In November 2023, the U.S. Food and Drug Administration (FDA) approved the first medication for desmoid tumors — nirogacestat (Ogsiveo). This article will cover what researchers and doctors know about nirogacestat to help you understand this desmoid tumor treatment.

What Is Nirogacestat?

Nirogacestat is a type of targeted therapy. That means it works by blocking the action of a certain molecular pathway. A molecular pathway is a series of actions, often involving proteins, that lead to cell changes. Desmoid tumors are linked with many molecular pathways. One in particular, called the Notch signaling pathway, is thought to play an important role in tumor growth. In people with desmoid tumors, the Notch protein can become overactive when it’s cut by an enzyme called gamma secretase.

Gamma secretase helps cut a bigger protein into a smaller one. The smaller protein can then enter a tumor cell’s nucleus (its center) and provide a growth signal. Nirogacestat is a gamma secretase inhibitor — it stops the enzyme from cutting the protein and prevents a growth signal from occurring.

Nirogacestat targets the Notch pathway, so researchers thought it might work for shrinking desmoid tumors. By slowing down the overactive Notch pathway, nirogacestat specifically targets desmoid tumors.

How Does Nirogacestat Differ From Other Targeted Therapy?

In cancer treatment, “targeted therapy” refers to medicine that stops the molecular pathways that make cancer grow. Desmoid tumors are considered benign (not cancerous), but treatment for desmoid tumors may involve medications that are also used to treat cancer. Until nirogacestat, no targeted therapies were specifically approved for use in desmoid tumors.

Targeted therapies approved for other conditions are sometimes used to treat desmoid tumors off-label. The National Cancer Institute defines this as “the practice of prescribing a drug for a different purpose than what the FDA approved.”

Who Might Benefit From Using Nirogacestat?

Nirogacestat is approved for adults who need systemic (whole-body) therapy because their desmoid tumors are progressing — they’re growing or causing other problems, such as bothersome symptoms. Systemic treatment usually refers to chemotherapy, immunotherapy, or targeted therapy.

What Do Clinical Trials Show?

A clinical trial performed by researchers from around the world showed that nirogacestat slows desmoid tumor growth. Clinical trials are research studies done in people to see if a treatment is safe and effective. The results of this clinical trial, known as the Desmoid Fibromatosis (DeFi) Trial, were published in The New England Journal of Medicine in 2023.

The DeFi trial involved 142 people with desmoid tumors. Half the participants received nirogacestat, and the other half got a placebo (nondrug pill), twice a day until their disease progressed or they dropped out because of drug side effects. The researchers found that nirogacestat led to less progression and more improvement in people with desmoid tumors.

Fewer People Taking Nirogacestat Progressed Over 2 Years

The researchers looked at tumor progression in both groups of participants. After two years, people who took nirogacestat had a 71 percent lower risk of their tumor progressing or of dying than those in the placebo group. This means nirogacestat prevented the desmoid tumor from getting worse compared with the placebo.

People Taking Nirogacestat Had Tumor Improvements

Objective response rate is a way to measure how well a treatment is shrinking a tumor. A higher objective response rate means that more people had tumor shrinkage. In the DeFi trial, people taking nirogacestat had a 41 percent objective response rate, whereas the placebo group had just an 8 percent rate. This means that, on average, more people had tumor shrinkage while taking nirogacestat than those taking the placebo.

People Felt Better Taking Nirogacestat

Participants took surveys on how they felt before, during, and after treatment. People who took nirogacestat consistently reported feeling better compared with people who got the placebo. Specifically, people taking nirogacestat reported:

• Experiencing less tumor pain
• Feeling more physically able
• Having a better quality of life

What Are Nirogacestat’s Side Effects?

Like other drugs, nirogacestat can lead to side effects. According to prescribing information for nirogacestat, side effects that occurred in more than 15 percent of people included:

• Headache
• Hair loss
• Tiredness
• Nausea
• Cough
• Stomach pain
• Rash
• Mouth inflammation
• Shortness of breath
• Infection in the throat or upper airway
• Problems with ovary function

In the DeFi trial, the most common side effects were:

• Diarrhea
• Tiredness
• Nausea
• Low blood levels of phosphate
• Bumpy rash

Most (95 percent) of the reported side effects weren’t considered severe.

Who Shouldn’t Take Nirogacestat?

Nirogacestat may not be an option for everyone. If you’re pregnant or breastfeeding, you shouldn’t take nirogacestat. Also, it’s important to talk with your doctor to find out if any of your other medications could interact with nirogacestat and cause harm. If you take antacids, do so at a different time from nirogacestat. Medications that involve certain enzymes can also be harmful for people who are using nirogacestat.

If you’re considering trying nirogacestat for your desmoid tumor, talk to your doctor. They’ll help you understand if you’re a good candidate.

Talk With Others Who Understand

On MyDesmoidTumorTeam, people share their experiences with desmoid tumors, get advice, and find support from others who understand.

Have you taken nirogacestat or discussed this new treatment option with your doctor? Let others know in the comments below.