FDA grants BST-236 Fast Track designation for the treatment of older patients with AML

On August 4, 2020, the U.S. Food and Drug Administration (FDA) granted BST-236 (aspacytarabine) Fast Track designation for the treatment of acute myeloid leukemia (AML) in older patients (≥ 75 years) and in adult patients with comorbidities that make them unsuitable for intensive induction chemotherapy. The decision was based on the encouraging safety and efficacy data of the completed phase I/IIa study (NCT02544438) and the ongoing phase IIb study (NCT03435848).¹ 

Cytarabine has been used as the backbone of AML therapy for over 40 years due to its superior efficacy. However, it is associated with toxicities that significantly limit its use, especially in older and medically compromised patients, therefore, there is a significant unmet need to improve outcomes in these patient groups.

BST-236 (aspacytarabine) consists of cytarabine covalently bound to asparagine and acts as a pro-drug of cytarabine, thereby enabling high-dose therapy with lower systemic exposure to free cytarabine, which may help to reduce the toxicities normally associated with cytarabine¹. BST-236 has been previously granted orphan drug designation by the FDA.

Phase I/IIa study (NCT02544438)^3,4

• Start/end: September 2015–September 2017
• Open-label, uncontrolled, dose-escalation study to evaluate the safety and efficacy of BST-236 in 26 adult patients with newly diagnosed (ND) or relapsed/refractory AML or acute lymphoblastic leukemia who are older or unfit for intensive therapy
• The median age was 76.5 years, with 84.6% of patients aged ≥ 70 years
• BST-236 was administered intravenously (IV) once daily over 60 minutes for six consecutive days, in six dose-escalating cohorts (range, 0.3–6 g/m² per day)

Results⁴

• Maximum tolerated dose: 6 g/m² per day
•  BST-236 treatment was well tolerated
  • Grade 3 or higher treatment-emergent adverse events were mainly hematological or infection-related, such as febrile neutropenia (23%), pneumonia (20%), anemia (19%), thrombocytopenia (12%), and neutropenia (35%)
• 30-day mortality was 30.7%
• Overall response rate was 29.6%
  • A higher ORR (45.5%) was seen in the subgroup analysis for ND patients with AML, de novo, or secondary to myelodysplastic syndrome and unfit for standard induction
• Median overall survival was 2.8 months in the entire population, 6.5 months in ND patients, and was not reached at 20 months in patients achieving complete remission

Phase IIb study (NCT03435848)⁵

• Open-label, single arm, multicenter study to assess the efficacy and safety of BST-236 as a single agent in adults with ND AML who are not eligible for standard induction therapy due to advanced age or comorbidities
• Estimated to enroll 65 patients
• BTS-236 dosage:  4.5 g/m² per day or 2.5 g/m² per day, IV, for six days, with up to four courses of treatment (≤ two induction courses followed by ≤ two consolidation courses)
• Study participation: 52 weeks, including treatment and follow-up periods

Primary outcome: Complete remission