On May 1, 2023 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to ERAS-801 for the treatment of adult patients with glioblastoma (GBM) with epidermal growth factor receptor (EGFR) gene alterations (Press release, Erasca, MAY 1, 2023, View Source [SID1234639356]). ERAS-801 is an orally bioavailable, small molecule EGFR inhibitor that exhibited substantial central nervous system (CNS) penetration in animal studies.
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FTD is designed to help drugs reach patients faster by facilitating the development and expediting the review of drugs with the potential to fill an unmet medical need by treating a serious or life-threatening condition. Programs that receive FTD benefit from early and frequent interactions with the FDA during the clinical development process and, if relevant criteria are met, the FDA may consider reviewing portions of a marketing application before the sponsor submits the complete application.
"Receiving FTD from the FDA underscores the serious unmet medical need in patients with GBM and reinforces the promise that ERAS-801 may offer as a differentiated treatment option," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "GBM is an aggressive malignancy with high rates of relapse and a five-year survival rate below 10%. While over half of GBM cases are driven by EGFR alterations and/or amplifications, there are no approved EGFR inhibitors for the treatment of GBM due to the lack of sufficient brain penetration to treat primary brain tumors as well as lack of activity against EGFR alterations observed in GBM, such as EGFRvIII. To help overcome these limitations, ERAS-801 was specifically designed to have high CNS penetration and broad activity against both oncogenic and wildtype EGFR. We look forward to working closely with the FDA to expedite clinical development of ERAS-801 for these patients and anticipate reporting initial monotherapy data from the Phase 1 THUNDERBBOLT-1 trial in recurrent GBM (rGBM) in the second half of 2023."
ERAS-801 was designed and developed by a renowned team of cancer researchers—Michael Jung, Ph.D., Timothy Cloughesy, M.D., and David Nathanson, Ph.D.
About ERAS-801
ERAS-801 is a highly potent, selective, reversible, and orally available small molecule EGFR inhibitor with significantly enhanced CNS penetration. In animal models, ERAS-801 had a brain-to-plasma partition coefficient, Kp, of 3.7 and a corresponding unbound partition coefficient, Kp,uu, of 1.2, which was up to four times higher than approved EGFR inhibitors, suggesting that approximately 100% of the free drug in plasma is able to cross the blood-brain barrier (BBB). At clinically relevant exposures across 30 patient-derived GBM models that are intended to represent the heterogeneity of GBM, ERAS-801 demonstrated a survival benefit in 13 out of 14 (93%) EGFR mutant and/or amplified models and had statistically significantly higher brain penetrance and prolonged survival compared to approved EGFR tyrosine kinase inhibitors, including osimertinib, lapatinib, and erlotinib. ERAS-801 is currently being evaluated as a monotherapy in THUNDERBBOLT-1, an ongoing Phase 1 trial in patients with rGBM.
About THUNDERBBOLT-1
THUNDERBBOLT-1 is evaluating the safety, tolerability, and preliminary efficacy of ERAS-801 as a monotherapy in patients with rGBM. The dose escalation portion will determine the recommended dose, which will then be used during the dose expansion portion to further evaluate the efficacy and safety of ERAS-801. Future sub-studies of THUNDERBBOLT-1 may potentially explore ERAS-801 in combination with other agents and in broader patient types. Initial Phase 1 data from THUNDERBBOLT-1 are anticipated in the second half of 2023.