Designation of the New Drug Application submitted in September 2018.

"I've spent my career specializing in the care of patients with metastatic urothelial carcinoma and understand the need for new treatments for this disease," said Arlene O. Siefker-Radtke, M.D., professor of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, and lead study investigator. "BALVERSA is an important new therapy for this small subset of patients with urothelial carcinoma who, up until now, had limited treatment options." 

BALVERSA, a once-daily oral FGFR kinase inhibitor, received accelerated approval based on results from a Phase 2 clinical trial (BLC2001, NCT02365597), a multicenter, open-label, single-arm study, of 87 patients with disease that had progressed on or after at least one prior chemotherapy and that had at least one of the following genetic alterations: FGFR3 gene mutations (R248C, S249C, G370C, Y373C) or FGFR gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7), as determined by a clinical trial assay performed at a central laboratory.1 The results demonstrated a 32.2 percent objective response rate (ORR) as assessed by Blinded Independent Review Committee (BIRC) [95% CI(22.4, 42.0)].1 Responders included patients who had previously not responded to anti PD-L1/PD-1 therapy.1 In the trial, ORR was defined as the percentage of patients with measurable lesions achieving a complete response (CR) [2.3 percent] or partial response (PR) [29.9 percent]1 to treatment using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria, a standard way to measure how well a patient responds to treatment based on whether tumors shrink, stay the same, or get bigger as assessed per investigator.2 Results also showed a median duration of response (DoR) of 5.4 months [95% CI(4.2, 6.9)] in patients treated with BALVERSA.1There were no confirmed responses to BALVERSA in the FGFR2 fusion patient population (n=6).1 Data from the BLC2001 study were presented at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting (Abstract #4503) and were recognized as a "Best of ASCO" selection.

Warnings and Precautions include Ocular Disorders, Hyperphosphatemia and Embryo-fetal Toxicity.The most common adverse reactions (ARs) including laboratory abnormalities >20% were phosphate increased (76%), stomatitis (56%), fatigue (54%), creatinine increased (52%), diarrhea (47%), dry mouth (45%), onycholysis (41%), alanine aminotransferase increased (41%), alkaline phosphatase increased (41%), sodium decreased (40%), decreased appetite (38%), albumin decreased (37%), dysgeusia (37%), hemoglobin decreased (35%), dry skin (34%), aspartate aminotransferase increased (30%), magnesium decreased (30%), dry eye (28%), alopecia (26%), palmar-plantar erythrodysesthesia syndrome (26%), constipation (28%), phosphate decreased (24%), abdominal pain (23%), calcium increased (22%), nausea (21%), and musculoskeletal pain (20%). The most common Grade 3 or greater ARs (>1%) were stomatitis (9%), nail dystrophy*, palmar-plantar erythrodysesthesia syndrome (6%), paronychia (3%), nail disorder*, keratitis^, onycholysis (10%*) and hyperphosphatemia. (*Included within onycholysis. ^Included within dry eye.)

The FDA simultaneously approved a companion diagnostic for use with BALVERSA, the QIAGEN therascreen® FGFR RGQ Reverse-transcription (RT)-polymerase chain reaction (PCR) Kit, which is the first PCR-based companion diagnostic approved to detect FGFR alterations. The therascreen® FGFR test detects the presence of FGFR alterations in the tumor tissue of patients with mUC.1 If one or more of the genetic alterations or fusions are detected, the patient may be a candidate for treatment with BALVERSA. Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial carcinoma is available at: http://www.fda.gov/CompanionDiagnostics

Janssen is offering BALVERSA and associated patient services through a single source specialty pharmacy provider, US Bioservices. This model is part of Janssen's ongoing commitment to provide high-quality products, services, access, and support to healthcare professionals and patients. 

"We recognize the significant unmet need that persists in the treatment of men and women diagnosed with this form of urothelial carcinoma, and we have worked expeditiously to develop BALVERSA for patients in close consultation with the FDA," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "We look forward to the continued development of BALVERSA to understand how this important new therapy may further inform the care of patients with metastatic urothelial carcinoma and its investigational use in other cancers where FGFR alterations may be present in the future." 

"The FDA approval of BALVERSA represents our commitment to deliver much-needed therapies for devastating diseases, including metastatic urothelial carcinoma where there is a lack of therapeutic options," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "We are also pleased to see the simultaneous FDA approval of a companion diagnostic with BALVERSA, which will offer a more personalized approach to therapy for healthcare professionals to treat their patients." 

Full prescribing information will be available at www.BALVERSA.com.   

About Urothelial Carcinoma
Urothelial carcinoma, also known as transitional cell carcinoma, starts in the innermost lining of the bladder.3 It is the most common and frequent form of bladder cancer, representing more than 90 percent of all bladder cancers.4 About one in five patients with mUC have a FGFR genetic alteration.5,6 FGFRs are a family of receptor tyrosine kinases which can be activated by genetic alterations in a variety of tumor types, and these alterations may lead to increased tumor cell growth and survival.7 BALVERSA is approved specifically for the treatment of patients with mUC harboring FGFR3 or FGFR2 genetic alterations. In the U.S., it is estimated that up to 3,000 people with urothelial carcinoma will test FGFR positive on an annual basis.5,6,8,9 FGFR genetic alterations can be detected through an FDA-approved companion diagnostic. The five-year survival rate for patients with Stage IV metastatic bladder cancer that has spread to distant parts of the body is currently five percent.10

About BALVERSA™ (erdafitinib)
BALVERSA (erdafitinib) is a once-daily, oral fibroblast growth factor receptor (FGFR) kinase inhibitor indicated for the treatment of adults with locally advanced or metastatic urothelial carcinoma (mUC) which has susceptible FGFR3 or 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.1 This indication is approved under accelerated approval based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1 

The pivotal multicenter, open-label Phase 2 BLC2001 (NCT02365597) clinical trial evaluated the efficacy and safety of BALVERSA for the treatment of adults with mUC whose tumors have certain FGFR alterations. In 2008, Janssen entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialize BALVERSA. BALVERSA will be commercially available through the single-source specialty pharmacy provider US Bioservices.

For more information about BALVERSA, visit www.BALVERSA.com.

Indication

BALVERSA is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma which has

  • susceptible FGFR3 or FGFR2 genetic alterations and
  • progressed during or following at least one line of prior platinum-containing chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA.

This indication is approved under accelerated approval based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal and www.twitter.com/JanssenUS. Janssen Research & Development, LLC is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

1 BALVERSA Prescribing Information.
2 National Cancer Institute. NCI Dictionary of Cancer Terms. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/recist. Accessed April 2019.
3 American Cancer Society. "What is Bladder Cancer." Available at https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed April 2019.
4 National Cancer Institute. "Bladder Cancer Treatment (PDQ®)–Health Professional Version". Available at: https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq#link/_21_toc.  Accessed April 2019.
5 Helsten et al. The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing. Clin Cancer Res. 2015;22(1):259-267.
6 Tomlinson et al. FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol. 2007;213(1):91-98.
7 Dienstmann R, Rodon J, Prat A, et al. Genomic aberrations in the FGFR pathway: Opportunities for targeted therapies in solid tumors. Ann Oncol. 2014;25:552–563.
8 Janssen Pharmaceuticals, Inc. Data on file.
9 U.S. and World Population Clock. https://www.census.gov/popclock/. Accessed April 2019.
10 Bladder Cancer: Statistics. Available at: https://www.cancer.net/cancer-types/bladder-cancer/statistics. Accessed April 2019.

SOURCE: Janssen Pharmaceutical Companies

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