Desmoid tumors are rare growths that form in connective tissues, such as tendons and ligaments. Although they can affect anyone, they are more common in women. Desmoid tumors are not cancer, but they can keep growing and may cause pain, limit movement, or press on nearby tissues and organs.
Desmoid tumors that grow closer to the surface of the body are less likely to cause serious problems. In contrast, desmoid tumors that form deeper inside the body (such as in the abdomen, within the tissues around internal organs, or deep within muscles) are more likely to grow in ways that can affect nearby organs, blood vessels, and nerves. Because of their location, these deeper tumors may be harder to treat.
Ogsiveo (nirogacestat) is a prescription medicine for treating desmoid tumors in certain people. Ogsiveo is the first medicine specifically approved by the FDA for this condition.
This article explains how Ogsiveo works, how it was studied, how to take it, and what you can expect if your health care provider recommends this treatment.
Is Ogsiveo Right for My Desmoid Tumor?
Ogsiveo is FDA-approved for adults with desmoid tumors that are growing or getting worse (progressing) and need treatment that works throughout the body (systemic treatment).
Not everyone with a desmoid tumor needs systemic treatment right away. Some tumors can be removed by surgery, and some stay the same size for a long time. In these cases, your health care provider may suggest watching the tumor closely — or waiting to see if it comes back after surgical removal — before starting treatment.
To decide if Ogsiveo is right for you, your health care provider will see if your tumor is getting worse, causing symptoms or problems with nearby tissues or organs, or making daily activities harder.
Because desmoid tumors can act differently, treatment choices are often based on your individual needs. Your health care provider can help decide if Ogsiveo may be a good choice for you.
How Does Ogsiveo Work for Desmoid Tumors?
Gamma-secretase is an enzyme that helps activate certain proteins involved in cell communication. One of these proteins is called the Notch receptor. Normally, the Notch receptor helps cells send and receive signals that control important processes such as growth, development, and repair.
To do its job, the Notch receptor must be activated by the gamma-secretase enzyme. Once activated, the Notch receptor can send signals inside the cell that influence how the cell behaves.
Ogsiveo works by blocking the gamma-secretase enzyme. When gamma-secretase is blocked, the Notch receptor cannot be activated as easily, which reduces Notch signaling inside cells.
In some desmoid tumors, the Notch pathway may become dysregulated, meaning it is more active than it should be or does not work properly. When this happens, Notch signaling can turn on pathways that help tumor cells grow, survive, and continue multiplying. By blocking activation of the Notch receptor, Ogsiveo may help interrupt these growth signals. As a result, Ogsiveo may slow tumor growth and cause tumors to shrink.
How Was Ogsiveo Studied?
Ogsiveo was studied in a clinical trial called DeFi. The study included adults with desmoid tumors that were getting worse (progressing).
To join the study, adults had to have a desmoid tumor that showed signs of growing or worsening within the previous year. Participants either had not yet received treatment for a progressing desmoid tumor that could not be treated with surgery alone, or their tumor had returned or continued to grow despite previous treatment. People whose tumors posed an immediate serious health risk were not allowed to join the study.
The study included 142 adults from the U.S., Canada, and Europe. Here are some key characteristics of the group, as of the start of the study:
- The median (midpoint) participant age was 34 years, and ages ranged from 18 to 76 years.
- 65% were women, and 35% were men.
- Most participants (83%) were White, 6% were Black, 3% were Asian, and 8% were of other races or did not report their race; some were Hispanic/Latino (7%) or had unknown ethnicity, but most (86%) identified as non-Hispanic/Latino.
- Most participants (77%) had desmoid tumors located outside the abdomen (the area containing organs such as the stomach and intestines). The other 23% of participants had tumors located inside the abdomen or had tumors both inside and outside the abdomen.
- Most people were able to care for themselves and continue their usual daily activities, although some had symptoms that caused mild limitations.
- 41% of people had more than one desmoid tumor, while the remaining 59% had a single tumor.
- Most participants had previous treatments such as surgery, radiation therapy, chemotherapy, or certain medicines.
- Half of the participants reported a pain score of 2 or higher (on a scale of 0-10, with higher scores reflecting worse pain). About 41% of participants had uncontrolled pain at the start of the study, meaning they reported a pain score of 4 or higher despite their current treatment or management strategies.
Participants were randomly assigned to receive either Ogsiveo or a placebo (a pill containing no medicine). Neither the participants nor the researchers knew who was taking Ogsiveo during the study. Participants took Ogsiveo or placebo tablets twice daily.
People continued treatment until their disease worsened, they experienced unacceptable side effects, they chose to leave the study, or the study ended.
The main goal of the study was to see how long a person lived without their tumor getting worse.
After the main part of the study was over or if a patient’s disease progressed, some people were given the option to continue in an extended part of the study where everyone received Ogsiveo.
What Were the Main Benefits of Ogsiveo Seen in Studies?
The DeFi study found that Ogsiveo worked better than placebo for adults with progressing desmoid tumors.
The main outcome researchers measured was progression-free survival (PFS), which is the length of time a person lived without their tumor getting worse.
At the time of the analysis, participants had been followed for about 16 months. During that period, disease progression or death occurred in 37 people who received placebo and 12 people who received Ogsiveo.
Among the people who had disease progression:
- Most of these events happened because the tumor grew. Tumor growth seen on imaging scans occurred in 11 people taking Ogsiveo and 30 people taking placebo.
- Some people also experienced worsening symptoms that required additional treatment. This occurred in one person taking Ogsiveo and six people taking placebo.
One person in the placebo group died during the study, while no deaths occurred in the Ogsiveo group.
Overall, people who received Ogsiveo had a 71% lower risk of disease progression or death than those who received placebo.
After one year, an estimated:
- 85% of the Ogsiveo group had not experienced disease progression.
- 53% of the placebo group had not experienced disease progression.
After two years, an estimated:
- 76% of people on Ogsiveo remained free from disease progression.
- 44% of people on placebo remained free from disease progression.
The study found similar benefits across different types of participants, including men and women, people with tumors in different locations, those with one or multiple tumors, and those with or without previous treatment.
Your results may differ from what was seen in studies.
What Other Benefits of Ogsiveo Were Seen in Studies?
The DeFi study was mainly designed to measure PFS, as explained above, but the researchers also looked at other outcomes.
Response rate. The study looked at how many participants had a treatment response — in other words, how many people experienced tumor shrinkage.
- The results showed that 41% of people treated with Ogsiveo had tumor shrinkage, compared with 8% of those who received placebo.
- Some participants experienced a complete response, meaning no tumor could be seen on imaging scans. Complete responses occurred in 7% of people who received Ogsiveo, while no complete responses were reported in the placebo group.
Tumor size. The study also measured changes in tumor size over time. Overall, tumors became smaller in people taking Ogsiveo, while little change was seen in the placebo group.
Quality of life. In addition, the study looked at symptoms and quality of life. Compared with placebo, people taking Ogsiveo generally reported less pain and improved ability to carry out daily activities.
Keep in mind that real-life experience may be different from study results.
How Is Ogsiveo Taken, and What Can I Expect During Treatment?
The recommended dosage of Ogsiveo is 150 mg by mouth twice a day, taken with or without food.
Treatment usually continues until the tumor gets worse or side effects become too difficult to manage.
Various tests are required before and during Ogsiveo treatment to make sure it is safe for you to start or continue taking it. Monitoring may include:
- Pregnancy test before treatment
- Blood tests to check liver function
- Blood tests to check phosphate and potassium levels
- Skin exams to look for new skin cancers
- Tracking changes in menstrual cycles, fertility, or the signs of ovarian problems
Be sure to attend all scheduled appointments and lab visits while taking Ogsiveo. These visits can help your health care provider identify and manage the side effects.
Your health care provider may lower your dose, temporarily stop the treatment, or permanently stop Ogsiveo if you have certain side effects. Do not change your dose or stop taking Ogsiveo unless your health care provider tells you to do so.
Ogsiveo can cause side effects. The most common one is diarrhea. Your health care provider may recommend antidiarrheal medicines to manage it.
Contact your health care provider if you have severe diarrhea, persistent nausea or vomiting, signs of liver problems (such as yellowing of the skin or eyes), unusual skin changes, changes in your menstrual cycle, or any side effect that does not improve.
Your health care provider can help you understand the possible benefits and risks and decide whether Ogsiveo may be right for you.
Is There Any Cost Assistance Available for Ogsiveo?
A cost assistance program is available from SpringWorks Therapeutics, the drugmaker of Ogsiveo, which may reduce the amount you pay. Whether you qualify to enroll may depend on the type of insurance you have or if you are uninsured. For more information about Ogsiveo copay savings and patient support programs, visit www.ogsiveo.com/patient-support-program or call 844-227-3755.
