Vraylar Receives New Indication
AbbVie’s atypical antipsychotic, Vraylar® (cariprazine) capsules was awarded another U.S. Food and Drug Administration (FDA) indication on Dec. 16, 2022, for treating adults who have a major depressive disorder (MDD). It will be combined with antidepressant therapy to treat MDD that does not resolve adequately with an antidepressant alone. In ways that are different from antidepressants, Vraylar acts on the neurotransmitter receptors for dopamine and serotonin to help normalize their levels. For MDD, recommended daily dosing of Vraylar begins at 1.5mg, which can be increased, if needed, to 3mg after two weeks. Vraylar also is FDA-approved to treat schizophrenia and all phases (depressive, manic, and mixed) of bipolar I disorder. All atypical antipsychotics carry a boxed warning against using them for elderly or pediatric, adolescent, and young adult patients. They may increase the risk of death for older patients and promote suicidal feelings or actions for young patients. In clinical trials, Vraylar’s most common side effects included insomnia, nausea, and restlessness. Here is its updated prescribing information.
New Indication for Pemfexy with Keytruda
The FDA awarded a new indication to Pemfexy® (pemetrexed – Eagle Pharmaceuticals) solution for injection on Dec. 16, 2022. Pemfexy now can be used, along with Keytruda® (pembrolizumab) and platinum-based chemotherapy (chemo), as front-line treatment of non-squamous, non-small cell lung cancer (NSCLC) that has metastasized, but that does not have mutations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes. For the new indication, it will be given after Keytruda and before chemo as a 10-minute, 500mg/m2 intravenous (IV) injection on the first day of each 21-day treatment cycle. Because it is a folate analog metabolic inhibitor, patients receiving Pemfexy need supplementation with oral doses of folic acid every day and intramuscular (IM) injections of vitamin B12 once every three cycles. Using it also may interfere with the activity of bone marrow, increasing the risk of blood abnormalities and serious infections for patients. Pemfexy also may cause kidney damage, severe skin conditions, scarred lung tissue, and harm to an unborn baby. Under the terms of a settlement agreement, Eagle introduced Pemfexy, a branded alternative for Alimta® (pemetrexed – Eli Lilly) powder for solution for injection, in the U.S. during the first quarter of 2022. It has additional indications, either alone or in combination with other cancer drugs, to treat other types of non-squamous NSCLC and certain malignant pleural mesotheliomas. The labeling for Keytruda, which has indications for numerous types of cancer treatment, has been updated to include the new approval with Pemfexy and chemo, as well. Check here for Pemfexy’s complete prescribing information.
Three Full Approvals for Keytruda
Additionally, on Dec. 16, 2022, the FDA changed into full approval an alternate dosing regimen for Keytruda that previously had been granted only Accelerated Approvals. Based on interim results from mid-stage clinical trials, Accelerated Approvals are conditional upon support for their effectiveness and safety from supplementary studies. Results from the KEYSTONE-555 trial of Keytruda’s bioavailability convinced the FDA to finalize three of four Accelerated Approvals from 2020. Now fully approved are doses of 400mg once every six weeks for treating adults who have cutaneous squamous cell carcinoma, unresectable or metastatic solid tumors that have high mutational burdens, and a large group of other cancers. Keytruda’s original full approval for all three indications is 200mg once every three weeks. The longer dosing intervals are more convenient and trial data show they are as effective and safe as the smaller doses that are given more often. Full approval for the same dosing schedule to treat classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma is still under review. A complete list of Keytruda’s indications is in prescribing information here.
The FDA Gives Tymlos a New Indication
On Dec. 19, 2022, the FDA approved a new indication for Radius Health’s parathyroid hormone-related peptide [PTHrP (1-34)] analog, Tymlos® (abaloparatide) injection, which promotes the formation of bone. Originally approved in 2017 to treat postmenopausal women who have osteoporosis and who also have a high risk of fracture, it now is indicated to increase bone mineral density (BMD) for men who have the same risk factors. It also can be used by patients who have not had success with other treatments for osteoporosis. Although women are more likely to have a bone fracture related to osteoporosis, about one-quarter of men who are older than 50 years old also will have an osteoporosis-associated fracture. In a clinical trial of 228 men, spinal BMD among those who received Tymlos for 12 months increased by an average of 8.5% as compared to a 1.2% increase for patients given a placebo. The recommended dose is one 80mcg injection given subcutaneously (SC) into the upper abdomen once every day. Tymlos is packaged in prefilled pen injector devices that each hold 30 doses. Some patients using it may experience orthostatic hypotension (low blood pressure when standing up), which has symptoms such as dizziness, fast heartbeats, and/or nausea. For at least the first few injections, the patient should be in a place where sitting or lying down is possible if symptoms occur. Forteo® (teriparatide – Eli Lilly), the only other PTH analogue on the U.S. market for treating osteoporosis, has similar indications, dosing recommendations, and warnings. Continued use of either drug beyond a cumulative total of two years is not recommended. Here is the revised prescribing for Tymlos.
Full COVID-19 Indication for Actemra
Genentech, a member company of the Roche Group, gained full FDA approval for a COVID-19 indication on Dec. 21, 2022. The IV form of monoclonal antibody interleukin-6 (IL-6) receptor inhibitor, Actemra® (tocilizumab) injection was approved to treat adults who are in the hospital as a result of COVID-19 and who need systemic corticosteroids and either supplemental oxygen, mechanical ventilation or extracorporeal membrane oxygenation (ECMO). It qualified for an emergency use authorization (EUA) from the FDA in June 2021 as a treatment for patients as young as two years old who need the same levels of hospital care for COVID-19. The EUA continues to be in effect for patients under the age of 18 years old. Actemra is administered as one dose of 8mg/kg for patients who weigh 30 kg (66 pounds) or more and 12mg/kg for those who weigh less in an IV infusion that lasts one hour. With an SC dosage form that is not interchangeable with the IV formulation, Actemra has previous adult and pediatric indications to treat several inflammatory conditions. They include rheumatoid arthritis (RA), giant cell arteritis, juvenile idiopathic arthritis (JIA), and systemic sclerosis-associated interstitial lung disease (SSc-ILD). The IV version also is used to treat cytokine release syndrome, a possible side effect of chimeric antigen receptor (CAR-T) therapy. A boxed warning cautions that using Actemra may predispose patients to opportunistic bacterial, fungal, viral, or other infections. Before Actemra is used and during treatment with it, patients should be tested for tuberculosis (TB). Here is Actemra’s updated prescribing information; here is its current prescriber’s EUA Fact Sheet and here is its revised patient and caregiver’s Fact Sheet.
Imaging Agent, Cytalux, Gets New Indication
Cytalux® (pafolacianine) injection received a new indication from the FDA on Dec. 16, 2022. It now is indicated to highlight both malignant and noncancerous lesions in the lungs while adult patients are undergoing surgery for lung cancer. Made by On Target Laboratories, Cytalux was first approved by the FDA in November 2021 for locating malignant ovarian tissue during surgical procedures to remove it. Containing a near-infrared dye and a targeting molecule, it attaches to folate receptors, which are overproduced by ovarian cancer cells and possibly by lung cancers, as well. Administered in a one-hour IV infusion at a dose of 0.025mg/kg, it is given between one hour and 24 hours before surgery for lung cancer. In the open-label ELUCIDATE clinical trial, treatment with Cytalux revealed cancers that had not been found by traditional visual or manual examinations for 24% of the 110 patients. An imaging system also is FDA approved specifically to use with it. For its full prescribing information, look here.