Safety

The safety profile of BALVERSA® was evaluated in a multicenter, open-label, single-arm phase 2 study1

The safety of BALVERSA® was evaluated in the BLC2001 study that included 87 patients with locally advanced or metastatic urothelial carcinoma which had susceptible FGFR3 or FGFR2 genetic alterations, and which progressed during or following at least one line of prior chemotherapy including within 12 months of neoadjuvant or adjuvant chemotherapy [see Clinical Studies (14.1) of the full Prescribing Information]. Patients were treated with BALVERSA® at 8 mg orally once daily, with a dose increase to 9 mg in patients with phosphate levels <5.5 mg/dL on Day 14 of Cycle 1. Median duration of treatment was 5.3 months (range: 0 to 17 months).

Ocular disorders1

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

CSR/RPED was reported in 25% of patients treated with BALVERSA®, with a median time to first onset of 50 days. Grade 3 CSR/RPED, involving central field of vision, was reported in 3% of patients. CSR/RPED resolved in 13% of patients and was ongoing in 13% of patients at the study cutoff. CSR/RPED led to dose interruptions and reductions in 9% and 14% of patients, respectively, and 3% of patients discontinued BALVERSA®. Dry eye symptoms occurred in 28% of patients during treatment with BALVERSA® and were Grade 3 in 6% of 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 BALVERSA® when CSR occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 in severity. For ocular adverse reactions, follow the dose modification guidelines.

To treat and prevent dry eyes, instruct patients to use the following at least every 2 hours during waking hours:

Icon of a blue water droplet

artificial tear substitute

OR
Icon of a blue eye with blue pupil.

hydrating or lubricating eye gels

OR
Icon of a blue ointment tube

hydrating or lubricating ointments

Hyperphosphatemia1

Increases in phosphate levels are a pharmacodynamic effect of BALVERSA® [see Pharmacodynamics (12.2) of the full Prescribing Information]. Hyperphosphatemia was reported as adverse reaction in 76% of patients treated with BALVERSA®. The median onset time for any grade event of hyperphosphatemia was 20 days (range: 8-116) after initiating BALVERSA®. Thirty-two percent of patients received phosphate binders during treatment with BALVERSA®.

Monitor for hyperphosphatemia and follow the dose modification guidelines when required.

Embryo-fetal toxicity1

Based on the mechanism of action and findings in animal reproduction studies, BALVERSA® can cause fetal harm when administered to a pregnant woman. In a rat embryo-fetal toxicity study, erdafitinib was embryotoxic and teratogenic at exposures less than the human exposures at all doses studied. Advise pregnant women 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 reactions1

Adverse Reactions Reported in ≥10% (Any Grade) or
≥5% (Grade 3-4) of Patients
Adverse Reaction BALVERSA® 8 mg daily (N=87)
All Grades (%) Grade 3-4 (%)
Any 100 67
Gastrointestinal disorders 92 24
Stomatitis 56 9
Diarrhea 47 2
Dry mouth 45 0
Constipation 28 1
Abdominal paina 23 2
Nausea 21 1
Vomiting 13 2
Metabolism and nutrition disorders 90 16
Decreased appetite 38 0
General disorders and administration site conditions 69 13
Fatigueb 54 10
Pyrexia 14 1
Skin and subcutaneous tissue disorders 75 16
Onycholysisc 41 10
Dry skind 34 0
Palmar-plantar erythrodysesthesia syndrome 26 6
Alopecia 26 0
Nail discoloration 11 0
Eye disorders 62 11
Dry eyee 28 6
Vision blurred 17 0
Lacrimation increased 10 0
Nervous system disorders 57 5
Dysgeusia 37 1
Infections and Infestations 56 20
Paronychia 17 3
Urinary tract infection 17 6
Conjunctivitis 11 0
Respiratory, thoracic, and mediastinal disorders 40 7
Oropharyngeal pain 11 1
Dyspneaf 10 2
Renal and urinary tract disorders 38 10
Hematuria 11 2
Musculoskeletal and connective tissue disorders 31 0
Musculoskeletal paing 20 0
Arthralgia 11 0
Investigations 44 5
Weight decreasedh 16 0

aIncludes abdominal pain, abdominal discomfort, abdominal pain upper, and abdominal pain lower.
bIncludes asthenia, fatigue, lethargy, and malaise.
cIncludes onycholysis, onychoclasis, nail disorder, nali dystrophy, and nail ridging.
dIncludes dry skin and xerostomia.
eIncludes dry eye and xerophthalmia, keratitis, foreign body sensation and corneal erosion.
fIncludes dyspnea and dyspnea exertional.
gIncludes back pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal chest pain, neck pain, pain in extremity.
hIncludes weight decreased and cachexia.

Most common adverse reactions including laboratory abnormalities ≥20%:

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 adverse reactions (>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.

  • An adverse reaction with a fatal outcome in 1% of patients was acute myocardial infarction.
  • Serious adverse reactions occurred in 41% of patients including eye disorders (10%).
  • Permanent discontinuation due to an adverse reaction occurred in 13% of patients. The most frequent reasons for permanent discontinuation included eye disorders (6%).
  • Dosage interruptions occurred in 68% of patients. The most frequent adverse reactions requiring dosage interruption included hyperphosphatemia (24%), stomatitis (17%), eye disorders (17%), and palmar-plantar erythrodysesthesia syndrome (8%).
  • Dose reductions occurred in 53% of patients. The most frequent adverse reactions for dose reductions included eye disorders (23%), stomatitis (15%), hyperphosphatemia (7%), palmar-plantar erythrodysesthesia syndrome (7%), paronychia (7%), and nail dystrophy (6%).

For information about Dosing and Dose Adjustments, please see section 2 of the full BALVERSA® Prescribing Information.

Laboratory abnormalities1

Laboratory Abnormalities Reported in ≥10% (All Grade) or ≥5% (Grade 3-4) of Patients
Treated With BALVERSA® 8 mg Once Daily (N=86*1
Laboratory Abnormality All Grades (%) Grade 3-4 (%)
Hematology    
Hemoglobin decreased 35 3
Platelets decreased 19 1
Leukocytes decreased 17 0
Neutrophils decreased 10 2
Chemistry    
Phosphate increased 76 1
Creatinine increased 52 5
Sodium decreased 40 16
Alanine aminotransferase increased 41 1
Alkaline phosphatase increased 41 1
Albumin decreased 37 0
Aspartate aminotransferase increased 30 0
Magnesium decreased 30 1
Phosphate decreased 24 9
Calcium increased 22 3
Potassium increased 16 0
Fasting glucose increased 10 0

*One of the 87 patients has no laboratory tests.

Reference

1. BALVERSA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.