BALVERSA (Page 5 of 6)

12.5 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.

13 NONCLINICAL TOXICOLOGY

13.1 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.

14 CLINICAL STUDIES

14.1 Urothelial Carcinoma with Susceptible FGFR Genetic Alterations

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). Fibroblast growth factor receptor (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 objective response rate (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 7 and Table 8. Overall response rate was 32.2%. Responders included patients who had previously not responded to anti PD-L1/PD-1 therapy.

Table 7: Efficacy Results
BIRC * assessment
Endpoint N=87
ORR = CR + PRCI = Confidence Interval
*
BIRC: Blinded Independent Review Committee
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)
Table 8: Efficacy Results by FGFR Genetic Alteration
BIRC * assessment
ORR = CR + PRCI = Confidence Interval
*
BIRC: Blinded Independent Review Committee
Both responders had FGFR3-TACC3_V1 fusion
One patient with a FGFR2-CASP7/FGFR3-TACC3_V3 fusion is reported in both FGFR2 fusion and FGFR3 fusion above
FGFR3 Point Mutation N=64
ORR (95% CI) 40.6% (28.6, 52.7)
FGFR3 Fusion , N=18
ORR (95% CI) 11.1% (0, 25.6)
FGFR2 Fusion N=6
ORR 0

16 HOW SUPPLIED/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–25°C (68°F–77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

17 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 or FGFR2 mutation or gene fusion within the tumor specimen is necessary to identify patients for whom treatment is indicated [see Dosage and Administration (2.1)].

Ocular disorders: Advise patients to contact their healthcare provider if they experience any visual changes [see Warnings and Precautions (5.1)]. 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 (2.3)].

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 (6.1)].

Hyperphosphatemia: 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 (5.2)]. 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 (7.1)].

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 (7.1, 7.2)].

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 (2.1)].

Missed dose: If a dose is missed, advise patients to take the missed 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 (2.3)].

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 Warning and Precautions (5.3) and Use in Specific Population (8.1)]. 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 (8.3)].

Lactation: Advise females not to breastfeed during treatment with BALVERSA and for one month after the last dose [see Use in Specific Populations (8.2)].

Product of Switzerland

Manufactured for:
Janssen Products, LPHorsham, PA 19044

Under license from Astex Therapeutics Limited.

©2019 Janssen Pharmaceutical Companies

This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: April 2020
PATIENT INFORMATIONBALVERSA® (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 chemotherapy medicine that contains platinum, and it 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.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. Your healthcare provider will check your blood phosphate level between 14 and 21 days after starting treatment with BALVERSA, and then monthly, and may change your dose if needed.
The most common side effects of BALVERSA include:
  • mouth sores
  • feeling tired
  • change in kidney function
  • diarrhea
  • dry mouth
  • nails separate from the bed or poor formation of the nail
  • change in liver function
  • low salt (sodium) levels
  • decreased appetite
  • change in sense of taste
  • low red blood cells (anemia)
  • dry skin
  • dry eyes
  • hair loss
  • redness, swelling, peeling or tenderness, mainly on the hands or feet (‘hand-foot syndrome’)
  • constipation
  • stomach (abdominal) pain
  • nausea
  • muscle pain
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 possible side effects of BALVERSA. For more information, ask your healthcare provider or pharmacist.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 healthcare provider for information about BALVERSA that is written for healthcare professionals.
What are the ingredients in BALVERSA?Active ingredient: erdafitinibInactive 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).Manufactured by: Janssen-Cilag SpA, Latina, ItalyManufactured for: Janssen Products, LP, Horsham, PA 19044© 2019 Janssen Pharmaceutical CompaniesFor more information call Janssen Products, LP at 1-800-526-7736 (1-800-JANSSEN) or go to www.BALVERSA.com.

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