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Balversa (Erdafitinib Tablets): Side Effects, Uses, Dosage, Interactions, Warnings

Balversa

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 11/4/2024

Drug Summary

What Is Balversa?

Balversa (erdafitinib) is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that 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.

What Are Side Effects of Balversa?

Balversa may cause serious side effects including:

  • hives,
  • difficulty breathing,
  • swelling of your face, lips, tongue, or throat,
  • numbness or tingling around your mouth,
  • muscle stiffness,
  • body aches,
  • itching,
  • rash,
  • tiredness,
  • trouble sleeping,
  • nausea,
  • vomiting,
  • loss of appetite,
  • shortness of breath,
  • vision problems,
  • vision loss,
  • eye pain or redness,
  • painful or irritated eyelids,
  • feeling like something is in your eye,
  • watery eyes,
  • increased sensitivity to light,
  • pain or bleeding from your finger or toe nails,
  • separation of the nails from the skin (nail bed),
  • unusual breakage of your nails,
  • changes in nail color or texture, and
  • cracks or infection in your cuticles

Get medical help right away, if you have any of the symptoms listed above.

Common side effects of Balversa include:

  • inflammation of the mouth and lips,
  • fatigue,
  • diarrhea,
  • dry mouth,
  • separation nails from the nail bed,
  • infection around the fingernails or toenails,
  • decreased sodium,
  • decreased appetite,
  • changes in taste,
  • dry skin, decreased magnesium,
  • dry eye,
  • hair loss,
  • hand-foot syndrome redness,
  • swelling,
  • pain on the palms of the hands and/or the soles of the feet),
  • constipation,
  • abdominal pain,
  • increased calcium,
  • nausea,
  • musculoskeletal pain,
  • vomiting,
  • fever,
  • nail discoloration,
  • blurred vision,
  • increased tearing,
  • urinary tract infection (UTI),
  • conjunctivitis,
  • mouth or throat pain,
  • shortness of breath,
  • blood in the urine,
  • joint pain, and
  • weight loss

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheadedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Balversa

The recommended initial dosage of Balversa is 8 mg orally once daily with a dose increase to 9 mg daily if criteria are met.

What Drugs, Substances, or Supplements Interact with Balversa?

Balversa may interact with strong or moderate inhibitors or inducers of CYP2C9 or CYP3A4, serum phosphate level-altering agents, CYP3A4 substrates, OCT2 substrates, or P-gp substrates. Tell your doctor all medications and supplements you use.

Balversa During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Balversa; it may harm a fetus. Because of the potential for serious adverse reactions in a breastfed child, breastfeeding is not recommended while using Balversa and for one moth following the last dose

Additional Information

TOur Balversa (erdafitinib) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

Description for Balversa

Erdafitinib, the active ingredient in BALVERSA, is a kinase inhibitor. The chemical name is N-(3,5dimethoxyphenyl)-N’-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2diamine. Erdafitinib is a yellow powder. It is practically insoluble, or insoluble to freely soluble in organic solvents, and slightly soluble to practically insoluble, or insoluble in aqueous media over a wide range of pH values. The molecular formula is C25H30N6O2 and molecular weight is 446.56.

Chemical structure of erdafitinib is as follows:

BALVERSA (erdafitinib) Structural Formula  - Illustration

BALVERSA (erdafitinib) is supplied as 3 mg, 4 mg or 5 mg film-coated tablets for oral administration and contains the following inactive ingredients:

Tablet Core: Croscarmellose sodium, Magnesium stearate (from vegetable source), Mannitol, Meglumine, and Microcrystalline Cellulose.

Film Coating: (Opadry amb II): Glycerol monocaprylocaprate Type I, Polyvinyl alcohol-partially hydrolyzed, Sodium lauryl sulfate, Talc, Titanium dioxide, Iron oxide yellow, Iron oxide red (for the orange and brown tablets only), Ferrosoferric oxide/iron oxide black (for the brown tablets only).

Uses for Balversa

BALVERSA is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy.

Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA [see DOSAGE AND ADMINISTRATION and Clinical Studies].

Limitations Of Use

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 [see Clinical Studies].

Dosage for Balversa

Patient Selection

Select patients for the treatment of locally advanced or metastatic urothelial carcinoma with BALVERSA based on the presence of susceptible FGFR3 genetic alterations in tumor specimens as detected by an FDA-approved companion diagnostic [see Clinical Studies].

Information on FDA-approved tests for the detection of FGFR3 genetic alterations in urothelial cancer is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage And Schedule

The recommended starting dose of BALVERSA is 8 mg (two 4 mg tablets) orally once daily, with a dose increase to 9 mg (three 3 mg tablets) once daily based on tolerability, including hyperphosphatemia, at 14 to 21 days [see DOSAGE AND ADMINISTRATION].

Swallow tablets whole with or without food. If vomiting occurs any time after taking BALVERSA, the next dose should be taken the next day. Treatment should continue until disease progression or unacceptable toxicity occurs.

If a dose of BALVERSA is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for BALVERSA the next day. Extra tablets should not be taken to make up for the missed dose.

Dose Increase Based On Serum Phosphate Levels

Assess serum phosphate levels 14 to 21 days after initiating treatment. Increase the dose of BALVERSA to 9 mg once daily if serum phosphate level is < 9.0 mg/dL and there are no ocular disorders or Grade 2 or greater adverse reactions. Monitor phosphate levels monthly for hyperphosphatemia [see Pharmacodynamics].

Dose Modifications For Adverse Reactions

The recommended dose modifications for adverse reactions are listed in Table 1.

Table 1: BALVERSA Dose Reduction Schedule

Dose 1st dose reduction 2nd dose reduction 3rd dose reduction 4th dose reduction 5th dose reduction
9 mg → (three 3 mg tablets) 8 mg (two 4 mg tablets) 6 mg (two 3 mg tablets) 5 mg (one 5 mg tablet) 4 mg (one 4 mg tablet) Stop
8 mg → (two 4 mg tablets) 6 mg (two 3 mg tablets) 5 mg (one 5 mg tablet) 4 mg (one 4 mg tablet) Stop

Table 2 summarizes recommendations for dose interruption, reduction, or discontinuation of BALVERSA in the management of specific adverse reactions.

Table 2: Dose Modifications for Adverse Reactions

Adverse Reaction BALVERSA Dose Modification
Hyperphosphatemia
In all patients, restrict phosphate intake to 600-800 mg daily.
<6.99 mg/dL Continue BALVERSA at current dose.
7-8.99 mg/dL
  • Continue BALVERSA at current dose.
  • Start phosphate binder with food until phosphate level is <7 mg/dL.
  • Reduce the dose if serum phosphate remains ≥7 mg/dL for a period of 2 months or if clinically necessary.
9-10 mg/dL
  • Withhold BALVERSA with weekly reassessments until level returns to <7 mg/dL. Then restart BALVERSA at the same dose level.
  • Start phosphate binder with food until serum phosphate level returns to <7 mg/dL.
  • Reduce the dose for serum phosphate ≥9 mg/dL for a period of 1 month or if clinically necessary.
>10 mg/dL
  • Withhold BALVERSA with weekly reassessments until level returns to <7 mg/dL. Then may restart BALVERSA at the first reduced dose level.
  • If hyperphosphatemia (≥10 mg/dL) for >2 weeks, discontinue BALVERSA permanently.
  • Medical management of symptoms as clinically relevant.
Serum phosphate with life-threatening consequences; urgent intervention indicated (e.g., dialysis)
  • Discontinue BALVERSA permanently.
Central Serous Retinopathy (CSR)
Any

Withhold BALVERSA and perform an ophthalmic evaluation within 2 weeks:

  • If improving within 14 days, restart BALVERSA at the current dose.
  • If not improving within 14 days, withhold BALVERSA until improving; once improving, may resume at the next lower dose level. Upon restarting BALVERSA, monitor for recurrence every 1 to 2 weeks for a month. If recurs or has not improved after 4 weeks of withholding BALVERSA, consider permanent discontinuation.
Other Adverse Reactionsa
Grade 3 Withhold BALVERSA until resolves to Grade 1 or baseline, then may resume dose level lower.
Grade 4 Permanently discontinue.
a Dose adjustment graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEv5.0).

HOW SUPPLIED

Dosage Forms And Strengths

Tablets
  • 3 mg: Yellow, round biconvex, film-coated, debossed with “3” on one side; and “EF” on the other side.
  • 4 mg: Orange, round biconvex, film-coated, debossed with “4” on one side; and “EF” on the other side.
  • 5 mg: Brown, round biconvex, film-coated, debossed with “5” on one side; and “EF” on the other side.

Storage And Handling

BALVERSA® (erdafitinib) tablets are available in the strengths and packages listed below:

3 mg tablets: Yellow, round biconvex, film-coated, debossed with “3” on one side and “EF” on the other side.

Bottle of 56-tablets with child resistant closure (NDC 59676-030-56).
Bottle of 84-tablets with child resistant closure (NDC 59676-030-84).

4 mg tablets: Orange, round biconvex, film-coated, debossed with “4” on one side and “EF” on the other side.

Bottle of 28-tablets with child resistant closure (NDC 59676-040-28).
Bottle of 56-tablets with child resistant closure (NDC 59676-040-56).

5 mg tablets: Brown, round biconvex, film-coated, debossed with “5” on one side and “EF” on the other side.

Bottle of 28-tablets with child resistant closure (NDC 59676-050-28).

Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted between 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature].

Product of Switzerland Manufactured for: Janssen Products, LP Horsham, PA 19044, USA. Revised: Jan 2024

Warnings for Balversa

Included as part of the PRECAUTIONS section.

Precautions for Balversa

Ocular Disorders

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

In the pooled safety population [see ADVERSE REACTIONS], 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 [see DOSAGE AND ADMINISTRATION].

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].

In the pooled safety population [see ADVERSE REACTIONS], 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. 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 according to Table 2 [see DOSAGE AND ADMINISTRATION].

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 woman. In an embryo-fetal toxicity study, oral administration of erdafitinib to pregnant rats during the period of organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum human recommended dose based on area under the curve (AUC). 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 [see Use In Specific Populations and CLINICAL PHARMACOLOGY].

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).

FGFR Genetic Alterations

Advise patients that evidence of a susceptible FGFR3 mutation or gene fusion within the tumor specimen is necessary to identify patients for whom treatment is indicated [see DOSAGE AND ADMINISTRATION].

Ocular Disorders

Advise patients to contact their healthcare provider if they experience any visual changes [see WARNINGS AND PRECAUTIONS]. In order to prevent or treat dry eyes, advise patients to use artificial tear substitutes, hydrating or lubricating eye gels or ointments frequently, at least every 2 hours during waking hours [see DOSAGE AND ADMINISTRATION].

Skin, Mucous Or Nail Disorders

Advise patients to contact their healthcare provider if they experience progressive or intolerable skin, mucous or nail disorders [see ADVERSE REACTIONS].

Hyperphosphatemia And Soft Tissue Mineralization

Inform patients that BALVERSA may cause hyperphosphatemia and soft tissue mineralization. Advise patients to immediately inform their healthcare provider of painful skin lesions or any symptoms related to acute change in phosphate levels such as muscle cramps, numbness, or tingling around the mouth [see WARNINGS AND PRECAUTIONS].

Advise patients that their healthcare provider will assess their serum phosphate level between 14 and 21 days of initiating treatment and will adjust the dose if needed [see WARNINGS AND PRECAUTIONS]. Advise patients to restrict phosphate intake to 600-800 mg daily. During this initial phosphate-assessment period, advise patients to avoid concomitant use with agents that can alter serum phosphate levels. Advise patients that, after the initial phosphate assessment period, monthly phosphate level monitoring for hyperphosphatemia should be performed during treatment with BALVERSA [see DRUG INTERACTIONS].

Drug Interactions

Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, and herbal products [see DRUG INTERACTIONS].

Dosing Instructions

Instruct patients to swallow the tablets whole once daily with or without food. If vomiting occurs any time after taking BALVERSA, advise patients to take the next dose the next day [see DOSAGE AND ADMINISTRATION].

Missed Dose

If a dose is missed, advise patients to take the missed dose as soon as possible. Resume the regular daily dose schedule for BALVERSA the next day. Extra tablets should not be taken to make up for the missed dose [see DOSAGE AND ADMINISTRATION].

Embryo-Fetal Toxicity

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females to inform their healthcare providers of a known or suspected pregnancy [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]. Advise female patients of reproductive potential to use effective contraception during treatment and for one month after the last dose of BALVERSA. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose of BALVERSA [see Use In Specific Populations].

Lactation

Advise females not to breastfeed during treatment with BALVERSA and for one month after the last dose [see Use In Specific Populations].

Infertility

Advise females of reproductive potential that BALVERSA may impair fertility [see Use In Specific Populations].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, And Impairment Of Fertility

Carcinogenicity studies have not been conducted with erdafitinib.

Erdafitinib was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro micronucleus or an in vivo rat bone marrow micronucleus assay.

Fertility studies in animals have not been conducted with erdafitinib. In the 3-month repeat-dose toxicity study, erdafitinib showed effects on female reproductive organs (necrosis of the ovarian corpora lutea) in rats at an exposure less than the human exposure (AUC) at maximum recommended human dose.

Use In Specific Populations

Pregnancy

Risk Summary

Based on the mechanism of action and findings in animal reproduction studies, BALVERSA can cause fetal harm when administered to a pregnant woman [see CLINICAL PHARMACOLOGY]. There are no available data on BALVERSA use in pregnant women to inform a drug-associated risk. Oral administration of erdafitinib to pregnant rats during organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum recommended human dose based on AUC (see Data). Advise pregnant women and females of reproductive potential of the potential risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

In an embryo-fetal toxicity study, erdafitinib was orally administered to pregnant rats during the period of organogenesis. Doses ≥4 mg/kg/day (at total maternal exposures <0.1% of total human exposures at the maximum recommended human dose based on AUC) produced embryo-fetal death, major blood vessel malformations and other vascular anomalies, limb malformations (ectrodactyly, absent or misshapen long bones), an increased incidence of skeletal anomalies in multiple bones (vertebrae, sternebrae, ribs), and decreased fetal weight.

Lactation

Risk Summary

There are no data on the presence of erdafitinib in human milk, or the effects of erdafitinib on the breastfed child, or on milk production. Because of the potential for serious adverse reactions from erdafitinib in a breastfed child, advise lactating women not to breastfeed during treatment with BALVERSA and for one month following the last dose.

Females And Males Of Reproductive Potential

BALVERSA can cause fetal harm when administered to a pregnant woman [see Use In Specific Populations].  

Pregnancy Testing

Verify pregnancy status in females of reproductive potential prior to initiating treatment with BALVERSA.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with BALVERSA and for one month after the last dose.

Males

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.

Infertility

Females

Based on findings from animal studies, BALVERSA may impair fertility in females of reproductive potential [see Nonclinical Toxicology].

Pediatric Use

Safety and effectiveness of BALVERSA in pediatric patients have not been established.

In 4 and 13-week repeat-dose toxicology studies in rats and dogs, toxicities in bone and teeth were observed at an exposure less than the human exposure (AUC) at the maximum recommended human dose. Chondroid dysplasia/metaplasia were reported in multiple bones in both species, and tooth abnormalities included abnormal/irregular denting in rats and dogs and discoloration and degeneration of odontoblasts in rats.

Geriatric Use

Of the 479 patients treated with BALVERSA in clinical studies, 40% of patients were less than 65 years old, 40% of patients were 65 years to 74 years old, and 20% were 75 years old and over.

Patients 65 years of age and older treated with BALVERSA experienced a higher incidence of adverse reactions requiring treatment discontinuation than younger patients. In clinical trials, the incidence of treatment discontinuations of BALVERSA due to adverse reactions was 10% in patients younger than 65 years, 20% in patients ages 65-74 years, and 35% in patients 75 years or older.

No overall difference in efficacy was observed between these patients and younger patients [see Clinical Studies].

CYP2C9 Poor Metabolizers

CYP2C9*3/*3 Genotype: Erdafitinib plasma concentrations are predicted to be higher in patients with the CYP2C9*3/*3 genotype. Monitor for increased adverse reactions in patients who are known or suspected to have CYP2C9*3/*3 genotype [see Pharmacogenomics].

Overdose Information for Balversa

No Information provided

Contraindications for Balversa

None.

Clinical Pharmacology for Balversa

Mechanism Of Action

Erdafitinib is a kinase inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3 and FGFR4 based on in vitro data. Erdafitinib inhibited FGFR phosphorylation and signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions. Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer.

Pharmacodynamics

Cardiac Electrophysiology

Based on evaluation of QTc interval in an open-label, dose escalation and dose expansion study in 187 patients with cancer, erdafitinib had no large effect (i.e., > 20 ms) on the QTc interval.

Serum Phosphate

FGFR inhibition by BALVERSA increases serum phosphate level [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS].

Pharmacokinetics

Following administration of BALVERSA 8 mg once daily, the mean (coefficient of variation [CV%]) erdafitinib steady-state maximum plasma concentration (Cmax), area under the curve (AUCtau), and minimum plasma concentration (Cmin) were 1,399 ng/mL (51%), 29,268 ng·h/mL (60%), and 936 ng/mL (65%), respectively.

Following single and repeat once daily dosing of BALVERSA, erdafitinib exposure (Cmax and AUC) increased proportionally across the dose range of 0.5 to 12 mg (0.06 to 1.3 times the maximum approved recommended dose). Steady state was achieved after 2 weeks with once daily dosing with a mean accumulation ratio of 4-fold.

Absorption

Median time to achieve peak plasma concentration (tmax) was 2.5 hours (range: 2 to 6 hours).

Effect Of Food

No clinically meaningful differences in erdafitinib exposure was observed following administration of BALVERSA with a high-fat and high-calorie meal (800 calories to 1,000 calories with approximately 50% of total caloric content of the meal from fat).

Distribution

The mean apparent volume of distribution of erdafitinib was 29 L.

Erdafitinib protein binding was 99.7% in patients, primarily to alpha-1-acid glycoprotein.

Elimination

The mean total apparent clearance (CL/F) of erdafitinib was 0.362 L/h.

The mean effective half-life of erdafitinib was 59 hours.

Metabolism

Erdafitinib is primarily metabolized by CYP2C9 and CYP3A4. The contribution of CYP2C9 and CYP3A4 in the total clearance of erdafitinib is estimated to be 39% and 20%, respectively. Unchanged erdafitinib was the major drug-related moiety in plasma, there were no circulating metabolites.

Excretion

Following a single oral dose of radiolabeled erdafitinib, approximately 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged).

Specific Populations

No clinically meaningful effects on erdafitinib exposure were observed based on age (21-92 years), sex, race (White, Hispanic or Asian), body weight (36-166 kg), mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, or mild to moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m²). Limited data are available in patients with severe (Child-Pugh C) hepatic impairment and in patients with severe renal impairment. The pharmacokinetics of erdafitinib in patients with renal impairment requiring dialysis is unknown.

Drug Interaction Studies

Clinical Studies

Effect Of Other Drugs On Erdafitinib

Moderate CYP2C9 Inhibitors

Erdafitinib mean ratios for Cmax and AUCinf were 121% and 148%, respectively, when BALVERSA was co-administered with fluconazole, a moderate CYP2C9 and CYP3A4 inhibitor, relative to BALVERSA administered alone.

Strong CYP3A4 Inhibitors

Erdafitinib mean ratios for Cmax and AUCinf were 105% and 134%, respectively, when BALVERSA was co-administered with itraconazole (a strong CYP3A4 inhibitor and P-gp inhibitor) relative to BALVERSA alone.

CYP3A4/2C9 Inducers

Erdafitinib mean ratios for Cmax and AUCinf were 78% and 45%, respectively, when BALVERSA was co-administered with carbamazepine (a strong CYP3A4 and weak CYP2C9 inducer) relative to BALVERSA alone.

Effect Of Erdafitinib On Other Drugs

CYP3A4 Substrates

No clinically meaningful effect on the exposure of midazolam (a CYP3A4 substrate) was observed following coadministration with BALVERSA.

OCT2 Substrates

No clinically meaningful effect on the exposure of metformin (an OCT2 substrate) was observed following coadministration with BALVERSA.

In Vitro Studies

CYP Substrates

Erdafitinib is a time dependent inhibitor and inducer of CYP3A4. Erdafitinib is not an inhibitor of other major CYP isozymes at clinically relevant concentrations.

Transporters

Erdafitinib is a substrate and inhibitor of P-gp. P-gp inhibitors are not expected to affect erdafitinib exposure to a clinically relevant extent. Erdafitinib is an inhibitor of OCT2.

Erdafitinib does not inhibit BCRP, OATP1B, OATP1B3, OAT1, OAT3, OCT1, MATE-1, or MATE-2K at clinically relevant concentrations.

Acid-Lowering Agents

Erdafitinib has adequate solubility across the pH range of 1 to 7.4. Acid-lowering agents (including antacids, H2-antagonistsand proton pump inhibitors) are not expected to affect the bioavailability of erdafitinib.

Pharmacogenomics

CYP2C9 activity is reduced in individuals with genetic variants, such as the CYP2C9*2 and CYP2C9*3 polymorphisms. Erdafitinib exposure was similar in subjects with CYP2C9*1/*2 and *1/*3 genotypes relative to subjects with CYP2C9*1/*1 genotype (wild type). No data are available in subjects characterized by other genotypes (e.g., *2/*2, *2/*3, *3/*3). Simulation suggested no clinically meaningful differences in erdafitinib exposure in subjects with CYP2C9*2/*2 and *2/*3 genotypes. The exposure of erdafitinib is predicted to be 50% higher in subjects with the CYP2C9*3/*3 genotype, estimated to be present in 0.4% to 3% of the population among various ethnic groups.

Clinical Studies

Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations

The efficacy of BALVERSA was evaluated in Study BLC3001 (NCT03390504) Cohort 1, a randomized, open-label, multicenter study in which 266 patients with advanced urothelial cancer harboring selected FGFR3 alterations were randomized 1:1 to receive BALVERSA (8 mg with titration up to 9 mg) versus chemotherapy (docetaxel 75 mg/m² once every 3 weeks or vinflunine 320 mg/m² once every 3 weeks) until unacceptable toxicity or progression. Randomization was stratified by region (North America vs. Europe vs. rest of world), Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 vs. 2) and visceral or bone metastases (yes vs. no). All patients needed to have had disease progression after 1 or 2 prior treatments, at least 1 of which included a PD-1 or PD-L1 inhibitor. FGFR3 genetic alterations were identified from tumor tissue in a central laboratory by the QIAGEN therascreen® FGFR RGQ RT-Polymerase Chain Reaction (PCR) kit in 75% of patients while the remainder (25%) were identified by local next generation sequencing (NGS) assays.

The major efficacy outcome measures were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) assessed by investigator using RECIST (Response Evaluation Criteria in Solid Tumors) Version 1.1.

The median age was 67 years (range: 32 to 86 years) and 71% were male; 54% were White, 29% Asian, 0.4% Black, 0.4% multiple races, 16% not reported; 2% were Hispanic/Latino; and baseline ECOG performance status was 0 (43%), 1 (48%), or 2 (9%). Eighty-one percent of patients had FGFR3 mutations, 17% had fusions, and 2% had both mutations and fusions. Ninety-five percent of patients had pure transitional cell carcinoma (TCC) and 5% had TCC with other histologic variants. The primary tumor location was the upper tract for 33% of subjects and lower tract for 67%; 74% of patients had visceral or bone metastases. Eighty-eight percent of patients received platinum-containing chemotherapy previously. PD-1 or PD-L1 inhibitor therapy was received only in the neoadjuvant or adjuvant setting in 7% of patients.

Statistically significant improvements in OS, PFS, and ORR were demonstrated for BALVERSA compared with chemotherapy.

Table 9 and Figures 1 and 2 summarize the efficacy results for BLC3001 Cohort 1.

Table 9: Efficacy Results for Study BLC3001 Cohort 1

BALVERSA
N=136
Chemotherapy
N=130
Overall Survival (OS)
Number of events (%) 77 (56.6%) 78 (60.0%)
Mediana, months (95% CI) 12.1 (10.3, 16.4) 7.8 (6.5, 11.1)
Hazard ratiob (95% CI) 0.64 (0.47, 0.88)
p-valuec 0.0050
Progression-free survival (PFS)
Number of events (%) 101 (74.3%) 90 (69.2%)
Mediana, months (95% CI) 5.6 (4.4, 5.7) 2.7 (1.8, 3.7)
Hazard ratiob (95% CI) 0.58 (0.44, 0.78)
p-valuec 0.0002
Objective response rate (ORR)
ORR (95% CI) 35.3% (27.3, 43.9) 8.5% (4.3, 14.6)
p-valued <0.001
Complete response, CR (%) 5.1% 0.8%
Partial response, PR (%) 30.1% 7.7%
All p-values reported are 2-sided and compared with 0.019 of the allocated alpha for the interim analysis.
a Based on Kaplan-Meier estimates
b Based on an unstratified Cox proportional hazard model
c Based on an unstratified log-rank test
d p-value is estimated using Cochran-Haenszel (CMH) test with ECOG performance status (0 or 1 vs 2) as a stratification factor.
ORR = confirmed objective response (CR + PR)
CI = Confidence Interval

Figure 1: Kaplan-Meier Plot of Overall Survival (Study BLC3001 Cohort 1)

Kaplan-Meier Plot of Overall Survival (Study
BLC3001 Cohort 1) Illustration

Figure 2: Kaplan-Meier Plot of Progression-free Survival (Study BLC3001 Cohort 1)

Kaplan-Meier Plot of Progression-free Survival
(Study BLC3001 Cohort 1) Illustration

Study BLC3001 Cohort 2

Study BLC3001 (NCT03390504) Cohort 2 was a multicenter, open-label, randomized study in 351 patients with locally advanced or metastatic urothelial carcinoma with selected FGFR3 alterations who received 1 prior line of systemic therapy and no prior PD-1 or PD-L1 inhibitor. Patients were randomized 1:1 to receive BALVERSA (8 mg with titration up to 9 mg) or pembrolizumab 200 mg every 3 weeks. The study did not meet its major efficacy outcome measure for superiority of OS at the pre-specified final analysis. The OS hazard ratio (HR) was 1.18 (95% CI: 0.92, 1.51; p=0.18), median 10.9 (95% CI: 9.2, 12.6) months for BALVERSA versus 11.1 (95% CI: 9.7, 13.6) months for pembrolizumab [see INDICATIONS AND USAGE].

Study BLC2001

Study BLC2001 (NCT02365597) was a multicenter, open-label, single-arm study to evaluate the efficacy and safety of BALVERSA in patients with locally advanced or metastatic urothelial carcinoma (mUC). FGFR mutation status for screening and enrollment of patients was determined by a clinical trial assay (CTA). The efficacy population consists of a cohort of eighty-seven patients who were enrolled in this study with disease that had progressed on or after at least one prior chemotherapy and that had at least 1 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 the CTA performed at a central laboratory. Tumor samples from 69 patients were tested retrospectively by the QIAGEN therascreen® FGFR RGQ RT-PCR Kit, which is the FDA-approved test for selection of patients with mUC for BALVERSA.

Patients received a starting dose of BALVERSA at 8 mg once daily with a dose increase to 9 mg once daily in patients whose serum phosphate levels were below the target of 5.5 mg/dL between days 14 and 17; a dose increase occurred in 41% of patients. BALVERSA was administered until disease progression or unacceptable toxicity. The major efficacy outcome measures were ORR and duration of response (DoR), as determined by blinded independent review committee (BIRC) according to RECIST v1.1.

The median age was 67 years (range: 36 to 87 years), 79% were male, and 74% were Caucasian. Most patients (92%) had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Sixty-six percent of patients had visceral metastases. Eighty-four (97%) patients received at least one of cisplatin or carboplatin previously. Fifty-six percent of patients only received prior cisplatin-based regimens, 29% received only prior carboplatin-based regimens, and 10% received both cisplatin and carboplatin-based regimens. Three (3%) patients had disease progression following prior platinum-containing neoadjuvant or adjuvant therapy only. Twenty-four percent of patients had been treated with prior anti PD-L1/PD-1 therapy.

Efficacy results are summarized in Table 10 and Table 11. ORR was 32.2%. Responders included patients who had previously not responded to anti PD-L1/PD-1 therapy.

Table 10: Efficacy Results

Endpoint BIRCa Assessment
N=87
ORR (95% CI) 32.2% (22.4, 42.0)
Complete response (CR) 2.3%
Partial response (PR) 29.9%
Median DoR in months (95% CI) 5.4 (4.2, 6.9)
a BIRC: Blinded Independent Review Committee
ORR = CR + PR
CI = Confidence Interval

Table 11: Efficacy Results by FGFR Genetic Alteration

FGFR3 Point Mutation BIRCa Assessment
N=64
ORR (95% CI) 40.6% (28.6, 52.7)
FGFR3 Fusion b c N=18
ORR (95% CI) 11.1% (0, 25.6)
FGFR2 Fusion c N=6
ORR 0
a BIRC: Blinded Independent Review Committee
b Both responders had FGFR3-TACC3_V1 fusion
c One patient with a FGFR2-CASP7/FGFR3-TACC3_V3 fusion is reported in both FGFR2 fusion and FGFR3 fusion above
ORR = CR + PR
CI = Confidence Interval

Patient Information for Balversa

BALVERSA®
(bal-VER-sah)
(erdafitinib) tablets

What is BALVERSA?

BALVERSA is a prescription medicine used to treat adults with bladder cancer (urothelial cancer) that has spread or cannot be removed by surgery:

  • which has a certain type of abnormal FGFR gene, and
  • who have tried at least one other medicine by mouth or injection (systemic therapy) that did not work or is no longer working.

Your healthcare provider will test your cancer for certain types of abnormal FGFR genes and make sure that BALVERSA is right for you.

BALVERSA is not recommended for the treatment of people who are eligible for and have not received prior PD-1 or PDL1 inhibitor therapy.

It is not known if BALVERSA is safe and effective in children.

Before taking BALVERSA tell your healthcare provider about all of your medical conditions, including if you:

  • have vision or eye problems.
  • are pregnant or plan to become pregnant. BALVERSA can harm your unborn baby. You should not become pregnant during treatment with BALVERSA.

Females who can become pregnant:

    • Your healthcare provider may do a pregnancy test before you start treatment with BALVERSA.
    • You should use effective birth control during treatment and for 1 month after the last dose of BALVERSA. Talk to your healthcare provider about birth control methods that may be right for you.
    • Tell your healthcare provider right away if you become pregnant or think you may be pregnant.

Males with female partners who can become pregnant:

    • You should use effective birth control when sexually active during treatment with BALVERSA and for 1 month after the last dose.
  • are breastfeeding or plan to breastfeed. Do not breastfeed during treatment and for 1 month after the last dose of BALVERSA.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I take BALVERSA?

  • Take BALVERSA exactly as your healthcare provider tells you.
  • Take BALVERSA 1 time each day.
  • Swallow BALVERSA tablets whole with or without food.
  • Your healthcare provider may change your dose of BALVERSA, temporarily stop or completely stop treatment if you get certain side effects.
  • If you miss a dose of BALVERSA, take the missed dose as soon as possible on the same day. Take your regular dose of BALVERSA the next day. Do not take more BALVERSA than prescribed to make up for the missed dose.
  • If you vomit after taking BALVERSA, do not take another BALVERSA tablet. Take your regular dose of BALVERSA the next day.

What are the possible side effects of BALVERSA?

BALVERSA may cause serious side effects, including:

  • Eye problems. Eye problems are common with BALVERSA but can also be serious. Eye problems include dry or inflamed eyes, inflamed cornea (front part of the eye) and disorders of the retina, an internal part of the eye. Tell your healthcare provider right away if you develop blurred vision, loss of vision or other visual changes. You should use artificial tear substitutes, hydrating or lubricating eye gels or ointments at least every 2 hours during waking hours to help prevent dry eyes. During treatment with BALVERSA, your healthcare provider will send you to see an eye specialist.
  • High phosphate levels in the blood (hyperphosphatemia). Hyperphosphatemia is common with BALVERSA but can also be serious. High levels of phosphate in your blood may lead to build-up of minerals such as calcium in different tissues in your body. Your healthcare provider will check your blood phosphate level between 14 and 21 days after starting treatment with BALVERSA, and then monthly.
    • Your healthcare provider may prescribe changes in your diet or phosphate lowering therapy, or change or stop treatment with BALVERSA if needed.
    • Tell your healthcare provider right away if you develop painful skin lesions, any muscle cramps, or numbness or tingling around your mouth.

The most common side effects of BALVERSA include:

  • nails separate from the bed or poor formation of the nail
  • dry skin
  • decreased phosphate in the blood
  • mouth sores
  • decreased appetite
  • diarrhea
  • change in sense of taste
  • increased level of creatinine in the blood
  • constipation
  • increased level of the enzyme alkaline phosphatase in the blood
  • increased level of calcium in the blood
  • dry eye
  • change in liver function
  • redness, swelling, peeling or tenderness, mainly on the hands or feet (hand-foot syndrome)
  • decreased red blood cells (anemia)
  • decreased salt (sodium) levels in the blood
  • increased level of potassium in the blood
  • tiredness
  • hair loss
  • dry mouth
  • fluid buildup behind the retina in your eye

Tell your healthcare provider right away if you develop any nail or skin problems including nails separating from the nail bed, nail pain, nail bleeding, breaking of the nails, color or texture changes in your nails, infected skin around the nail, an itchy skin rash, dry skin, or cracks in the skin.

BALVERSA may affect fertility in females who are able to become pregnant. Talk to your healthcare provider if this is a concern for you.

These are not all of the possible side effects of BALVERSA. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store BALVERSA?

  • Store BALVERSA tablets at room temperature between 68°F to 77°F (20°C to 25°C).

Keep BALVERSA and all medicines out of the reach of children.

General information about the safe and effective use of BALVERSA.

Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use BALVERSA for a condition for which it was not prescribed. Do not give BALVERSA to other people, even if they have the same symptoms that you have. It may harm them. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about BALVERSA that is written for healthcare professionals.

What are the ingredients in BALVERSA?

Active ingredient: erdafitinib

Inactive ingredients:

Tablet Core: Croscarmellose sodium, Magnesium stearate (from vegetable source), Mannitol, Meglumine, and Microcrystalline Cellulose.

Film Coating (Opadry amb II): Glycerol monocaprylocaprate Type I, Polyvinyl alcohol-partially hydrolyzed, Sodium lauryl sulfate, Talc, Titanium dioxide, Iron oxide yellow, Iron oxide red (for the orange and brown tablets only), Ferrosoferric oxide/iron oxide black (for the brown tablets only).

This Patient Information has been approved by the U.S. Food and Drug Administration.

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.