CNS Pharmaceuticals, Inc. announced topline results from its pivotal clinical trial evaluating Berubicin in patients with recurrent Glioblastoma Multiforme (GBM) who have failed primary treatment. The randomized, controlled study compared Berubicin to Lomustine, a current standard of care, in 252 patients with a 2:1 randomization favoring the investigational drug.
Trial Design and Patient Population
The clinical trial enrolled patients with Glioblastoma Multiforme who had failed first-line therapy. Patients receiving Berubicin were administered a 2-hour intravenous infusion of 7.5 mg/m² berubicin hydrochloride daily for three consecutive days followed by 18 days off, creating a 21-day treatment cycle. The control arm received Lomustine administered orally once every six weeks.
The study design included a pre-planned, non-binding interim futility analysis conducted by an independent Data Safety Monitoring Board (DSMB). The DSMB's charter mandated review of the primary endpoint, overall survival, as well as secondary endpoints and safety data to determine whether the efficacy data and risk-benefit profile warranted modification or discontinuation of the study.
Clinical Results and Regulatory Milestone
On December 18, 2023, CNS released the DSMB's recommendation to continue the study without modification, indicating acceptable safety and potential efficacy signals at the interim analysis. The recently released topline data from March 25, 2025, showed that while Berubicin produced clinically relevant outcomes that appear comparable to Lomustine across multiple endpoints, it did not demonstrate a statistically significant difference in overall survival, the primary endpoint.
Overall survival represents a rigorous endpoint that the FDA has recognized as a basis for approval of oncology drugs when a statistically significant improvement can be shown relative to a randomized control arm. The trial was not powered to determine non-inferiority between the two treatments.
Drug Development Background
Berubicin is an anthracycline discovered at The University of Texas M.D. Anderson Cancer Center by Dr. Waldemar Priebe, the company's founder. The drug represents the first anthracycline that appears to cross the blood-brain barrier in significant concentrations targeting brain cancer cells, based on clinical and preclinical data.
CNS Pharmaceuticals obtained rights to Berubicin through a series of transactions, initially licensing from Reata Pharmaceuticals, which had allowed their Investigational New Drug application with the FDA to lapse for strategic reasons. On December 17, 2020, CNS announced that its IND application for Berubicin in Glioblastoma Multiforme was in effect, leading to trial initiation in the second quarter of 2021 with the first patient dosed in the third quarter of 2021.
Regulatory Status and Future Plans
Berubicin received Orphan Drug Designation from the FDA on June 10, 2020, for the treatment of malignant gliomas. This designation may enable market exclusivity of seven years from the date of approval of a New Drug Application in the United States, providing important intellectual property protections for the compound.
Given the limited alternative approved therapies for GBM, CNS believes Berubicin has demonstrated potential value as a possible treatment for glioblastoma despite not meeting the primary endpoint. The company is currently evaluating potential paths forward for the program, with any such development planned and executed in consultation with the FDA.
Market Context and Treatment Landscape
Glioblastomas are highly malignant tumors that arise from astrocytes, star-shaped cells making up the supportive tissue of the brain. These tumors reproduce quickly and are supported by large networks of blood vessels, making them particularly challenging to treat. The current treatment landscape for recurrent glioblastoma remains limited, with few effective therapeutic options available to patients who have failed primary treatment.
The company noted that even if Berubicin receives approval, there is no assurance that patients will choose an infusion treatment compared to the current standard of care, which requires oral administration. This consideration highlights the importance of demonstrating clear clinical benefit to justify the more complex administration route.
