Plixorafenib given FDA breakthrough status for high-grade gliomas
Designation based on early data in BRAF V600E-mutated tumors
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The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to plixorafenib as a potential treatment for adults with high-grade gliomas carrying a mutation known as BRAF V600E.
The FDA gives this designation to therapies for serious conditions that have shown promising early results. It provides plixorafenib’s developer, Fore Biotherapeutics, with benefits such as more intensive guidance from the agency during development, with the goal of speeding the process.
“The granting of Breakthrough Therapy Designation is a significant development milestone for plixorafenib and reinforces our conviction in its unique mechanism of action which … underscores the potential of plixorafenib as a treatment option for patients living with difficult to treat cancers,” Stacie Peacock Shepherd, MD, PhD, Fore’s chief medical officer, said in a company press release.
High-grade gliomas are aggressive brain tumors
Gliomas are brain cancers that arise from the uncontrolled growth of glia, a diverse class of cells that support and protect nerve cells in the brain.
“High-grade gliomas are aggressive primary brain tumors associated with poor outcomes despite multimodality treatment approaches,” said Macarena de la Fuente, MD, of the University of Miami Miller School of Medicine. “In addition to their limited prognosis, patients experience substantial morbidity related to both the disease itself and the toxicities of current therapies. Therefore, there remains a critical need for novel treatments that are not only effective but also better tolerated.”
BRAF is a protein that helps control when cells divide. In many cancers, mutations in this protein drive uncontrolled growth of cancer cells. V600E is the most common cancer-driving BRAF mutation. Plixorafenib is an investigational oral therapy designed to block BRAF and stop the abnormal growth of cancer cells.
“BRAF alterations are an important actionable driver in the molecularly integrated clinical decision paradigm for the treatment of high-grade gliomas, and plixorafenib has demonstrated a differentiated profile in patients with primary [brain] tumors, including glioblastoma and other high-grade gliomas,” Shepherd said.
Early clinical data supported FDA breakthrough designation
The FDA’s decision to grant breakthrough designation was based on data from a completed Phase 1/2a trial and an ongoing Phase 2 study called FORTE (NCT05503797), which is testing plixorafenib in people with BRAF V600-mutated primary brain and central nervous system tumors, including high-grade gliomas.
According to Fore, which is sponsoring the trial, interim data from earlier studies showed that about two-thirds of patients (67%) in a specific subgroup of hard-to-treat brain tumors responded to the therapy, meaning their tumors shrank. The FORTE trial is recruiting participants at multiple sites worldwide, with topline results expected by the end of this year.
If data are positive, the company believes it would support the submission of a New Drug Application to the FDA under its Accelerated Approval pathway.
“We look forward to continued collaboration with the FDA to further advance plixorafenib and to advancing our FORTE basket trial in several types of BRAF altered malignancies,” Shepherd said, adding that the new FDA designation “reinforces our conviction in its unique mechanism of action which, further supported by the tolerability and efficacy profile seen in BRAF-altered tumors, underscores the potential of plixorafenib as a treatment option for patients living with difficult to treat cancers.”
