Oncorena announced today that the U.S. Food and Drug Administration (FDA) has approved the company's Investigational New Drug (IND) application for ONC175, allowing the initiation of clinical studies in the United States. The approval enables Oncorena to expand its ongoing Phase I/II trial, Oncorella-1, which is evaluating the safety, tolerability, and anti-tumor efficacy of orellanine in patients with metastatic clear-cell or papillary renal cell carcinoma.
The Oncorella-1 study (NCT05287945, ONC001-CL-001) is designed as an open-label, single-arm trial that will enroll up to 75 patients with severe metastatic renal cancer who require dialysis. These patients represent a population with particularly high unmet medical need, having exhausted available treatment options.
"This approval brings us closer to being able to evaluate the potential for this novel treatment in patients in desperate need for new and better options," said Börje Haraldsson, M.D., Ph.D., CEO and co-founder of Oncorena. "We are excited to start the first US site, MD Anderson in Houston, Texas, where the study will be led by investigator Professor Nizar Tannir, a world-leading expert in renal cancer."
The trial is currently ongoing at Karolinska University Hospital in Stockholm, Sweden, and will now expand to include MD Anderson Cancer Center as its first U.S. site.
A Unique Mechanism of Action
ONC175 represents a potentially groundbreaking approach to treating metastatic renal cell carcinoma. The investigational drug contains synthetically produced orellanine as its active ingredient, a compound known for its high specificity to kidney tissue. Orellanine's mechanism of action involves inducing irreversible renal failure, but importantly, clinical evidence has established that it does not affect organs other than the kidneys.
This kidney-specific activity makes ONC175 particularly suitable for patients who already require dialysis due to kidney failure, eliminating the primary concern about orellanine's renal toxicity. Preclinical studies have demonstrated that ONC175 has a powerful and highly organ-specific mode of action capable of eradicating human metastatic renal cancer cells.
The primary goal of Oncorena's development program is to establish ONC175 as a potential curative treatment for metastatic renal cell carcinoma specifically in patients with no remaining kidney function who are dependent on dialysis.
Addressing a Significant Unmet Need
According to the World Health Organization, approximately 400,000 patients globally are affected by kidney cancer. While early-stage kidney cancer can often be cured through surgical intervention, the prognosis becomes significantly less favorable once the disease has metastasized.
Current treatment approaches for metastatic renal cell carcinoma include various targeted therapies and immunotherapies. However, these treatments rarely result in complete cures, highlighting the substantial unmet medical need for new, effective, and safe therapeutic options.
The Oncorella-1 trial represents a significant step forward in exploring innovative approaches to treating this challenging disease, particularly for patients who have progressed through standard therapies and face limited options.
Trial Design and Next Steps
As an open-label, single-arm study, Oncorella-1 will focus on establishing the safety profile of ONC175 while also gathering preliminary efficacy data. The trial's expansion to the United States marks an important milestone in the development program, potentially accelerating patient recruitment and broadening the study's geographical reach.
Professor Nizar Tannir, who will lead the trial at MD Anderson Cancer Center, brings significant expertise in renal cancer research and treatment, further strengthening the study's scientific foundation.
Oncorena's approach represents a novel paradigm in oncology drug development, leveraging a compound's organ specificity to create a therapeutic window in a carefully selected patient population. If successful, this strategy could provide a template for developing other highly targeted cancer therapies that exploit unique biological vulnerabilities.
