On Dec. 7, 2022, the U.S. Food and Drug Administration (FDA) approved Vivimusta (bendamustine – Slayback Pharma) injection solution, 100mg/4mL. An alkylating agent, it is given by IV infusions for treating adults who have chronic lymphocytic leukemia (CLL) or indolent B-cell non-Hodgkin lymphoma (NHL) that advanced during treatment with rituximab or within six months after rituximab treatments stopped. For CLL, the recommended dose is 100mg/m2 on each of the first two days for up to six 28-day cycles. The dose for NHL is 120mg/m2 given on each of the first two days of 21-day cycles with an upper limit of eight cycles. Two other bendamustine solutions, Belrapzo® (Eagle Pharmaceuticals) and Bendeka® (Teva/Cephalon) also are available in the United States. Both of them and Vivimusta were approved under section 505(b)(2) of the Food, Drug, and Cosmetic Act (FDCA), which allows the submitting company to use documentation from a similar product that already is FDA approved rather than requiring a repeat of the clinical trials. For all three products, the originator was Treanda® (Teva), which now is manufactured only as a powder for reconstitution; its solution version has been discontinued. They are not generics and they are not interchangeable with each other or any other bendamustine product. Several other bendamustine products have FDA approval, but no others have been released to the U.S. market. Launch, distribution, and pricing information for Vivimusta are not yet available. Prescribing information for Vivimusta is here.
Olpruva Receives FDA Approval
A new dosage form of sodium phenylbutyrate, Olpruva™ (Acer Therapeutics) for oral suspension was approved by the FDA on Dec. 22, 2022. It is a nitrogen-binding agent indicated to treat patients who have a urea cycle disorder (UCD). Patients who have a UCD, a group of hereditary conditions that are caused by missing or deficient enzymes, cannot clear nitrogen from their bodies. The resulting accumulation of ammonia damages the brain and other organs. In the U.S., only about one in 8,500 babies who are alive at birth – approximately 425 infants annually – are diagnosed with a UCD. Mild cases may not be evident until later in life. Among the more common UCDs are deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), and argininosuccinic acid synthetase (AS). Along with standard care that includes dietary restrictions on protein, Olpruva is approved for patients who weigh at least 20kg (44 pounds) and who have a body surface area (BSA) of at least 1.2m2. The recommended daily dose range is 9.9gm/m2 to 13gm/m2, depending on the patient’s blood levels of ammonia, to an upper limit of 20gm/day. For use, Olpruva is divided into three to six daily doses. Each dose is dissolved in four ounces of water and consumed orally with food. It should not be given through a gastrostomy or nasogastric (NG) tube. Nervous system damage it may cause can result in confusion, fatigue, headaches, nausea, and sleep disturbances. Other side effects may include reduced blood potassium levels and increased swelling. In the U.S., sodium phenylbutyrate already is dispensed in bottles of oral granules (Pheburane® Oral Pellets), bottles of powder for oral solution (Buphenyl® and generics), and oral tablets (Buphenyl® and generics). Olpruva is the first to be packaged in premeasured individual portions, in six strengths from 2gm to 6.67gm per packet, which can be transported easily. Olpruva’s prescribing information is here.
New Imaging Agent Approved to Assess Lung Function
Polarean Imaging’s Xenoview™ (xenon Xe 129 hyperpolarized) was approved by the FDA for oral inhalation on Dec. 23, 2022. To be used with magnetic resonance imaging (MRI), it is a unique drug-device combination product that measures lung function for patients as young as 12 years old who are being considered for procedures such as lung transplants. Using patented equipment at the imaging facility, inert xenon gas is hyperpolarized to magnetically align its atomic nuclei, mixed with other gasses, and packaged in a 1,00mL proprietary Dose Delivery Bag that contains no less than 75mL of hyperpolarized xenon Xe 129. Immediately before the MRI procedure, the patient inhales the entire bag of Xenoview, the amount of xenon Xe 129 is confirmed and the patient holds his breath during the MRI scan – about 10 to 15 seconds. A device, the Xenoview 3.0T Chest Coil transmitter/receiver, and Xenoview VDP software was FDA approved at the same time. No launch plans or cost information have been announced. Check here for prescribing information.
FDA Approves NexoBrid
NexoBrid® (anacaulase-bcdb – MediWound) for topical gel, 8.8%, was FDA approved on Dec. 28, 2022. A blend of enzymes that break down proteins, it is indicated for removing eschar (dead tissue) for adults who have partial- and/or full-thickness burns caused by heat or fire. In clinical studies, using it allowed for earlier eschar removal and less need for surgery. It is dispensed as a powder that is combined with a co-packaged gel, to make either 20gm or 50gm of active product. Before using NexoBrid, burns should be cleaned, a topical antibiotic solution should be in contact with the burns for two hours or more and a thick layer of ointment should be applied around the burned area to protect unburned skin. A healthcare professional mixes and applies NexoBrid to the affected areas, which are then covered with occlusive bandages for four hours until the gel is removed. No more than 15% of the patient’s total body surface area (BSA) should be treated. If needed, a second dose may be applied after 24 hours, but the total treated BSA should be 20% or less. NexoBrid should not be used on the face or mucous membranes of the groin area. Because it is derived from specific plants and fruits, NexoBrid should not be used for patients who are allergic to bromelains, papaya, papain, or pineapple. In the U.S., it will be distributed by Vericel Corp. starting in the second quarter of 2023. Here is the full prescribing information.
Pediatric Indication for Wegovy
The indication for Wegovy® (semaglutide – Novo Nordisk) injection, 2.4mg, was broadened by the FDA on Dec. 23, 2022, to treat obesity for patients as young as 12 years old. Along with diet and exercise, it originally was approved for adults in 2021. Pediatric patients eligible for its use must be in the 95th or higher percentile of body mass index (BMI) for their age and gender. For patients of all ages, dosing starts at 0.25mg once each week for four weeks, then increases to 0.5mg/week for four weeks, 1mg/week for four weeks, and 1.7mg for four weeks. The maintenance dose of 2.4mg/week begins at the beginning of the 17th week. Wegovy is packaged in cartons of four prefilled, single-dose syringes in each of the five strengths. It is delivered as subcutaneous (SC) injections into the abdomen, thigh, or upper arm. A glucagon-like peptide-1 (GLP-1) receptor agonist, Wegovy contains the same active ingredient as Ozempic® SC injection, which is used weekly at a lower dose to manage type 2 diabetes and to lessen the chance of cardiovascular (CV) events for adult patients who have both diabetes and CV disease. A daily oral version, Rybelsus® tablets, treats adults who have diabetes, only. As with all GLP-1 agonists, the labeling for Wegovy contains a boxed warning about tumors of the thyroid gland (thyroid C-cell tumors) that have occurred among laboratory rodents treated with some GLP-1 receptor agonists in preclinical studies. However, whether Wegovy causes humans to develop thyroid C-cell tumors, such as medullary thyroid carcinoma (MTC), is not yet known. Patients who have MTC, individuals with close family members who have thyroid C-cell tumors, and patients who have Multiple Endocrine Neoplasia syndrome type2 (tumors in more than one gland) should not use Wegovy. Look here for its revised prescribing information.
Accord Healthcare recalled one lot of daptomycin injections to the consumer level on Dec. 23, 2022. The same lot number (R2200232) and expiration date (January 2025) were used for two strengths of the drug. Some 500mg vials incorrectly were shipped in cartons marked as 350mg. Although the possibility of severe adverse effects is very low, higher than prescribed doses of daptomycin could intensify side effects such as injection reactions and increased creatine phosphokinase (CPK) levels, potentially leading to hemodialysis. Daptomycin is an antibiotic used to treat complicated skin and skin structure infections caused by certain bacteria. The FDA notice has additional information.