New Immunoglobulin, Alyglo, Approved

GC Biopharma was granted approval from the U.S. Food and Drug Administration (FDA) on Dec. 15, 2023, for Alyglo™(immune globulin intravenous [IV], human-stwk) 10% liquid. It is indicated to treat primary immunodeficiencies (PI) for patients who are at least 17 years old. As estimated by the Jeffrey Modell Foundation, a not-for-profit organization that advocates for PI research and treatment, about 80,000 patients in the United States have been diagnosed with PI. Including a large group of inherited conditions, PI symptoms range from mild to life-threatening. As a result of inadequate immune function, patients who have a PI typically experience frequent, prolonged, and possibly severe infections. Many patients also have concomitant autoimmune diseases. Standard therapy for many PIs is to replace the missing natural immunoglobulin (IG), usually through IV infusions of immunoglobulin products (IVIG) derived from donated human blood plasma. Doses of Alyglo depend on the patient’s weight with a recommended range of 300mg/kg to 800mg/kg once every 21 days or 28 days. Although several other IVIG products are FDA-approved to treat PI, Alyglo is processed to minimize its content of coagulation factor XIa, reducing the possibility that it may cause blood clots. Its labeling still has to display the same boxed warning required for all IVIGs, however — that they may be associated with blood clots and kidney damage that could result in acute kidney failure.

New Dosage Form and Indication for Zoryve

A new dosage form of roflumilast, Zoryve^® (Arcutis Biotherapeutics) Topical Foam, 0.3%, was FDA approved on Dec. 15, 2023. It is indicated to treat seborrheic dermatitis in individuals who are at least nine years old. Applied once every day, it is a topical phosphodiesterase-4 (PDE4) inhibitor with no limitations on how long it can be used. Its foam formulation makes it gentler on the skin and easier to use on hairy areas than creams or ointments. Arcutis estimates that approximately 10 million Americans have some degree of seborrheic dermatitis, which produces itchy flaky scales in oily areas of skin, primarily the face and scalp. Although it is not contagious and no reason for flare-ups may be apparent, seborrheic dermatitis may be caused by a reaction to a normal body yeast (malassezia), an immune malfunction, or excessive oil. Symptoms may be worsened by fatigue, stress, very hot or cold weather, and other medical conditions, including acne, HIV/AIDS, obesity, and Parkinson’s disease. Presently, topical treatment for seborrheic dermatitis depends mainly on corticosteroid products and antifungal agents, such as ketoconazole. Typically, corticosteroids are not used continuously due to their possibility of serious side effects, including osteoporosis. Other topical treatments may include coal tar, salicylic acid, and selenium sulfide.Eucrisa® (crisaborole) ointment, 2%, another topical PDE-4 inhibitor, currently is approved in the U.S. only to treat mild-to-moderate atopic dermatitis. In a clinical study of Zoryve Foam, about one-half of the patients treated with it had complete clearance after eight weeks. The launch is planned for the end of January 2024. It will be available in 60gm cans that have a wholesale acquisition cost (WAC) of $858/can – the same cost as one 60gm tube of Zoryve Cream, 0.03%. The cream formulation was FDA-approved in July 2022 to treat plaque psoriasis for patients who are at least six years old. Oral roflumilast is indicated for the treatment of chronic obstructive pulmonary disease (COPD). Look here for Its prescribing information.

Keytruda and Padcev Receive Full FDA Approval for Urothelial Carcinoma

The FDA awarded an Accelerated Approval in April 2023, for the combination use of Keytruda^® (pembrolizumab) injection, and Padcev^® (enfortumab vedotin-ejfv) injection, for treating urothelial (bladder) cancer that has spread locally or distantly in adults. Based on positive results from the continuing clinical study, the indication for Merck’s programmed death receptor-1 (PD-1) inhibitor and Astellas/Pfizer’santibody/drug conjugate was fully approved on Dec. 15, 2023. According to the American Cancer Society (ACS), about 82,000 patients are diagnosed with bladder cancer each year – three times as many men as women. The majority of patients are over 55 years old. Approximately 90% of cases begin in the urothelial cells that line the inside of the bladder and adjacent areas. In the EV-302 clinical study, the risk of death was reduced by more than one-half and both progression-free survival (PFS) and overall survival (OS) times approximately doubled for patients using the Keytruda/Padcev regimen as compared with participants who used platinum-based chemo. In tandem with Padcev to treat advanced urothelial cancer, the recommended dose of Keytruda is 200mg administered through a 30-minute IV infusion about 30 minutes following a dose of Padcev on day one of each 21-day treatment cycle. Padcev is infused at 1.25mg/kg (up to 125mg) over 30 minutes on the first and eighth days of 21-day cycles. Keytruda has numerous other FDA approvals with and without other cancer drugs for treating various types of non-small cell lung cancer (NSCLC), some kidney cancers; some esophageal, stomach and head and neck cancers; as well as Merkel cell carcinoma, multiple myeloma and non-Hodgkin lymphoma. It also has indications for pediatric and adult patients whose cancers have specific genetic characteristics (biomarkers), rather than developing from a particular body tissue. Padcev also is FDA-approved as monotherapy for treating urothelial cancer that has progressed despite treatment with chemo that contains platinum, a PD-1 inhibitor, or a programmed death ligand-1 (PD-L1) inhibitor, such as Bavencio^® (avelumab). Because it may trigger severe, even fatal, skin reactions, Padcev has a boxed warning. Revised prescribing information is here for Keytruda and here for Padcev.

Full Approval for Tarpeyo

After data from a required clinical study confirmed effectiveness and impact on kidney function, the FDA converted its Accelerated Approval for Tarpeyo^® (budesonide – Calliditas Therapeutics) delayed-release capsules to full approval on Dec. 19, 2023. A new formulation of a corticosteroid that is used widely in multiple other dose forms for several allergic and inflammatory conditions, it was the first drug to be FDA-approved for lowering the decline of kidney function for adult patients who have primary Immunoglobulin A nephropathy (IgAN). Originally, its use was limited to patients whose condition is likely to deteriorate quickly, but the qualification for a rapid decline was changed to a risk of disease progression by the FDA, allowing the use of Tarpeyo for more patients who have IgAN. Many who have the condition eventually develop end-stage kidney disease, which often needs dialysis and/or a kidney transplant. Tarpeyo decreases the amounts of protein lost in urine by regulating antibodies that cause IgAN. Treatment with it is recommended to start at a urine protein-to-creatinine ratio of 1.5gm/gm or higher. Patients take four whole capsules (16mg) one hour or more before any food once every morning for eight and one-half months. For the next two weeks, doses are reduced to two capsules (8mg) per day and then treatment is ended. Following the end of treatment in the study, improved kidney function persisted for at least 15 months for study participants. The most common effects included peripheral edema, hypertension, muscle spasms, acne, and headache. Tarpeyo is available only through one specialty pharmacy. Prescribers must use specialized documents to order it and patients must be enrolled in a treatment plan for it to be dispensed. Complete prescribing information is here.

MedWatch Update

Ozempic

In a Safety Communication that was issued on Dec. 21, 2023, the FDA warned that some pen devices marketed in the U.S. as containing the prescription-only drug Ozempic^® (semaglutide) are fake. Although the FDA and the manufacturer of Ozempic have removed large numbers of the devices from the market, some may still be in distribution. Both the composition of the pen contents and the sterility of the needles used for injection are in question. Ozempic is injected once a week to treat diabetes and to lower the risk of heart attacks and strokes for patients who have diabetes and cardiovascular (CV) diseases. Because it contains the same drug as Wegovy^®, which is used for weight loss, some people may use it off-label to manage weight. People using the fake product may not have the expected health results, they may have serious side effects and they may be more likely to acquire infections from unsterile components of the devices. All of the counterfeit devices have the lot number NAR0074 and the serial number 430834149057. Individuals are warned not to purchase Ozempic from sources other than licensed pharmacies and to inspect each device and its packaging for false numbers. More information is in the FDA’s notice.