FDA Grants Fast Track Designation to BST-236 for Older Adults With Acute Myeloid Leukemia

The FDA has granted a Fast Track designation to BST-236 (aspcytarabine) for the treatment of patients with acute myeloid leukemia (AML) who are 75 years or older or have comorbidities that preclude the use of intensive induction chemotherapy, Biosight Limited announced in a press release.

BST-236 is under evaluation in a phase 1/2a clinical trial (NCT02544438) as a single-agent for the frontline treatment of patients with AML who are unfit for standard chemotherapy. A phase 2 clinical trial (NCT03435848) is also underway with plans to begin in the fourth quarter of 2020, evaluating BST-236 as treatment of patients with relapsed/refractory myelodysplastic syndrome (MDS) and AML.

“Receiving Fast Track designation from the FDA is an important recognition of the potential of BST-236 to address the significant unmet need in the population of AML patients who are medically unfit to receive intensive chemotherapy, and to improve the outcomes for these patients” said Ruth Ben Yakar, PhD, chief executive officer of Biosight, in a statement. “The compelling safety and efficacy data from both a completed Phase 1/2a and ongoing Phase 2b studies of BST-236, may establish it as a new intensive therapy backbone of AML and may, for the first time, allow older adults deemed unfit for standard chemotherapy, to benefit from an intensive treatment.”

BST-236, a novel proprietary anti-metabolite, is composed to cytarabine that is covalently bound to asparagine to act as a pro-drug of cytarabine. For over 40 years, cytarabine has served as the backbone of AML therapy because of its superior efficacy. Unfortunately, it is associated with severe bone marrow, gastrointestinal, and neurological toxicities that limit its use in certain patients, such as those who are older or medically compromised.

This novel agent is designed to enable high-dose therapy with lower systemic exposure in order to free cytarabine and relative sparing of normal tissues, so the agent may be a superior therapy for the treatment of patients with AML and other hematologic malignancies, including older patients who are unfit for intensive therapy.

The phase 2B trial remains ongoing to confirm the results of the phase 1/2a trial. The trial is an open-label, single-arm, single-agent, multicenter study of adult patients with newly diagnosed AML who have been deemed unfit for standard therapy. The patients will receive up to 4 cycles of 6-day treatments with BST0236 given intravenously, including 1 or 2 induction courses followed by 1 to 2 consolidation courses of treatment.

The primary end point of the study is complete response. To be included in the trial, patients must not be eligible for standard induction chemotherapy, have creatinine clearance ≥45 mL/min, liver enzymes ≤2.5 times the upper limits of normal (ULN), and total bilirubin ≤1 x ULN. Patients must also have an ECOG performance status of ≤ 2. Patients with relapsed or refractory disease, acute promyelocytic leukemia, a previous treatment for AML, or a history of myeloproliferative neoplasms are excluded from the study.

The phase 1/2a open-label, uncontrolled study was aimed to evaluate the safety and efficacy of the single agent as treatment of patients with relapsed or refractory AML or acute lymphoblastic leukemia. Patients were gradually enrolled into 4 subsequent cohorts of escalating study doses, which ranged from 0.5 gr/m2 to 6 gr/m2. The primary end point of the study was maximum tolerated dose and dose-limiting toxicities, while secondary end points including safety and tolerability, pharmacokinetics, and response rate.

Patients were eligible to enroll if they had relapsed/refractory disease and an ECOG performance status of ≤ 2. Patients with uncontrolled intercurrent illnesses, compromised pulmonary function requiring oxygen therapy, and any other significant concurrent diseases were ineligible to enroll.

BST-236 was previously granted an Orphan Drug designation by the FDA for the potential treatment of patients with AML.

_Reference:

_{Biosight Granted U.S. FDA Fast Track Designation for BST-236 for the Treatment of Acute Myeloid Leukemia. News Release. August 4, 2020. Accessed August 4, 2020. https://bit.ly/2DikxO1}