On September 16, 2020 Mateon Therapeutics "Mateon" (OTCQB: MATN), a leading developer of TGF-β therapeutics for oncology and COVID-19, reported that the US Food and Drug Administration (FDA) granted our request and designate OXi4503 (combretastatin A1-diphosphate; CA1P) for treatment of acute myeloid leukemia (AML) due to genetic mutations that disproportionately affect pediatric patients as a drug for a "rare pediatric disease," as defined in section 529(a)(3) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360ff(a)(3)) (Press release, Mateon Therapeutics, SEP 16, 2020, View Source [SID1234565247]).
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"We are excited about this Rare Pediatric Disease designation for AML.", said Dr. Vuong Trieu, Chief Executive Officer of Mateon. "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. In the meantime, we are focusing on deploying OT-101 against severe COVID-19 and Artemisinin against COVID-19 in general among various clinical trials globally.".
OXi4503 in combination with standard chemotherapy drug cytarabine was generally well tolerated by adult AML patients and a maximum tolerated dose level of OXi4503 was identified as the recommended dose for further clinical development of this novel two-drug combination. In 26 evaluable AML patients, there were 4 complete remissions (CR/CRi) and one partial remission (PR). The CR responses were associated with >1-year overall survival times. The combination therapy exhibited a manageable toxicity and a promising benefit to risk profile in older adults with relapsed AML. Four of the 5 objective responders were in the ≥65-years poor prognosis age category with adverse cytogenetic features.
Acute leukemia is the most common cancer in children accounting for one-third of all childhood cancers. Acute lymphoblastic leukemia (ALL) accounts for 80% and acute myeloid leukemia (AML) accounts for 15% of all acute leukemia cases in children. Children with AML have a worse prognosis with a 5-year survival rate of 64% than children with ALL who have a 5-year survival rate of ~90% on contemporary risk-adjusted treatment programs. Children with AML who have unfavorable risk factors, such as adverse cytogenetics, have a particularly poor survival outcome even after intensive multimodality therapy and hematopoietic stem cell transplantation. Approximately one-third of children with AML relapse after induction chemotherapy and only one-third of these patients become long-term survivors. Relapsed disease is the greatest challenge to a better survival outcome in AML. Although new drugs have recently been developed against several molecular targets in AML blast cells, the vast majority of relapsed pediatric AML patients still die of leukemia. Therefore, novel therapies are urgently needed for pediatric AML.
About Oxi4503
OXi4503 exhibited single-agent anti-leukemia activity in animal models of AML and in a Phase 1A clinical study for relapsed/refractory (R/R) AML. Notably, the combination of OXi4503 with cytarabine (ARA-C) in xenografted human AML models was more effective than either drug alone. The clinical safety profile of OXi4503 as a single agent has previously been evaluated in Phase 1A clinical trials. In the NCT00977210 Phase 1 dose-finding study in 43 advanced solid tumor patients, OXi4503 doses were escalated from 0.06 to 15.4 mg/m2, and 8.5 mg/m2 was defined as the maximum tolerated dose (MTD). In the NCT01085656 Phase 1A trial designed to evaluate the safety profile, MTD, and recommended Phase 2 dose of OXi4503 in patients with R/RAML and MDS, a total of 18 patients were treated with single-agent OXi4503 and showed a manageable safety profile at single-agent dose levels up to of 7.81 mg/m2 and there was early evidence of possible single-agent anti-AML activity. More recently, a Phase 1B study was performed to evaluate the safety, tolerability, and clinical activity of a combination of OXi4503 and the standard anti-AML drug ARA-C. The combination therapy exhibited a manageable toxicity and a promising benefit to risk profile in adults with relapsed AML. An MTD level of OXi4503 was identified as the recommended dose for further clinical development of this novel two-drug combination. In 26 evaluable AML patients, there were four complete remissions (CR/CRi) and one partial remission. The median overall survival time for the four patients who achieved a CR/CRi was 528 days (95% confidence interval [CI]: 434 – NA), which was significantly longer than the median overall survival time of 113 days (95% CI: 77–172) for the remaining 22 patients who did not achieve a CR (Log rank Chi-square = 11.8, P-value = 0.0006).
About rare pediatric disease voucher program
The FDA grants rare pediatric disease designation for diseases with serious or life-threatening manifestations that primarily affect people aged from birth to 18 years, and that affect fewer than 200,000 people in the U.S. Under the FDA’s Rare Pediatric Disease Priority Review Voucher program, a sponsor who receives an approval of a new drug application or biologics license application for a product for the prevention or treatment of a rare pediatric disease may be eligible for a voucher, which can be redeemed to obtain priority review for any subsequent marketing application, and may be sold or transferred. In August 2019, AstraZeneca has reportedly paid approximately $95 million to buy a priority review voucher from Swedish Orphan Biovitrum (Sobi) (View Source). Likewise, Biohaven Pharmaceutical Holding Company Ltd. reportedly paid approximately $105 million for a priority review voucher in March 2019 (View Source).