BioSight Ltd, a pharmaceutical development company, focused on the development of targeted oncology drugs, reports positive final results in a phase I/II multi-center, open label, dose-escalating study of its lead product BST-236, a novel cytarabine pro-drug, as a single agent for induction therapy in acute leukaemia patients.
The results, presented at the 59th Annual American Society of Hematology Meeting and Exposition by Dr. Tsila Zuckerman of the Rambam Healthcare Center, demonstrated safety and efficacy of BST-236 as a single agent in treatment of newly-diagnosed acute leukemia patients, unfit for standard induction therapy.
The study enrolled 26 acute leukemia patients, including 10 relapsed/refractory acute myelocytic leukaemia (AML) patients and 16 newly-diagnosed older patients unfit for standard induction therapy (median age 78, range 70-90). Of the newly-diagnosed patients, 3 were diagnosed with de novo AML, 8 with AML secondary to myelodysplastic syndrome (MDS), the majority of them progressed to AML while under hypomethylating agent treatment, 3 with AML secondary to myeloproliferative neoplasms, and 2 were newly-diagnosed with acute lymphoblastic leukemia (ALL).
BST-236 was safe and well tolerated at all doses. The maximal dose explored was 6 g/m²/d, the molar equivalent of 4.1 g/m²/d of cytarabine. BST-236 was administrated as a 1-hour infusion for 6 consecutive days. Adverse events included mainly “on-target” hematological events and related infections. No cerebellar toxicity, no mucositis, no renal failure, and no alopecia events were reported.
Forty-five percent of the newly diagnosed AML patients (de novo and secondary to MDS) responded to BST-236, and 36% reached a durable complete remission (CR) after 1 or 2 induction courses. The median age of the responding patients was 80 years, 60% of them had secondary AML, 40% of responders were azacitidine resistant, and 60% and 40% had adverse or intermediate ELN score, respectively. In addition, 1 of the 2 ALL patients, a 90-year old man, reached a durable CR.
All CRs were durable, accompanied by survival of 6.5 to currently 20 months (median not reached). The median overall survival of the entire subgroup of newly-diagnosed AML (responders and non-responders) was 6.5 months, with a 27% 1-year survival rate.
Based on these encouraging results, BioSight intends to launch a multi-center phase IIb study in the US and Israel in the coming months. The study will enroll 65 newly-diagnosed AML patients, age =75 or with comorbidities, who are unfit for standard induction therapy.
Dr. Ruth Ben Yakar, BioSight's chief executive officer said: "We are very excited with the results achieved in the BST-236 phase I/II study. We are especially encouraged by the good safety and efficacy of BST-236 in older and unfit patients with poor baseline characteristics and prognosis. BST-236 activity was demonstrated to be targeted, enabling safe delivery of high cytarabine doses to older patients, up to 90 years old, achieving approximately 3-fold higher response rates compared to currently available treatments. Importantly, the remissions were durable, correlating with significantly prolonged survival. We intend to launch a multi-center phase IIb study in the coming months to confirm these encouraging results”.