Balversa Receives Full FDA Approval
When Balversa™ (erdafitinib) tablets were granted Accelerated Approval by the U.S. Food and Drug Administration (FDA) in April 2019, its manufacturer, Janssen, was required to conduct a clinical trial to validate its effectiveness. The positive results from that study prompted the FDA to give Balversa full approval on Jan. 19, 2024. It is a first-in-class kinase inhibitor that blocks fibroblast growth factor receptors (FGFR), which can prolong cancer cell’s survival and promote their growth. It is fully approved to treat adults who have locally advanced or metastatic urothelial (bladder) carcinoma that has FGFR3 mutations and that has worsened despite one or more rounds of treatment. Patients who have mutations in FGFR2 are no longer included in the approval. In the study, patients using Balversa averaged a 36% less chance of dying than patients given standard chemotherapy (chemo). The overall survival (OS) rate for actively treated individuals averaged 12.1 months as opposed to 7.8 months for those receiving chemo. Originally, taking Balversa was restricted to patients who previously had been treated with platinum-based combination chemotherapy (chemo). Now, it can be used second line after therapy with chemo or any other drugs. It should not be used for individuals who are candidates for, but who have not been treated with, a programmed death receptor (PD-1) blocker, such as Keytruda® (pembrolizumab), or a programmed death-ligand 1 (PD-L1) inhibitor, such as Tecentriq® (atezolizumab). The recommended starting dose for Balversa is 8mg (two 4mg tablets) orally once a day, increasing to 9mg (three 3mg tablets) daily if blood phosphate levels stay within acceptable limits and no major side effects occur after the first two to three weeks of treatment. Complete prescribing information is here.
Expanded Indication for Zynrelef
The indications for Zynrelef® (bupivacaine/meloxicam – Heron Therapeutics) extended-release solution were widened by the FDA on Jan. 23, 2024. The combination of a long-acting, extended-release local anesthetic and a non-steroidal anti-inflammatory drug (NSAID) now is indicated to manage pain for adults who have undergone a bigger range of surgical procedures. Originally approved in May 2021, it was indicated then to relieve pain for up to 72 hours following surgery to remove bunions, repair inguinal hernias, or replace knee joints. Later in 2021, it gained additional approvals to be used after foot and ankle operations, small-to-medium open abdominal procedures, and lower extremity total joint arthroplasties. It now also can be used for foot, ankle, and other soft tissue and orthopedic operations that do not involve direct exposure of joint cartilage. Zynrelef is a one-time treatment that is instilled (introduced into the site of the procedure without using a needle) by the surgical team into the soft tissue around a surgical site or joint before the incision is closed. Four strengths are available in single-dose vials. No other local anesthetics should be used within four days of instilling Zynrelef. It is not indicated for children or for use after other types of surgery. Like all NSAIDs, Zynrelef has boxed warnings about possibly life-threatening blood clots and gastrointestinal (GI) side effects that may be associated with its use. Here is the updated prescribing information.
New Pediatric Indication for Dupixent
On Jan. 25, 2024, the FDA broadened the eosinophilic esophagitis (EoE) indication for Regeneron and Sanofi’s Dupixent® (dupilumab) injection to include children who are as young as one year old and who weigh at least 15kg (33 pounds). Given subcutaneous (SC) injections, it is the first drug to be FDA-indicated for treating young children who have EoE, a progressive inflammatory disease. For EoE, the recommended doses are once every two weeks at 200mg for those who weigh between 15kg and 30kg (66 pounds) and at 300mg for patients between 30kg and 40kg (88 pounds). For patients who weigh 40kg or more, the dose becomes 300mg once every week. The manufacturers estimate that around 21,000 patients younger than 12 years old presently are under treatment for EoE using other drugs off-label. Nearly all pediatric patients who have EoE also have other inflammatory conditions, such as atopic dermatitis and asthma. In the EoE KIDS clinical trial, 66% of patients who used Dupixent reached histological remission at four months as compared to 3% of children given a placebo. About one-half of the participants, including those who switched to active treatment from placebo, remained in remission for one year or longer. Dupixent is available in single-dose 200mg and 300mg pens as well as in 100mg, 200mg, and 300mg prefilled syringes. A parent or other caregiver should administer doses for children under the age of 12 years, but older children may be able to self-inject after being trained. In addition to the treatment of EoE, Dupixent is approved by the FDA to treat adults who have prurigo nodularis or chronic rhinosinusitis with nasal polyposis, patients aged six years and older for asthma with an eosinophilic phenotype and patients aged six months and older for atopic dermatitis. Click here to see its revised prescribing information.
MedWatch Updates
CAR-T Therapies
Following up on a Safety Communication that it released in November 2023, the FDA now is requiring the manufacturers of chimeric antigen receptor (CAR)-T cell treatments to include a new boxed warning on the label. Products that are approved for use in the United States now must include information in their labeling materials about the possibility that using any of the therapies may increase the risk of developing a second cancer. Two of the drugs – Abecma® (idecabtagene vicleucel) and Carvykti® (ciltacabtagene autoleucel) are directed at B-cell maturation antigen (BCMA); and four others – Breyanzi® (lisocabtagene maraleucel), Kymriah® (tisagenlecleucel), Tecartus® (brexucabtagene autoleucel), and Yescarta® (axicabtagene ciloleucel) target cluster of differentiation (CD)19. BCMA and CD19 are associated with B-cell cancers. The drugs are tailored to each patient by collecting and then altering some of the patient’s T cells so that they bind specifically to BCMA or CD19. When the modified CAR-T cells are infused back into the patient, they inactivate the target protein, destroying the cancer cells that produce it. A small number of patients who received CAR-T therapy have developed T-cell malignancies – some that can be linked to the therapy — and some patients have died. All six drugs are dispensed under risk evaluation and mitigation strategies (REMS) and all already have boxed warnings about cytokine release syndrome (CRS), neurologic problems, and other adverse effects that may be associated with their use. Some have other boxed warnings, as well. For more information about each drug, check the FDA’s notification letters here.
Prolia
Prescribing information for Prolia® (denosumab – Amgen) injection also will now carry a boxed warning. The drug, given SC twice a year to treat osteoporosis, has been found to raise the risk of dangerous hypocalcemia (low levels of calcium in the blood) for patients who have chronic kidney disease (CKD). Patients who need dialysis are thought to be at the highest risk, as some patients have had to be hospitalized and some have died. Patients who have CKD and use Prolia should notify their healthcare providers right away if they experience new or worsening symptoms such as difficulty breathing, heart rhythm changes, muscle cramps, numbness, seizures or vomiting. Health professionals are advised to watch calcium blood levels carefully for patients using both Prolia and dialysis and to ensure that patients take supplements for calcium and vitamin D to maintain adequate blood calcium levels. Updated prescribing information is here. More information from the FDA is here.