Balversa
Balversa Uses, Dosage, Side Effects, Food Interaction and all others data.
In early April of 2019, the US FDA approved Janssen Pharmaceutical Companies' brand name Balversa (erdafitinib) as the first-ever fibroblast growth factor receptor (FGFR) kinase inhibitor indicated for patients with locally advanced or metastatic urothelial carcinoma, with susceptible FGFR3 or FGFR2 genetic alterations, that has progressed during or following platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy . At the same time, the FDA also approved the therascreen FGFR RGQ RT-PCR Kit (Qiagen) for utilization as a companion diagnostic with erdafitinib for selecting patients for the indicated therapy .
Balversa's innovation lies in the fact that it is the first personalized treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer, which demonstrates the design of erdafitinib in developing more personalized and precision medicines with the capacity to target cancer treatment to a patient's specific genetic mutation . Considering urothelial cancer is statistically the fourth most common kind of cancer in the world , the introduction of erdafitinib offers a welcome new option in the ever-expanding therapeutic tool kit to treat such prevalent medical conditions.
Nevertheless, although erdafitinib was granted Breakthrough Therapy designation and Accelerated Approval from the FDA so as to allow the agency to focus on and expedite the approval process for a medication indicated for a serious condition that fills an unmet medical need using clinical trial data that is believed to predict a genuine clinical benefit for patients with the given condition, such designations mean further ongoing clinical trials are necessary to confirm the clinical benefit of erdafitinib going forward .
| Trade Name | Balversa |
| Availability | Prescription only |
| Generic | Erdafitinib |
| Erdafitinib Other Names | Erdafitinib |
| Related Drugs | Keytruda, pembrolizumab, doxorubicin, cisplatin, Opdivo, nivolumab, atezolizumab, Adriamycin, mitomycin, Tecentriq |
| Weight | 3mg, 4mg, 5mg, |
| Type | Oral tablet |
| Formula | C25H30N6O2 |
| Weight | Average: 446.555 Monoisotopic: 446.24302423 |
| Protein binding | The protein binding recorded for erdafitinib is approximately 99.8%, and it was determined to be primarily bound to alpha-1-acid glycoprotein . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Canada, United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Balversa is a fibroblast growth factor receptor tyrosine kinase inhibitor used to treat locally advanced or metastatic urothelial carcinoma.
Balversa is a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor that is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma that has: i) susceptible FGFR3 or FGFR2 genetic alterations and has , ii) progressed during or following at least one line of prior platinum-containing chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy .
The selection of patients for the treatment of locally advanced or metastatic urothelial carcinoma with erdafitinib should be based on the presence of susceptible FGFR genetic alterations in tumor specimens as detected by an FDA-approved companion diagnostic like the FDA approved therascreen FGFR RGQ RT-PCR Kit as developed by QIAGEN .
This above indication is approved under accelerated approval by the US FDA based on tumor response rate . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials .
Balversa is also used to associated treatment for these conditions: Locally Advanced, Susceptible FGFR3 or FGFR2 genetic alterations, Condition has progressed during or following at least one line of prior platinum- containing chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy urothelial carcinoma, Metastatic Susceptible FGFR3 or FGFR2 genetic alterations, Condition has progressed during or following at least one line of prior platinum- containing chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy Metastatic Urothelial Carcinoma
How Balversa works
Urothelial cancer is statistically the fourth most common kind of cancer in the world . In general, such urothelial cancers originate in the urothelium - or the transitional epithelium - a membrane that covers the renal pelvis to the ureter, the bladder, and the proximal two-thirds of the urethra . While 90 to 95% of urothelial cancers are bladder cancers and the other 5 to 10% are upper tract urothelial cancers, the bladder cancers can also be either superficial or invasive (either not having or having invaded the deeper layers of the bladder) .
Moreover, fibroblast growth factor receptor (FGFR) is a transmembrane protein that is expressed ubiquitously in normal tissues and is involved in various endogenous bio-physiological processes including the homeostasis of phosphate and vitamin D, cell proliferation, cell anti-apoptotic signaling, and cell migration in a variety of cell types . Concurrently, genetic mutations or changes like deregulation of FGFR pathways and FGFR aberrations such as gene amplification, point mutations, and chromosomal translocations have been implicated in the pathogenesis of urothelial cancer, including the possibility of such changes to all four FGFR genes (FGFR1, FGFR2, FGFR3, and FGFR4) . Changes to the FGFR genes are consequently thought to promote cell proliferation, migration, angiogenesis, and anti-apoptosis in many cancers including urothelial cancer .
Balversa is subsequently an oral selective pan-FGFR kinase inhibitor that binds to and inhibits the enzymatic activity of expressed FGFR1, FGFR2, FGFR3, and FGFR4 based on in vitro data . In particular, erdafitinib demonstrates inhibition of FGFR phosphorylation and signaling as well as decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions . Balversa demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer .
Toxicity
Based on the mechanism of action and findings in animal reproduction studies, erdafitinib can cause fetal harm when administered to a pregnant woman . There are no available data on erdafitinib 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 . Advise pregnant women and females of reproductive potential of the potential risk to the fetus .
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 erdafitinib and for one month following the last dose .
Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with erdafitinib .
Balversa can cause fetal harm when administered to a pregnant woman . Advise females of reproductive potential to use effective contraception during treatment with erdafitinib and for one month after the last dose .
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with erdafitinib and for one month after the last dose .
Based on findings from animal studies, erdafitinib may impair fertility in females of reproductive potential .
Safety and effectiveness of erdafitinib in pediatric patients have not been established .
No overall differences in safety or effectiveness were observed between these patients and younger patients in the use of erdafitinib .
Balversa plasma concentrations were predicted to be higher in patients with the CYP2C93/3 genotype . Monitor for increased adverse reactions in patients who are known or suspected to have CYP2C93/3 genotype .
Carcinogenicity studies have not been conducted with erdafitinib .
Balversa 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 .
Food Interaction
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of erdafitinib.
- Exercise caution with St. John's Wort. This herb induces the CYP3A metabolism of erdafitinib and may reduce its serum concentration.
- Take with or without food.
Balversa Drug Interaction
Major: cholecalciferolModerate: acetaminophen / oxycodone, rifaximinUnknown: aspirin, fluticasone, escitalopram, metoprolol, esomeprazole, albuterol, bifidobacterium infantis / lactobacillus acidophilus, ocular lubricant ophthalmic, acetaminophen, cyanocobalamin, saliva substitutes topical
Balversa Disease Interaction
Moderate: hyperphosphatemia, ocular disorders, severe hepatic/renal
Volume of Distribution
The mean apparent volume of distribution determined for erdafitinib is about 26 to 29 L in patients .
Elimination Route
Following administration of erdafitinib 8 mg once daily, the mean (coefficient of variation [CV%]) steady-state maximum observed plasma concentration (Cmax), area under the curve (AUCtau), and minimum observed 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, erdafitinib exposure (maximum observed plasma concentration [Cmax] and area under the plasma concentration time curve [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 and the mean accumulation ratio was 4-fold .
The median time to achieve peak plasma concentration (tmax) was 2.5 hours (range: 2 to 6 hours) . And finally, no clinically meaningful differences with erdafitinib pharmacokinetics were observed following administration of 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) in healthy subjects .
Half Life
The mean effective half-life documented for erdafitinib is 59 hours , although it has also been observed between 50 to 60 hours .
Clearance
The mean total apparent clearance (CL/F) documented for erdafitinib is about 0.362 L/h , while the oral clearance has been observed to be approximately 0.26 L/h .
Elimination Route
After administering a single oral dose of radiolabeled erdafitinib, about 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged) .
Innovators Monograph
You find simplified version here Balversa
