On January 18, 2024 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs reported the publication of clinical data from studies of CPP-1X (also known as α-Difluoromethylornithine (DFMO) or Eflornithine) in neuroblastoma (Press release, Panbela Therapeutics, JAN 18, 2024, View Source [SID1234639332]). According to Hogarty et al, children with relapsed refractory neuroblastoma have dismal outcomes and new therapeutic options are needed. Data published in the British Journal of Cancer investigated the tolerability and activity of depleting polyamines by high dose CPP-1X and celecoxib in combination with standard of care chemotherapy in heavily pretreated neuroblastoma patients. Results showed that DFMO treatment was well tolerated, and the median time-to-progression was 19.8 months. The work reflects the Company’s previous collaboration with New Advances in Neuroblastoma Therapy Consortium (NANT) (View Source). A link to the publication can be found here: View Source

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From the Phase 1 dose range finding study of CPP-1X in heavily pretreated neuroblastoma patients, CPP-1X was well tolerated. The best overall response included 2 partial responses (PR), 4 minor responses (MR), 10 Stable disease (SD), 7 progressive disease (PD) and 1 unevaluable. All patients with an overall response of PR or MR sustained this response until stopping or completing protocol therapy. The overall objective response rate (CR+PR) was 9% and rate of any response (CR+PR+MR) was 26%. At 2 years, PFS (progression free survival) for the entire cohort was 29.5%. Notably, three patients completed protocol therapy and remain without disease progression or event at >4 years from treatment end in the absence of additional therapy.

These results build upon the recent FDA approval of CPP-1X or DFMO to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB) who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. Results from these studies suggest that CPP-1X is a safe, oral treatment option that may improve response rates in heavily pretreated relapsed refractory neuroblastoma patients and are the basis for the ongoing ANBL-1821 Phase 2 trial.

"We are excited about the publication of these Phase 1 trial results in light of the recent DFMO FDA approval for patients in maintenance therapy. From this dose escalation study, our collaborators were able to demonstrate high dose DFMO is well tolerated and demonstrated activity in patients with heavily pretreated neuroblastoma," said Elizabeth Bruckheimer, PhD, Vice President & Chief Scientific Officer of Panbela. "Moreover, three patients remain alive over four years from treatment end without any additional therapy which suggests that high dose DFMO treatment in combination with chemotherapy may be a potential treatment option for this high unmet need population."

"Overall, these results in addition to the recent approval of DFMO as a maintenance therapy, suggests a role for polyamine inhibition therapy for neuroblastoma that may impact other cancer types such as prostate cancer. We are excited by these results and the potential role for CPP-1X in the clinical management of neuroblastoma and cancer as a whole." said Dr. Bruckheimer. "These studies were the basis for the ongoing Children’s Oncology Group Phase II trial in relapsed refractory neuroblastoma to support the goal of developing effective novel therapies for patients with unmet medical needs."

First author Michael Hogarty, MD, Professor of Pediatrics at the University of Pennsylvania, and Children’s Hospital of Philadelphia said, "The results from the Phase 1 study have built upon the preclinical work performed in my laboratory demonstrating a role of deep polyamine depletion as a potential therapeutic target for relapsed or refractory neuroblastoma. By understanding the underlying biology and role of MYC signaling and the polyamine pathway in neuroblastoma, we are able to show the potential impact of high-dose DFMO in neuroblastoma."