FDA Approves First Therapy for Rare Type of Non-Cancerous Tumors

WASHINGTON — The Food and Drug Administration on Tuesday approved Ogsiveo tablets for adult patients with progressing desmoid tumors, a rare subtype of soft tissue sarcomas.

Desmoid tumors are non-cancerous but can be locally aggressive, invading surrounding structures and organs, causing pain and disability.

Although surgical removal has historically been the treatment of choice, there is a high risk that the tumor will return or that other health challenges will occur after removal; as a result, systemic therapies — cancer treatments targeting the entire body — are increasingly being evaluated in clinical trials. 

“Our team is honored to deliver the first FDA-approved therapy for patients with desmoid tumors,” said Saqib Islam, chief executive officer of SpringWorks Therapeutics Inc., the manufacturer of Ogsiveo, in a written statement.

“This community has been waiting for an effective treatment that not only shrinks their tumors but also significantly improves pain, which is the most debilitating symptom reported by people living with desmoid tumors,” Islam continued. 

“We are pleased with the broad label, which includes all progressing adult patients and specifically references improvement in pain, and believe Ogsiveo has the potential to become the new standard of care for people living with these devastating tumors,” he said. 

The effectiveness of Ogsiveo (nirogacestat) was evaluated in an international, multicenter, randomized, double-blind, placebo-controlled trial in 142 adult patients with progressing desmoid tumors not amenable to surgery. 

Patients were randomized to receive 150 milligrams of Ogsiveo or placebo orally, twice daily, until disease progression or unacceptable toxicity. 

The main efficacy outcome measure was progression-free survival, in other words, the length of time after the start of treatment for which a person is alive and their cancer does not grow or spread. 

Objective response rate — a measure of tumor shrinkage — was an additional efficacy outcome measure. 

The pivotal clinical trial demonstrated that Ogsiveo provided clinically meaningful and statistically significant improvement in progression-free survival compared to placebo. 

Additionally, the objective response rate was also statistically different between the two arms with a response rate of 41% in the Ogsiveo arm and 8% in the placebo arm. 

The progression-free survival results were also supported by an assessment of patient-reported pain favoring the Ogsiveo arm, the agency said. 

The most common side effects seen in at least 15% of the patients in the trial were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection and dyspnea. 

Ogsiveo was granted priority review under which the FDA’s goal is to take action on an application within six months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition compared to available therapies. 

Ogsiveo also received FDA fast track and breakthrough therapy designations for the indication noted above, as well as orphan-drug designation for treatment of desmoid tumors. 

Orphan-drug designation provides incentives to assist and encourage drug development for rare diseases.

“Desmoid tumors can have a significant impact on people’s lives and are difficult to manage due to their invasive nature and high rates of recurrence,” said Dr. Mrinal M. Gounder, sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center in New York City and an investigator in the phase 3 DeFi trial.  

“Ogsiveo is a highly innovative therapy with efficacy data demonstrating both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms,” Gounder continued. 

“As a treating physician, it was encouraging to see in the DeFi trial that Ogsiveo achieved statistically significant and clinically meaningful improvements across the primary and all key secondary endpoints, while also having a manageable safety profile. This approval represents an important therapeutic advance for patients,” Gounder concluded.

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