Biosight‘s BST-236 (aspacytarabine), a less toxic form of chemotherapy for acute myeloid leukemia (AML), has received fast track designation from the U.S. Food and Drug Administration (FDA) for patients ages 75 and older, and for those unfit to receive intensive chemotherapy as an initial treatment, the company announced in a press release.
A therapy candidate is placed on the fast track program if the FDA determines it might treat a serious condition with unmet clinical need. Fast track status is usually awarded either because no treatments are currently available or the potential therapy offers significant benefits over approved alternatives.
The designation is meant to speed the development and review of BST-236, facilitating discussions with the FDA and enabling the therapy to qualify for priority review and accelerated approval. Both are designed to get treatments to patients more quickly, provided that certain criteria are met. BST-236 also has been named an orphan drug by the FDA because it treats a rare disease or condition.
“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, CEO of Biosight.
AML treatment typically starts with an intensive course of chemotherapy to induce remission. That is followed by a consolidation regimen that destroys any remaining leukemia cells and helps prevent a relapse.
The chemotherapy cytarabine has served as the backbone of both induction and consolidation treatments for over four decades due to its superior efficacy. But the therapy is associated with severe side effects, including brain toxicity, bone marrow suppression — or the inability to produce blood cells — and infections. These side effects lead to a high rate of treatment-related deaths.
Thus, cytarabine is not indicated for older patients and those with associated diseases, who are most susceptible to its adverse events. The outcomes of these patients remain poor, despite the approval of new therapies.
BST-236 is a new pro-drug of cytarabine that enables the delivery of high cytarabine doses to leukemia patients without the severe adverse events of the therapy.
Simply put, BST-236 is made of cytarabine that’s bound to the amino acid asparagine, which gradually releases free cytarabine after being infused. The metabolism of this pro-drug is distinct from that of cytarabine, avoiding the cytarabine peak exposure that causes most of its side effects.
The less-toxic chemotherapy was investigated in a dose-escalation Phase 1/2 trial (NCT02544438), both as an initial treatment and after prior therapies. The participants all were AML patients who were unfit for standard induction therapy. To determine the safest and most effective dose, the participants received daily doses of cytarabine ranging from 0.3 to 6 g/m2. The selected dose was 4.5 g/m2 per day, which contains about 3 g/m2 of cytarabine.
After promising results, an ongoing Phase 2b trial (NCT03435848) was launched to continue assessing BST-236 as a potential treatment for newly diagnosed AML patients. The ELPIS trial is recruiting at 16 sites in the U.S. and Israel and will continue to investigate the selected dose in 65 patients not eligible for standard induction regimens, either due to older age (75 years or higher) or to the presence of additional heart or lung diseases.
Results presented late last year, at the 2019 American Society of Hematology Annual Meeting, demonstrated that BST-236 is safe and well tolerated in these patients, and leads to high response rates and prolonged survival.
The findings included data from 21 newly diagnosed AML patients who received BST-236 as part of the Phase 1/2 trial or the ELPIS trial. These individuals had a median age of 76, and most (67%) had AML secondary to therapy or myelodysplastic syndrome, a precursor condition.
While all of the patients had a poor prognosis, only 7% of those receiving daily doses of 4.5 g/m2 or higher died within the first 30 days. Moreover, 36% attained a complete response to treatment, taking a median of 27 days to fully recover their normal blood cell levels. Some of the individuals with complete responses had been previously been given multiple courses of hypomethylating agents (HMA).
“The accumulating clinical data suggest that aspacytarabine is safe and efficacious for the treatment of AML patients who are unfit for standard induction therapy, including patients with prior exposure to HMA, which may establish aspacytarabine as a new therapeutic backbone for AML, either as a single agent or in combination with targeted therapy,” the researchers wrote.
“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,” Yakar added.