– OS and PFS Study endpoints met in large subgroup of patients with recurrent astrocytoma, IDH mutant grade 3 as defined by the 2021 WHO CNS Tumor Classification in Orbus Therapeutics’ Phase 3 STELLAR study –

– Eflornithine was previously granted Orphan Designation and Breakthrough Therapy Designation by U.S. Food and Drug Administration (FDA) –

PALO ALTO, Calif., Nov. 22, 2024 – Orbus Therapeutics, Inc., a private pharmaceutical company, today announced that the combination of eflornithine and lomustine achieved a clinically meaningful improvement in overall survival (OS) and progression free survival (PFS) compared to lomustine as a single agent for those patients with grade 3 IDH mutant astrocytoma who have progressed after irradiation and adjuvant temozolomide treatment.  This patient subpopulation represented the majority of patients enrolled in the Phase 3 STELLAR clinical trial.  The results were presented at the Society for Neuro-Oncology Annual Meeting held in Houston, Texas.

“For patients with recurrent grade 3 astrocytoma, a rare and fatal disease, there are very few available treatment options.  The last FDA approval of a chemotherapeutic agent for these patients was 25 years ago,” said Bob Myers, Chief Executive Officer, Orbus.  “We are impressed by these results, which would not have been attainable without the dedication and participation of patients, investigators, and study staff who made major contributions to the conduct of this study.”

The STELLAR study (NCT02796261) was designed to evaluate the efficacy and safety of eflornithine in combination with lomustine compared to lomustine alone in patients with anaplastic astrocytoma that recurs after surgery, irradiation and adjuvant temozolomide chemotherapy. The study enrolled a total of 343 patients and, importantly, it included a large subset (n=194) of grade 3 IDH mutant astrocytoma patients, as defined by World Health Organization (WHO) specified molecular markers. More than 105 leading clinical trial centers in eight countries in North America and Europe participated in the study.

·       The primary efficacy endpoint, overall survival (OS) in the intention-to-treat population of 343 patients had a hazard ratio (HR) = 0.94 and was not statistically significant.

·       In the 194 patients with recurrent grade 3 IDH mutant astrocytoma, clinically meaningful improvements in both OS and PFS were observed.

·       Median OS in the eflornithine + lomustine arm was 34.9 months compared to 23.5 months in the lomustine alone arm with HR = 0.64 (log rank p = 0.016).

·       PFS showed a correlating benefit with median PFS of 15.8 months in the eflornithine + lomustine arm and 7.2 months in the lomustine alone arm with HR = 0.58 (log rank p = 0.015).

·       The combination of eflornithine and lomustine was generally well-tolerated. The known side effect profile of eflornithine combined with lomustine was consistent with data from earlier studies and showed no unexpected safety signals.  The most common Grade 3+ treatment emergent adverse events of relevance were related to myelosuppression and hearing impairment. Similarly, the proportion of patients with Grade 3+ hematology parameters and those with Grade 3 + clinical chemistry parameters were as expected.

“The subset results for the patients with recurrent grade 3 astrocytoma in the STELLAR study represent the first positive outcome to show significant increases in overall survival and progression free survival in a very difficult-to-treat form of malignant glioma,” said Howard Colman, MD, PhD, FAAN, the Jon M. Huntsman Presidential Chair in Neuro-Oncology at the Huntsman Cancer Institute at the University of Utah.  “These findings from the STELLAR study are very impressive and provide caregivers and patients with hope for a new treatment option for this fatal disease.”

The results from the Phase 3 STELLAR study will be presented at an upcoming medical conference.

About Eflornithine

Eflornithine is a novel cytostatic agent that irreversibly inhibits ornithine decarboxylase, a key enzyme in mammalian polyamine biosynthesis that is upregulated in certain types of cancer.

Eflornithine has been granted Orphan Drug Designation and Breakthrough Therapy Designation for the treatment of patients with anaplastic glioma by the U.S. Food and Drug Administration (FDA) and has also been granted Orphan Medicinal Product status for the treatment of glioma by the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA).

About Orbus Therapeutics

Orbus Therapeutics Inc. is a late-stage, private biopharmaceutical company that is dedicated to developing products that treat rare diseases for which there are few, if any, effective therapies. The Company’s lead product candidate, eflornithine, is being evaluated in a pivotal Phase 3 clinical trial in patients with recurrent anaplastic astrocytoma, a rare form of central nervous system cancer. For more information, please visit the Company's website at http://www.orbustherapeutics.com