Understanding the FDA Approval of Veppanu: Your Questions Answered

On May 1, the breast cancer community reached a new milestone with the Food and Drug Administration (FDA) approval of Veppanu (vepdegestrant). This first-in-class therapy introduces a novel way to fight advanced disease, specifically for patients who have developed resistance to traditional treatments.

To help patients and caregivers navigate this news, CURE spoke with Dr. Komal Jhaveri, an oncologist at Memorial Sloan Kettering Cancer Center and a lead investigator in the clinical trials that led to this approval. Below, we answer the most pressing questions regarding this new treatment option, including some submitted by readers in the comments section of our social media pages.

Who is eligible for Veppanu?

The FDA has approved Veppanu for adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer. To qualify, a patient’s cancer must have progressed after at least one line of endocrine therapy.

How do I know if I have the ESR1 mutation?

The ESR1 mutation is a common way breast cancer cells learn to resist standard hormone therapies. To identify patients who will benefit from Veppanu, the FDA also approved the Guardant360 CDx as a companion diagnostic. This test uses a blood sample (liquid biopsy) to look for circulating tumor DNA to confirm the presence of the mutation.

What makes a PROTAC different from other treatments?

Veppanu is the first-ever proteolysis-targeting chimera (PROTAC) to receive FDA approval. While older drugs like tamoxifen or aromatase inhibitors work by blocking the estrogen receptor, a PROTAC takes a more aggressive approach.

“What is unique about the mechanism of action of this newer novel endocrine drug is that not only are we binding and targeting the estrogen receptor, but we're also trying to bind with the U3 ligase,” Jhaveri explained. This combined binding causes “proteasomal degradation” of the receptor. Essentially, the drug marks the cancer’s receptors for destruction, removing them from the cell entirely rather than just trying to sit on top of them.

How effective was the drug in clinical trials?

Approval was based on the VERITAC-2 trial, which compared Veppanu to the standard-of-care injectable therapy, Faslodex (fulvestrant). For the 270 patients in the trial with ESR1 mutations, the results were significant: the median progression-free survival, or the time patients lived without their disease spreading or worsening, was five months with Veppanu, compared to 2.1 months for those on Faslodex.

What are the side effects, and can I manage them at home?

According to Jhaveri, the safety profile is one of the most encouraging aspects of the data. Common side effects include fatigue, musculoskeletal pain and nausea.

“The most reassuring thing I can say is that yes, we can think about some fatigue and some nausea but it was predominantly low grade,” Jhaveri said. She noted that the trial saw very few high-grade toxicities and that “very few patients had to discontinue therapy due to toxicity,” which suggests these symptoms are well-managed without needing to stop treatment. Patients should be aware of a warning for QTc interval prolongation (a heart rhythm change), though Jhaveri noted that sub-studies showed no clinically worrisome increases in most patients.

How is Veppanu taken?

Veppanu is a convenient daily oral medication. The recommended dose is 200 mg, which should be taken with food.

When will the drug be available in pharmacies?

Although the FDA approved the drug early, there is usually a lag time before it is stocked in specialty pharmacies. Jhaveri estimates it will take “a minimum a few weeks to a couple of months” before patients can successfully fill their first prescriptions.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.