New Brukinsa Indication

BeiGene’s Brukinsa^® (zanubrutinib) capsules were granted a new indication by the U.S. Food and Drug Administration (FDA) on March 7, 2024. Under the FDA’s Accelerated Approval and Fast-Track programs, Bruton’s tyrosine kinase (BTK) inhibitor was approved as a third-line or later therapy to treat adults who have relapsed or refractory follicular lymphoma (r/rFL). It will be used in combination with Gazyva^® (obinutuzumab – Genentech) injection. A slowly progressing form of non-Hodgkin lymphoma (NHL), FL affects about 15,000 new patients, mostly older adults, in the U.S. each year. Relatively easy to treat initially, FL frequently develops resistance to treatment and patients often relapse. In the phase II ROSEWOOD clinical trial, the overall response rate (ORR) to treatment with Brukinsa and Gazyva was 23% higher than with Gazyva by itself (69% versus 46%, respectively). Available in the U.S. since 2019, Brukinsa has full FDA approvals to treat Waldenström’s macroglobulinemia (WM), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL). It has additional Accelerated Approvals for mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). For all of its indications, the recommended daily dose is 320mg (two capsules) – either all at once or divided into two equal doses. Brukinsa has Orphan Drug status for treating several types of cancer, including FL. Numerous other drugs — including chimeric antigen receptor (CAR-T) therapies – also are FDA-approved to treat r/rFL. Since Burkinsa’s Accelerated Approval for r/rFL is based on results from a mid-stage clinical study, additional positive results to confirm its benefits will be needed before full FDA approval is granted. Check here for its complete prescribing information.

Breyanzi Gets New Indication

On March 14, 2024, Bristol Myers Squibb announced that Breyanzi^® (lisocabtagene maraleucel) suspension has become the first CAR-T cell therapy to gain the FDA’s Accelerated Approval for treating adults who have relapsed or refractory chronic lymphocytic leukemia (r/rCLL) or small lymphocytic lymphoma (r/rSLL). Further documentation of its effectiveness and safety for treating r/rCLL and r/rSLL will be needed for full FDA approval. Also called Liso-cel, it will be used as a third-line or later treatment following therapy with at least one BTK inhibitor and one B-cell lymphoma 2 (BCL-2) inhibitor. Breyanzi targets the CD19 antigen expressed by many B-cell malignancies. Doses are tailored to each patient using their own genetically modified T-cells, which are white blood cells that have been engineered to attack cancer cells once infused back into the patient. It is administered as one intravenous (IV) infusion. Initially FDA-approved in February 2021, it also treats adults who have relapsed or refractory diffuse large B-cell lymphomas (r/rDLBCL) that have not responded to one or two other types of systemic treatment. Its label carries a boxed warning due to potentially life-threatening cytokine release syndrome (CRS), neurological events, and T-cell cancers that may be related to its use. Breyanzi is available only through hospitals and associated outpatient clinics that are certified through the Breyanzi Risk Evaluation and Mitigation Strategy (REMS) program. A BTK inhibitor, Eli Lilly and Company’s Jaypirca^® (pirtobrutinib) tablets was granted Accelerated Approval from the FDA on Dec. 1, 2023, for the same two indications. In a clinical study, 72% of patients treated with Jaypirca responded partially to it, with the average length of response at 12.2 months. In a separate trial for Breyanzi, responses were partial for 25% of treated patients and complete for 20%. Responses for Breyanzi averaged 35.3 months. Breyanzi’s wholesale acquisition cost (WAC) is roughly $450,000. Current prescribing information may be found here.

New Indication for Livmarli

Livmarli^® (maralixibat – Mirum Pharmaceuticals) oral solution was approved for a second indication by the FDA on March 13, 2024. Originally FDA-approved in September 2021, it treats cholestatic pruritus caused by Alagille syndrome (ALGS) for children as young as three months old. The ileal bile acid transporter (IBAT) inhibitor now also is indicated to treat patients at least five years old who have progressive familial intrahepatic cholestasis (PFIC). A rare hereditary condition, PFIC is believed to affect about one of every 50,000 to 100,000 babies born in the U.S. each year. It results from the accumulation of bile in the blood because the liver does not process bile normally. One key symptom is extreme itching of the skin. Very little of Livmarli is absorbed from the intestines, where it blocks the reabsorption of bile acids, forcing more to be excreted and leaving less to recirculate and alleviating itch. The recommended dose for PFIC begins at 285mcg/kg once a day, then increases to 285mcg/kg twice a day, to 428mcg/kg twice a day, and, finally, to 570mcg/kg twice a day with a maximum daily dose of no more than 38mg. Doses should be taken one-half hour or more before the patient eats the first food of the day. Here is the revised prescribing information.

Pediatric Indication Approved for Praluent

The indication for Praluent^® (alirocumab – Regeneron Pharmaceuticals) injection to treat heterozygous familial hypercholesterolemia (HeFH) now is extended to patients as young as eight years old. The FDA made the decision on March 8, 2024. Praluent is used along with a modified diet and other drugs for reducing high cholesterol. By inhibiting a protein known as proprotein convertase subtilisin kexin type 9 (PCSK9), it increases the number of low-density lipoprotein cholesterol (LDL-C) receptors and speeds up the elimination of LDL-C from the blood. HeFH is a fairly common inherited disorder thought to affect about one American in 250. For patients who have it, genetic mutations cause cholesterol to be retained, often beginning at a very young age. Blood levels of LDL-C often remain elevated despite diet, exercise, and aggressive drug treatment. Patients who have HeFH may not have symptoms, but they are likely to have relatives who have developed heart disease in childhood or early adulthood. Typically, Praluent is given once every four weeks as a subcutaneous (SC) injection through a single-dose prefilled syringe or auto-injector. For patients under the age of 18 years old, doses are based on weight. For those who weigh less than 50kg (110 pounds), the dose is 150mg; for pediatric patients weighing 50kg or more, the dose is 300mg (given as two concurrent 150mg injections at different sites on the body). On the U.S. market since 2015, Praluent also has indications to treat adults who have primary hyperlipidemia, to lower LDL-C for adults who have homozygous familial hypercholesterolemia (HoFH), and to decrease the need for hospitalizations due to cardiovascular (CV) events, such as heart attacks and strokes, in adults who have CV disease. For revised prescribing information, go here.

New Recommendations for Storing Asceniv and Bivigam 

Changes to the storage conditions for ADMA Biologics’ IV immunoglobulin (IVIG) products, Asceniv^™ (immune globulin intravenous, human – slra 10% liquid) and Bivigam^® (immune globulin intravenous, human – 10% liquid), were FDA approved on March 1, 2024. Originally, they had to be refrigerated constantly. Since December 2022, however, both products have been approved to be kept at room temperature (77˚Fahrenheit or lower) for up to a total of one month during the first 24 months of the product’s 36-month-long shelf life. Now, they can be held at room temperature for no longer than one month at any period until their labeled expiration dates. They each are given by IV infusion to treat primary humoral immunodeficiencies (PIs) – Asceniv for patients as young as 12 years old, and Bivigam for patients who are at least two years old. The manufacturer, ADMA Biologics, believes that not needing refrigeration will lead to better distribution of the products particularly in areas that may not have adequate facilities to maintain uninterrupted cold storage. Limited amounts of time at room temperature have not resulted in any loss of effectiveness or impact on the safety of the drugs. Labeling for all IVIG products includes a boxed warning that using any of them may increase the risk of blood clots or kidney damage, which could cause kidney failure. Revised prescribing information for Asceniv is posted here; for Bivigam, here.

Recalls

On March 6, 2024, Thea Pharmaceuticals recalled one lot of Betimol^® (timolol ophthalmic solution) 0.5%, 15mL, due to a potential quality defect. This defect can compromise the container closure which may expose patients to bacterial contamination. Betimol is a non-selective beta-adrenergic antagonist used for the treatment of elevated intraocular pressure in patients who have ocular hypertension or open-angle glaucoma. For more information about the recall, see here.

On March 8, 2024, B. Braun Medical Inc. recalled two lots of potassium chloride (KCl) concentrate 2mEq/mL injection. The recall was initiated because there could be a potential leak on the bag which could result in microbial contamination and the potential for bloodstream infections. Potassium chloride is an electrolyte supplement used to treat or prevent low blood levels of potassium. For full details about the recall, see here.