FORE Biotherapeutics Receives Breakthrough Therapy Designation for Plixorafenib

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PHILADELPHIA–(BUSINESS WIRE) April 1, 2026 –FORE Biotherapeutics, a registration stage company dedicated to developing targeted therapies to treat patients with cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to plixorafenib for the treatment of adult patients with BRAF V600E-mutated high-grade glioma (HGG). Fore Bio believes this is the first BTD granted to a targeted therapy for HGG. Plixorafenib is a novel BRAF inhibitor that is a dimer breaker with high selectivity for BRAF alterations.

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  • Designation granted by FDA recognizes the potential of plixorafenib, a novel, investigational paradox breaker and BRAF inhibitor, to provide substantial improvement over available therapies
  • First Breakthrough Therapy Designation granted to a targeted therapy for High-Grade Glioma (HGG) is in addition to Fast Track Designation and Orphan Drug Designation plixorafenib already received encompassing CNS tumors
  • Topline results from Fore Bio’s FORTE Basket evaluating plixorafenib monotherapy for recurrent or progressive BRAF V600 primary CNS tumors by the end of 2026
  • Fore Bio believes the primary analysis from this CNS basket, if positive, would support the submission of a New Drug Application to the U.S. FDA under the Accelerated Approval pathway

    • The FDA granted this BTD based on data from approximately 25 patients treated in the completed Phase 1/2a clinical trial and ongoing Phase 2 FORTE basket evaluating plixorafenib in BRAF V600E-mutated central nervous system (CNS) tumors. The CNS tumors treated in FORTE include HGG, low-grade gliomas (LGG), and other primary brain and spinal cord tumors in adults and children. BTD is designed to speed the development and regulatory review of new medicines that are intended to treat a serious or life-threatening condition and that have shown encouraging early results, which demonstrate substantial improvement on one or more clinically significant endpoints (e.g., improved efficacy or improved safety with similar efficacy, etc.), over available therapies.

    “High-grade gliomas are aggressive primary brain tumors associated with poor outcomes despite multimodality treatment approaches,” said Macarena de la Fuente M.D., Chief, Neuro-Oncology Division, Department of Neurology, Sylvester Comprehensive Cancer Center, 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.”

    “The granting of Breakthrough Therapy Designation is a significant development milestone for plixorafenib and 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,” said Stacie Peacock Shepherd, M.D., Ph.D., Chief Medical Officer of Fore. “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 CNS tumors, including glioblastoma and other high-grade gliomas. The maturation of the data from FORTE may help validate these findings, with BTD status further accelerating the delivery of this promising therapy to patients. 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.”

    Data from the Phase 1/2a trial, which were previously presented at ASCO 2023 and SNO 2023, show that plixorafenib achieved a 67% overall response rate (ORR) in a pre-specified subgroup of patients with refractory MAPK inhibitor naive BRAF V600-mutated primary CNS tumors with robust anti-tumor activity further supported by duration of response (DOR), and clinical benefit rate (CBR) across BRAF-altered tumor types and CNS histologies. As of the last reporting, the BRAF V600E primary CNS basket of the FORTE study met the pre-specified interim analysis, with the Independent Data Monitoring Committee (IDMC) supporting that the study may continue as planned on the basis of responses assessed by blinded independent central review (BICR), in addition to the IDMC’s ongoing oversight for safety.

    BTD provides Fore with more frequent and intensive guidance from and dialogue with the FDA, including the involvement of senior reviewers, as well as eligibility for rolling and priority review of the marketing application. These benefits have the potential to accelerate the development and review of plixorafenib.

    Plixorafenib previously received Fast Track Designation for the treatment of patients with cancers harboring BRAF Class 1 (V600) and Class 2 (including fusions) alterations who have exhausted prior therapies and Orphan Drug Designation (ODD) for the treatment of primary brain and CNS malignancies. These, in addition to the BTD, continue to support the development of plixorafenib for the treatment of BRAF-altered primary CNS tumors in adults and children as the broader data set from FORTE continues to mature to provide a sufficient number of patients to support a robust benefit-risk profile across refractory high grade and low grade CNS biomarker-selected histologies.

    About the Global Phase 2 FORTE Basket StudyThe registration-intended FORTE Master Protocol is a global Phase 2 clinical trial which includes four sub-protocol baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are recurrent or progressive BRAF V600 primary CNS tumors, solid tumors with BRAF fusions and rare BRAF V600 mutated solid tumors. As part of the Bayesian adaptive design of the trial, interim efficacy analyses are conducted in each basket, for which the company reported a positive outcome from the BRAF V600 CNS basket in the third quarter of 2025.

    About BRAF Altered Recurrent Primary CNS TumorsBRAF altered recurrent primary CNS tumors represent a high unmet medical need and a large market opportunity for plixorafenib. In the advanced treatment setting, patients are offered currently approved therapies, but those therapies have significant limitations in efficacy, tolerability, and safety.

    About PlixorafenibPlixorafenib is a novel BRAF inhibitor, with a unique mechanism of action that functions both as a dimer and paradox breaker, and that has demonstrated a differentiated and compelling monotherapy profile in clinical studies. In a previously conducted Phase 1/2 study, in patients with MAPK inhibitor naïve BRAF V600 primary recurrent CNS tumors (n=9), plixorafenib monotherapy demonstrated an ORR of 67% and a clinical benefit rate of greater than 75%. In patients with V600 alterations who were MAPK inhibitor naïve, plixorafenib achieved a 42% response rate with prolonged duration of response (mDOR 17.8 months), with a clinical benefit rate of >70%. Plixorafenib also demonstrated a favorable safety and tolerability profile across tumor types, including relative to existing standard of care treatments for various BRAF altered tumors, with a discontinuation rate due to drug-related adverse events of less than 2%. Fore believes plixorafenib has the potential to overcome the limitations of currently available BRAF inhibitors through its unique mechanism of action targeting BRAF, while avoiding the limitations of the earlier generation BRAF inhibitors that led to rapid recurrence of disease and the need for combination with a MEK inhibitor.

    About FORE Biotherapeutics

    Fore is a registration stage targeted oncology company dedicated to developing innovative treatments that provide better outcomes for patients with the hardest-to-treat cancers. The Company’s lead asset plixorafenib (FORE8394; formerly PLX8394) is a V600 and non-V600 BRAF inhibitor rationally designed with a first-in-class mechanism to address treatment gaps from 1st and 2nd generation BRAF inhibitors. For more information, please visit www.fore.bio or follow us on X and LinkedIn.

    Source: FORE Biotherapeutics

    Source: HealthDay

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    Posted : 2026-04-03 08:59

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