The U.S. Food and Drug Administration granted accelerated approval to Balversa (erdafitinib), a treatment for adult patients with locally advanced or metastatic bladder cancer that has a type of susceptible genetic alteration known as FGFR3 or FGFR2, and that has progressed during or following prior platinum-containing chemotherapy. Patients should be selected for therapy with Balversa using an FDA-approved companion diagnostic device.
The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Bladder cancers are associated with genetic mutations that are present in the patient’s bladder or entire urothelium (the lining of the lower urinary tract).
Bladder cancer is the sixth most common cancer in the United States. Fibroblast growth factor (FGFR) alterations are present in approximately one in five patients with recurrent and refractory bladder cancer.
Erdafitinib, the active ingredient in BALVERSA, is a kinase inhibitor. The chemical name is N-(3,5-dimethoxyphenyl)-N’-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol4-yl)quinoxalin-6-yl]ethane-1,2-diamine. 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:
CLINICAL PHARMACOLOGY 12.1 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 also binds to RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, and VEGFR2. 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.
EFFICACY & SAFETY
The efficacy of Balversa was studied in a clinical trial that included 87 patients with locally advanced or metastatic bladder cancer, with FGFR3 or FGFR2 genetic alterations, that had progressed following treatment with chemotherapy. The overall response rate in these patients was 32.2%, with 2.3% having a complete response and almost 30% having a partial response. The response lasted for an average of approximately five-and-a-half months. About a quarter of patients in the study were previously treated with anti PD-L1/PD-1 therapy, which is a standard treatment for patients with locally advanced or metastatic bladder cancer. Responses to Balversa were seen in patients who had previously not responded to anti PD-L1/PD-1 therapy.
IMPORTANT SAFETY INFORMATION
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.
- 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.
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
- 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’)
- stomach (abdominal) pain
- 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 the FDA at 1-800-FDA-1088.
Keep BALVERSA™ 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.
Please click here to see full BALVERSA™ Prescribing Information.
Health care professionals are advised to tell male patients with female partners of reproductive potential to use effective contraception during treatment with Balversa and for one month after the last dose. Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with Balversa. Women who are pregnant or breastfeeding should not take Balversa because it may cause harm to a developing fetus or newborn baby. Balversa must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.
Balversa received an Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need using clinical trial data that is thought to predict a clinical benefit to patients. Further clinical trials are required to confirm Balversa’s clinical benefit and the sponsor is conducting or plans to conduct these studies. Balversa was also granted Breakthrough Therapy designation.
The FDA granted the approval of Balversa to Janssen Pharmaceutical.
The FDA also approved the therascreen FGFR RGQ RT-PCR Kit, developed by QIAGEN Manchester, Ltd., for use as a companion diagnostic with Balversa for this therapeutic indication.