New Indication for Spravato as First Monotherapy for Treatment-Resistant Depression

On Jan. 21, 2025, the US Food and Drug Administration (FDA) approved Spravato^® (esketamine – Johnson & Johnson) for an additional indication, with or without an antidepressant taken by mouth, to treat adults with treatment-resistant depression (TRD). This marks the only monotherapy approved for this indication. Approved in 2019, this N-methyl-D-aspartate (NMDA) receptor antagonist was initially approved along with an oral antidepressant for adult patients who have major depression that has not been relieved by two or more appropriate length and dose rounds of treatment with other antidepressants and TRD. Over 21 million American adults have experienced at least one major depressive episode, and one-third of adults with major depressive disorder (MDD) will not respond to two oral antidepressants, classifying them as having TRD. About 86% of patients do not achieve remission from depression after trying their third oral antidepressant. The study supporting this approval demonstrated that 7.6% of participants taking a placebo and 22.5% of participants taking Spravato achieved remission. There was also a superior improvement in depressive symptoms when compared to placebo at 24 hours. No new safety concerns were identified. However, it does have a boxed warning, a risk evaluation and treatment strategy (REMS), and a patient Medication Guide detailing possible sedation, dissociation, suicidal thoughts, and misuse associated with using Spravato. Spravato is a CIII, single-use nasal spray device containing 28mg delivered in two sprays. Updated prescribing information will be available on the Drugs@FDA drug database at www.fda.gov.

Grafapex Approved for Stem Cell Transplant

The FDA approved Gradapex^™ (treosulfan – Medexus) on Jan. 22, 2025, with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients one year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). In AlloHSCT, stem cells are collected from a donor rather than the patient and requires conditioning therapy, typically with a busulfan-containing regimen. Gradapex is a first-in-class bifunctional alkylating agent that was compared to a busulfan-containing regimen, showing non-inferiority in two-year event free survival.  Musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting were the most commonly observed adverse events. The recommended treosulfan dose is 10g/m2 daily on days -4, -3, and -2 in combination with fludarabine 30mg/m2 on days -6, -5, -4, -3, and -2, and alloHSCT infusion on day 0. The launch is expected during the first half of 2025, but the cost is not known at this time. Complete prescribing information for Grafapex will be available on the Drugs@FDA drug database at www.fda.gov.

First Generic to Namzaric Launched

On Jan. 23, 2025, Amneal announced that the FDA approved memantine/donepezil 14-10mg and 29-10mg extended-release tables, the first AB-rated generic to reference to AbbVie’s Namzaric^®. Amneal’s generic was granted 180 days of exclusivity and is indicated for treating patients with moderate to severe dementia associated with Alzheimer’s disease. As of November 2024, annual sales for memantine/donepezil were approximately $88 million. Full prescribing information will be available on the Drugs@FDA drug database at www.fda.gov.

MedWatch Updates

Epinephrine Nasal Solutions Warning

On Jan. 16, 2025, the FDA warned healthcare professionals not to use unapproved epinephrine nasal solutions manufactured by BPI Labs LLC and Endo USA as they have been confused with FDA-approved injectable epinephrine products. The packaging is similar, and both the nasal solution and injectable products are manufactured by the same companies. There is potential for healthcare professionals to accidentally inject the nasal solution instead of the injection product. Nasal solutions are not required to be sterile, which can cause harm if injected.  Endo USA voluntarily recalled the solution on Dec. 20, 2024; however, BPI has not acted to remove its unapproved drug from the market.

New Boxed Warning for Glatiramer Acetate

On January 22, 2025, the FDA issued a drug safety communication warning about the rare risk of anaphylaxis associated with glatiramer acetate. This medication is used to treat relapsing forms of multiple sclerosis and was initially approved in 1996 under the brand name Copaxone^® (Teva). It is now available as a branded generic, Glatopa^® (Sandoz), along with several other generics. Glatiramer acetate is administered as a subcutaneous (SC) injection, either daily or three times a week. A boxed warning was added to both the prescribing information and the patient Medication Guide, indicating that this serious allergic reaction can occur at any time during treatment, even months or years after starting therapy. Symptoms of anaphylaxis most commonly appear within one hour of the injection. Updated prescribing information will be accessible on the Drugs@FDA drug database at www.fda.gov.

Updated DrugWatch Document Available

The Emerging Therapeutics department has updated DrugWatch, a document that highlights near-term pipeline drugs as well as potential new generic opportunities. The DrugWatch document is attached.