Safety

The safety profile of BALVERSA^® was evaluated in a randomized, open-label, multicenter phase 3 study vs chemotherapy^1,2

The safety of BALVERSA® was evaluated in cohort 1 of the BLC3001 study that included patients with locally advanced unresectable or metastatic UC which had susceptible FGFR3 genetic alterations and were previously treated with a PD-1 or PD-L1 inhibitor. Patients were randomized to receieve either BALVERSA® (8 mg orally once daily with individualized up-titration to 9 mg) (n=135) or chemotherapy (docetaxel 75 mg/m² once every 3 weeks or vinflunine 320 mg/m² once every 3 weeks) (n=112). Among patients who received BALVERSA®, median duration of treatment was 4.8 months (range: 0.2 to 38 months).

• Clinically relevant adverse reactions in <15% patients who received BALVERSA® included nausea (15%), pyrexia (15%), epistaxis (13%), vomiting (10%), and arthralgia (10%)

Most common (>20%) adverse reactions, including laboratory abnormalities, in the pooled safety population (BALVERSA® vs chemotherapy):

Increased phosphate (76% vs 0%), nail disorders (70% vs 5%), stomatitis (56% vs 18%), diarrhea (63% vs 17%), increased creatinine (43% vs 17%), increased alkaline phosphate (54% vs 29%), increased alanine aminotransferase (46% vs 15%), decreased hemoglobin (50% vs 57%), decreased sodium (44% vs 25%), increased aspartate aminotransferase (44% vs 13%), fatigue (29% vs 42%), dry mouth (39% vs 3.6%), dry skin (27% vs 6%), decreased phosphate (34% vs 25%), decreased appetite (27% vs 21%), dysgeusia (30% vs 7%), constipation (27% vs 28%), increased calcium (27% vs 9%), dry eye (25% vs 3.6%), palmar-plantar erythrodysesthesia syndrome (30% vs 0.9%), increased potassium (24% vs 21%), alopecia (25% vs 24%), and central serous retinopathy (18% vs 0%).

• Fatal ARs 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%)

• Serious ARs occurred in 41% of patients who received BALVERSA®, including urinary tract infection (4.4%), hematuria (3.7%), hyponatremia (2.2%), and acute kidney injury (2.2%)

• Permanent discontinuation of BALVERSA® due to an AR occurred in 14% of patients. ARs resulting in permanent discontinuation included nail disorders (3%) and eye disorders (2.2%)

• Dosage interruptions of BALVERSA® due to an adverse reaction occurred in 72% of patients. The most frequent ARs leading to dosage interruptions 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. The most frequent ARs leading to dose reduction included (27%), stomatitis (19%), eye disorders (17%), palmar-plantar erythrodysesthesia syndrome (12%), diarrhea (7%), dry mouth (4.4%), and hyperphosphatemia (4.4%)

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

artificial tear substitute

OR

hydrating or lubricating eye gels

OR

hydrating or lubricating ointments

Visit the American Optometric Association website to refer your patient to an eye specialist.

Hyperphosphatemia and Soft Tissue Mineralization¹

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®.

In the pooled safety population, increased phosphate occurred in 71% 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. Restrict dietary phosphate intake (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. See Dosing & Administration for details on dose modifications for adverse reactions.

Based on the mechanism of action and findings in animal reproduction studies, BALVERSA® can cause fetal harm when administered to a pregnant patient. 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 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.