Stemline Therapeutics was granted approval from the U.S. Food and Drug Administration (FDA) for Orserdu^™ (elacestrant) tablets on Jan. 27, 2023. It is an oral selective estrogen degrader (SERD) indicated as second-line or later therapy to treat advanced breast cancer that is positive for estrogen receptors (ER+), negative for human epidermal growth factor receptors 2 (HER2-), and proven positive by diagnostic testing for estrogen receptor 1 (ESR1) gene mutations. It is used after previous treatment with an endocrine drug has failed. Orserdu can be prescribed for men as well as for postmenopausal women. Taken with food to decrease the likelihood of nausea and vomiting, the recommended daily dose is 345mg. The launch is expected soon through a limited small network of specialty pharmacies that will not include Accredo. A cost estimate is not yet available. Here is prescribing information.

At a Glance

• Brand (Generic) Name: Orserdu (elacestrant) 
• Manufacturer: Stemline Therapeutics, a Menarini Group Company
• Date Approved: Jan. 27, 2023
• Indication: to treat postmenopausal women and adult men, who have ER+/HER2-/ESR1-mutated advanced or metastatic breast cancer that has progressed despite one or more  endocrine therapies
• Dosage Forms Available: 86mg and 345mg tablets
• Launch Date: “soon”
• Estimated Annual Cost: Not yet available
• The most common cancer among women, breast cancer strikes about 300,000 new patients, including around 3,000 men, in the U.S. each year, according to the American Cancer Society (ACS).
• The large majority of newly diagnosed breast cancer cases are ER+/HER2-, and as many as 40% of metastatic breast cancers have ESR1 mutations, which generally are not susceptible to treatment with aromatase inhibitors — anastrozole, exemestane, and letrozole.
• Orserdu is the first FDA-approved drug to interfere with ESR1, a genetic mutation that promotes resistance to aromatase inhibition.
• In the Phase III clinical trial, the chances of death or cancer worsening were 45% less for patients taking Orserdu than for patients using current treatments of choice, either fulvestrant (an injectable SERD) or an aromatase inhibitor. The median progression-free survival (PFS) time was doubled for patients taking Orserdu (3.8 months vs 1.9 months).
• In studies, the most common side effects included diarrhea, fatigue, headache, nausea, and muscle/bone pain. Blood lipids should be watched because taking Orserdu may increase blood levels of cholesterol and triglycerides. Liver enzymes also may be elevated.
• Commonly, fulvestrant, tamoxifen (a non-steroidal anti-estrogen), or an aromatase inhibitor is used for the initial treatment of early breast cancer after tumors have been removed surgically. They can be used for metastatic cases, as well, but resistance to them develops somewhat rapidly.
• Chemotherapy (chemo) with one of the multiple approved regimens may be used for metastatic breast cancer that does not respond to endocrine therapy.
• Usually in combination with an aromatase inhibitor, drugs that inhibit cyclin-dependent kinases 4 and 6 (CDK4/6) also can be used to treat ER+/HER2- breast cancer. The ones approved in the U.S are Ibrance^® (palbociclib) plus letrozole, Kisqali^® (ribociclib) plus an aromatase inhibitor and Verzenio^™ (abemaciclib) plus fulvestrant.
• Some targeted therapies and immunotherapies also are indicated for HR+/HER2- metastatic breast cancers that have specific genetic mutations.
• The FDA awarded approval for Orserdu under its Fast-Track and Priority Review programs.