Expanded Indication for Abecma
The indication for Abecma® (idecabtagene vicleucel – Bristol Myers Squibb), a B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR) T-cell therapy was broadened by the FDA on April 4, 2024. It originally was FDA-approved in March 2021 to treat adult patients who have relapsed or refractory (r/r) multiple myeloma and who already have had four or more rounds of treatment with drugs that include an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Now, it is indicated after at least two prior lines of therapy comprising one or more drugs from each of the same drug classes. It works by inactivating BCMA, which is heavily expressed in multiple myeloma cells. After T-cells are extracted from the patient’s blood, they are genetically modified and then duplicated to very high amounts in a laboratory. Before its use, conditioning chemotherapy (chemo) is administered for three days to prepare the patient’s bone marrow to receive Abecma. Two days later, a cell suspension of 300×106 to 510×106 CAR-positive T cells is given as a single intravenous (IV) infusion under sterile conditions in certified healthcare facilities and by specially trained providers. Patients should be observed for seven days and they should stay close enough to reach the facility quickly for four weeks or longer after the procedure. Abecma, which is available only under a risk evaluation and mitigation strategy (REMS), has boxed warnings that using it may be associated with severe side effects that include hemophagocytic lymphohistiocytosis/macrophage activation syndrome, (HLH/MAS), cytokine release syndrome (CRS), neurologic toxicities, prolonged cytopenia, and a risk of developing other T-cell malignancies. The wholesale acquisition cost for Abecma, alone, is around $498,410. Here is its updated prescribing information.
Carvykti Indication Extended
Johnson & Johnson’s Carvykti® (ciltacabtagene autoleucel) also received the FDA’s approval for a wider indication on April 5, 2024. It was approved to treat adult patients who have r/r multiple myeloma, who have undergone at least one prior line of therapy including with a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide. Initially, it was approved in February 2022, for treating r/r multiple myeloma following four or more lines of therapy that included an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. An autologous CAR T-cell therapy that targets BCMA, Carvykti uses a patient’s T-cells which are harvested in a designated medical center that has specially trained health professionals and appropriate equipment to perform the procedures and to manage any side effects that may occur. The cells are then sent to a manufacturing center where they are modified and cultured to increase the number of active cells. After three days of pretreatment with chemo, a cell suspension of Carvykti with a target dose ranging between at least 0.5×106 and an upper limit of 1.0×106 viable CAR-positive T-cells/kg is administered by IV infusion. When they are returned to the patient, the T-cells kill the BCMA-expressing cancer cells. Patients must be seen in the health center for a minimum of 10 days after treatment and they should remain close to the center for a minimum of 28 days. A boxed warning advises that using Carvykti can result in potentially severe side effects such as HLH/MAS, Parkinsonism, immune effector cell-associated neurotoxicity syndrome (ICANS), (Guillain-Barré syndrome, persistent cytopenia, CRS or secondary blood cancers. It is dispensed and administered only under a REMS. By itself, the WAC for Carvykti is approximately $478,950. Its current prescribing information may be found here.
New Enhertu Indication
As a Breakthrough Therapy and under Priority Review, Enhertu® (fam-trastuzumab-deruxtecan-nxki – AstraZeneca/Daiichi Sankyo) injection gained a new Accelerated Approval from the FDA on April 5, 2024. The FDA also used Project Orbis and Real-Time Oncology Review to expedite its review. Enhertu is newly indicated as a treatment for adults who have previously treated solid tumors, designated as immunohistochemistry 3 (IHC3+). For patients to be considered, the cancer must test positive for human epidermal growth factor receptor 2 (HER-2), it cannot be removed by surgery or it has metastasized and the patient has no other treatment options. Enhertu is both the first antibody-drug conjugate and the first drug targeted to HER-2 to be FDA-approved for tumors no matter what body parts they affect. Trastuzumab is an antibody that binds to HER2 proteins in the cancer cells, which the attached topoisomerase I inhibitor, deruxtecan, causes to disintegrate. In the open-label, phase II DESTINY-PanTumor02 clinical study, it was successful in treating bladder, colorectal, lung, pancreatic, reproductive tract, and other cancers. In the results from the study, 37.1% of trial patients using Enhertu had some response to it, which lasted an average of 11.3 months with progression-free survival (PFS) averaging 6.9 months. A boxed warning and a Medication Guide for patients caution that using Enhertu may cause lung conditions, including interstitial lung disease (ILD), which is progressive scarring of lung tissue that could be fatal. It also may damage a developing baby, so women of childbearing age should use effective forms of contraception while being treated with Enhertu. More than one in four patients in the trial had a Grade 3 or higher side effect, including 10.8% who developed ILD. The recommended dose of Enhertu for treating solid tumors is 5.4mg/kg as an IV infusion once every three weeks. Confirmatory results from additional clinical trials will be needed to finalize Enhertu’s full approval for treating solid tumors. It has prior indications for treating adults who have advanced cases of three other HER-2+ cancers — breast cancer (including those that express small amounts of HER-2), gastric/gastroesophageal junction (GEJ) adenocarcinoma and non-small cell lung cancer (NSCLC). Check here for its complete prescribing information.
Age Range Extended for Dovato
The FDA has added younger patients to the indication for Dovato (dolutegravir, 50mg/lamivudine, 300mg – ViiV Healthcare) tablets. On April 5, 2024, the indication was expanded to treat HIV-1 for patients as young as 12 years old who weigh at least 25kg (55 pounds). The fixed-dose, once-daily tablet combines an integrase strand transfer inhibitor (INSTI) and a nucleoside analog reverse transcriptase inhibitor (NRTI). Patients new to drug therapy for HIV-1 can be started on Dovato and patients currently treated with a different regimen can be switched to it provided that they are stabilized on their present drugs, that they have not failed previous drug therapy for HIV-1 and that they have no substitutions that may resist either of the drugs in Dovato. It should not be taken at the same time that the patient is using dofetilide, which treats arrhythmia. Due to its lamivudine content, Dovato has a boxed warning that the hepatitis B virus (HBV) may become resistant to lamivudine if it is used for patients who have HBV in addition to HIV-1. If treatment stops, latent HBV may reactivate, as well. Women of reproductive age should be tested to rule out pregnancy before starting treatment because dolutegravir may cause nerve defects in a developing fetus – particularly early in pregnancy. For Dovato’s revised prescribing information, go here.
Wider Pediatric Indication and New Strength for Fasenra
AstraZeneca was approved by the FDA on April 5, 2024, to extend the use of Fasenra® (benralizumab) to children between the ages of six years old and 11 years old. Used along with other asthma drugs, it reduces severe asthma attacks for patients who have asthma that has an eosinophilic phenotype. Administered by subcutaneous (SC) injections, it blocks interleukin-5 (IL-5) receptors on eosinophils, white blood cells that contribute to increased sensitivity of the airways among affected patients. According to the Allergy and Asthma Network, about 10% of school-aged children in the U.S. have asthma with approximately 5% of all asthma patients having an eosinophilic phenotype. Following three monthly doses, Fasenra is used once every two months. For pediatric patients younger than 12 years old, the recommended doses are 10mg for children weighing less than 35kg (77 pounds) and 30mg (the same dose as adults) for those who are heavier. To accommodate the lower dose, a new 10mg prefilled syringe is being introduced. The higher dose is available in both prefilled syringes and single-dose autoinjector pen devices. All 10mg doses for children under 12 years old and all doses administered by prefilled syringes should be given by a healthcare professional, but caregivers may be trained to give children the 30mg doses through an autoinjector. Fasenra is not meant to treat acute episodes of asthma or acute bronchospasm. Here is its updated prescribing information.
New Xcopri Route of Administration
A drug that treats adults who have partial-onset seizures, Xcopri® (cenobamate – SK Life Science) tablets, was FDA-approved for a new method of administration on April 5, 2024. The tablets, which range in strength from 12.5mg to 200mg, now can be crushed and mixed into 25mL (about five teaspoons) of water to drink or be given through an oral syringe into a nasogastric (NG) tube for patients who have trouble swallowing whole tablets. The mixture should be well blended by swirling the contents and used right away. The cup or syringe then should be refilled with 25mL or 10mL (two teaspoons) of water, respectively; and given again to assure that no particles of the drug were missed. A C-V-controlled substance, Xcopri blocks voltage-gated sodium currents and modulates gamma-aminobutyric acid (GABA) channels to interrupt nerve impulses and decrease the risk of seizures. Patients start on 12.5mg once a day and then gradually increase to a maintenance dose of 200mg once daily. Some patients may need the maximum recommended dose of 400mg/day. Xcopri can be used alone or in combination with other antiepileptic drugs. Dosages may need to be modified, however, when antiepileptics from different classes are taken at the same time. If it is discontinued, doses of Xcopri should be lowered gradually over two weeks or longer. Prescribing information is here.