FDA Grants Rare Pediatric Disease Status to AML Therapy OXi-4503

FDA Grants Rare Pediatric Disease Status to AML Therapy OXi-4503

The U.S. Food and Drug Administration (FDA) has granted its Rare Pediatric Disease designation to Mateon Therapeutics’ OXi-4503 (combretastatin A1-diphosphate, CA1P) for the treatment of children and teens with acute myeloid leukemia (AML) who carry genetic mutations that disproportionately affect this patient population.

AML accounts for 15% of all acute leukemia cases in children and has a worse prognosis than other forms of leukemias, especially for those who carry specific mutations and who have poor outcomes even after multiple therapies and stem cell transplantation. 

New therapies are needed for pediatric patients with AML since about one-third of these children relapse after initial chemotherapy treatment.

A recent Phase 1B clinical trial showed OXi4503, in combination with standard chemotherapy cytarabine, was well-tolerated in adults with AML, and a maximum dose was identified for further clinical development. 

Of the 26 patients who were evaluated, four achieved complete remission — when all signs and symptoms of cancer have disappeared — and one a partial remission. For those patients who achieved a complete remission, the median survival time was roughly 1.4 years, which was significantly longer than the remaining patients who did not reach complete remission. 

Additionally, four of the five patients who responded were 65 years or older and had adverse genetic mutations. 

OXi4503 has a dual mechanism of action of directly killing cancer cells and making the tumor cells vulnerable to chemotherapy.

As a single therapy, OXi4503 demonstrated anti-leukemic activity in animal models of AML. In combination with cytarabine, it was more effective than either medicine alone in a xenografted human AML model, in which cancer tissue is transplanted into animals for testing. 

These findings supported a Phase 1 dose-finding study (NCT00977210) in patients with advanced solid tumors and a Phase 1A trial (NCT01085656) designed to evaluate the safety profile and maximum tolerable dose for further Phase 2 trials in relapsed AML patients or those who failed to respond to other therapies. Here, as a single agent, there were signs of anti-AML activity.

The FDA grants its rare pediatric disease designation to potential therapies for diseases with serious outcomes that affect fewer than 200,000 people between birth and 18 years of age. Sponsors who received approval for a new medicine application to prevent or treat rare diseases in children may be eligible for a voucher that can be redeemed to obtain priority review of any further marketing applications. 

Along with OXi4503, Mateon also has rare pediatric disease designations for the anticancer combretastatin A-4 phosphate (CA4P), an alternative form of OXi4503, to treat diffuse intrinsic pontine glioma and melanoma.

“We are excited about this Rare Pediatric Disease designation for AML,” Vuong Trieu, PhD, CEO of Mateon, said in a press release. “This builds on our previous Rare Pediatric Disease designations for OT-101 and CA4P.”

“It also completed our refocusing of the company to rare pediatric diseases. We are looking forward to initiate clinical programs among these indications post-COVID-19,” he added.