The First Drug to Treat Desmoid Tumors Is Here

Fact checked by Nick Blackmer

Key Takeaways

• The FDA approved Ogsiveo by drugmaker SpringWorks Therapeutics to manage desmoid tumors in adults—the first drug of its kind.

• The drug helps reduce the size of the non-cancerous tumors and alleviate symptoms associated with the condition, including pain.
  

In November, the FDA approved the drug Ogsiveo (nirogacestat) by pharmaceutical company SpringWorks Therapeutics for the treatment of desmoid tumors.

Desmoid tumors are a rare type of connective-tissue tumor. Also known as aggressive fibromatosis or desmoid-type fibromatosis, these non-cancerous tumors typically affect people between 15 and 60 years old. The tumors are most often found in the abdomen, shoulders, upper arms, and thighs and can cause symptoms including pain, tingling, swelling, and decreased mobility, which can all affect daily functioning.

Ogsiveo is a prescription medication taken twice daily as a tablet. The ideal candidate for Ogsiveo is an adult with a progressing desmoid tumor requiring systemic treatment, including where surgery is not possible or advisable.

“The FDA continues to address unmet medical [needs] and advance the development of safe and effective therapies for the millions of Americans whose lives are affected by rare tumors,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research said in a press release.

“Desmoid tumors are rare tumors that can lead to severe pain and disability,” he said. “Today’s approval will offer the first approved treatment option for patients beyond surgery and radiation.”

Second Life for a Failed Alzheimer’s Drug

Ogsiveo was originally developed for the treatment of Alzheimer’s disease, but it was never approved for the condition, Chandrajit Premanand Raut, MD, chief of surgical oncology at Brigham and Women’s Hospital in Boston and professor of surgery at Harvard Medical School, told Verywell. In clinical trials, it showed promise for treating desmoid tumors, leading to further research.

From May 2019 to August 2020, 142 adult participants with a history of progressing desmoid tumors took part in a phase 3, international, double-blind, randomized, placebo-controlled trial. Seventy patients received a 150 milligram dose of Ogsiveo twice daily and 72 were given a placebo pill twice daily.

The findings from the trial, published in The New England Journal of Medicine, found that 41% of patients’ tumors were significantly reduced after they took Ogsiveo. After two years on the drug, the likelihood of being tumor-free was 76% with Ogsiveo compared to 44% with placebo.

“Most patients had shrinkage of their desmoid tumors on Ogsiveo and five had complete responses—as in the tumors completely disappeared,” Noah Federman, MD, a professor of pediatrics and orthopedics and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Pediatric Bone and Soft Tissue Sarcoma Program, told Verywell.

Importantly, on top of shrinking or eliminating the tumors, Ogsiveo showed a reduction in pain and symptom burden and an improvement of physical functioning.

“This is really a critical point that I cannot emphasize more,” Federman, who was an investigator on the Ogsiveo clinical trial, said. “Severe and often chronic pain coupled with impaired physical functioning and mobility are frequent complaints from our desmoid tumor patients. Improving or resolving these symptoms contributes to a major improvement in quality of life.”

Raut echoes this sentiment, adding that even though desmoid tumors are not cancerous or metastatic, the symptoms can be debilitating. In more serious cases, they can cause bowel perforation and significant pain that can lead to opioid dependence.

“Sometimes just even a small amount of shrinkage of the tumor without significant change in size can lead to improvement in symptoms,” Raut said.

Related: How a Desmoid Tumor Is Diagnosed

Why an Approved Medication Is a Game-changer

One of the reasons why people in the desmoid community are excited about this drug is because there hasn’t been an approved medication for the condition previously.

“Up until now, the treatment of desmoid tumors has been all over the place,” Federman said.

Ogsiveo is the first therapy specifically designed to treat the highly recurrent soft-tissue tumor.

“Soft-tissue tumors are a rare subset of all cancers in the U.S., and desmoid tumors represent a rare subset of these cancers. Overall, there are about 900 to 1,500 patients diagnosed with desmoid tumors in the U.S. each year,” Salman Punekar, MD, a medical oncologist at NYU Langone’s Perlmutter Cancer Center and an assistant professor of medicine at NYU Grossman School of Medicine, told Verywell.

Treatment for people with desmoid tumors depends on the size and location of the tumor, as well as the disease progression. Treatment can include monitoring the tumor (surveillance) or interventions such as surgery, chemotherapy, radiation, or medications such as tyrosine kinase inhibitors.

Related: Desmoid Tumor Treatment

Surgery, which was once a primary treatment, has become less common due to high morbidity and postsurgical recurrence rates.

“No one option has been largely effective, and all come with potential major morbidity and side effects,” Federman said. “Furthermore, none of the medical options were FDA approved, so that was a whole other can of worms, sometimes [resulting in] fighting with insurers over medication coverage. Can you imagine telling a patient day in and day out that we have no medication approved for this disease, so we are going to try things off-label with no great idea how they might work in desmoid tumors? That has been where we have been for the past 50-plus years.”

Ogsiveo works by shrinking the desmoid tumor.

“Ogsiveo is a new type of medication called a γ-secretase inhibitor (gamma-secretase) which blocks the Notch signaling pathway, an important pathway that desmoid tumors use to grow,” Punekar said.

How to Take the Pill

Ogsiveo requires a prescription. The optimal duration of taking Ogsiveo is still unknown, Federman said, though most patients in clinical trials remained on the drug anywhere from six months to several years.

Experts are also unsure whether patients need to be on the treatment indefinitely or if they can take a break from it once their tumor responds to the medication.

Furthermore, Ogsiveo might cause harm to a fetus, so patients expecting or wanting to get pregnant should speak to their healthcare provider to understand the risk. There are also risks of new non-melanoma skin cancers, ovarian toxicity, and liver toxicity.

How Does Ogsiveo Work?

Nirogacestat is a gamma-secretase inhibitor that blocks the receptor for the Notch protein—a critical pathway in the growth of a desmoid tumor.

What Are the Side Effects?

In clinical trials, side effects of Ogsiveo were mostly mild and included diarrhea, nausea, fatigue, hypophosphatemia (phosphate deficiency), skin rash, stomatitis (inflammation of the mouth), headache, dermatitis acneiform (a skin reaction resembling acne), and vomiting.

“Ovarian dysfunction—now called ovarian toxicity—was also seen in women of child-bearing age in the [clinical trial],” Federman said. “This manifested as symptoms of menopause: hot flashes, not having menses (amenorrhea), and other symptoms.”

However, the trial reported that the side effect of ovarian dysfunction resolved in 74% of those affected, and stopped entirely once the patient went off the medication.

“No meaningful changes in male hormonal levels or adverse events pertaining to male reproductive potential were observed,” the researchers wrote.

How to Get Ogsiveo

Because Ogsiveo is FDA-approved for the treatment of desmoid tumors, if a patient has a prescription, it should be covered by their health insurance plan, depending on their coverage.

Federman said a specialty pharmacy will likely dispense the medication and that the drug should be widely available in the coming weeks. It’s important that patients speak to their healthcare provider to see if this medication might be suitable for them.

For eligible candidates, Federman believes it will make an impact.

Clinical trial participants have told Federman that the medication has allowed them to participate in the things many of us often take for granted, like going to school, going to work, lifting their children, walking short and long distances, exercising, and participating in social engagements.

“I am looking forward to writing my first prescription for nirogacestat in the coming weeks for a patient with progressive desmoid tumor,” he said.

Read the original article on Verywell Health.