On June 22, 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 Orphan Drug Designation (ODD) to ERAS-801 for the treatment of malignant glioma, which includes glioblastoma (GBM) (Press release, Erasca, JUN 22, 2023, View Source [SID1234639353]). ERAS-801 is an orally bioavailable, small molecule EGFR inhibitor that exhibited substantial central nervous system (CNS) penetration in preclinical animal studies.

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Per FDA regulations, ODD is granted by the FDA to investigational therapies addressing rare medical diseases or conditions affecting less than 200,000 people in the United States. Orphan drug status provides benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees, and the potential for seven years of post-approval marketing exclusivity.

"GBM is an aggressive malignancy afflicting approximately 37,000 patients annually in the United States and Europe. Currently approved EGFR inhibitors are limited by insufficient CNS penetration to treat GBM and minimal activity against GBM-specific EGFR amplifications, mutations, and other molecular alterations, which contribute to high rates of relapse and a five-year survival rate below 10%," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "Receiving ODD recognizes both the importance of innovation for patients with GBM and the therapeutic potential of ERAS-801 to provide a targeted treatment option for these patients, who have a poor prognosis. This ODD follows the earlier Fast Track Designation granted to ERAS-801 by the FDA and underscores the urgency of finding new treatments for this patient population. The broad activity against both oncogenic and wildtype EGFR, high CNS penetration, and demonstrated ability to improve outcomes in over 90% of diverse EGFR-driven patient-derived glioma models support the potential for ERAS-801 to overcome current challenges with existing therapies. We anticipate reporting initial monotherapy data for ERAS-801 from the Phase 1 THUNDERBBOLT-1 trial in patients with recurrent GBM 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 bioavailable 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 were 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 recurrent GBM (rGBM). In April 2023, the FDA granted Fast Track Designation (FTD) to ERAS-801 for the treatment of adult patients with GBM with EGFR gene alterations. In June 2023, the FDA granted ODD to ERAS-801 for the treatment of malignant glioma, which includes glioblastoma.

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.