Sunesis Pharmaceuticals Announces Presentation of Results from Completed Phase 1A Healthy Volunteer Study Evaluating Oral Non-Covalent BTK inhibitor SNS-062 at ASH Annual Meeting
Program On Track to Begin Dosing in Phase 1B/2 Study of Patients with B-Cell Malignancies in the First Half of 2017
“These final results from the Phase 1A Healthy Volunteer study suggest that SNS-062, with a favorable safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile, and its improved PK properties over ibrutinib and acalabrutinib, has significant potential to become a new treatment option for patients with B-cell malignancies,” said
“The safety profile, extent of SNS-062 exposure, and duration of BTK inhibition from these study results are encouraging and support our plans for a Phase 1B/2 study to assess safety and efficacy in patients with advanced B-cell malignancies after prior ibrutinib exposure, both with and without a BTK C481 mutation,” said Daniel Swisher, President and Chief Executive Officer of Sunesis. “We are preparing an IND filing for this year as we work closely with our identified clinical sites for this study, and expect to begin dosing patients within the first half of 2017.”
The reported data from this Phase 1A randomized, double-blind, placebo-controlled, single-dose study are from four sequential cohorts of 8 subjects each who were randomly assigned to receive progressively higher single oral administrations of SNS-062 at doses of 25, 50, 100, 200, and 300 mg (n=6 per cohort) or placebo (n=2 per cohort).
For the primary endpoint of safety in stage 1, investigators were blinded to treatment arm for assessment of relatedness. Overall, AEs were reported for 8 (33%) subjects who received SNS-062 and for 3 (38%) subjects who received placebo. In the unblinded stages 2 and 3 of the trial, a similar pattern and rate of AEs were observed. Overall, no obvious pattern of dose-dependent toxicity was observed. All AEs were transient and low grade. None of the AEs, laboratory abnormalities, or ECG or telemetry findings were considered clinically meaningful. No SAEs were reported.
SNS-062 was rapidly absorbed and had mean plasma half-life values across all dose cohorts of 6.9 to 17 hours. SNS-062 demonstrated rapid, profound (~100%), and prolonged inhibition of BTK at all dose levels support investigation of a twice-daily dosing regimen in B-cell malignancies with or without an acquired BTK resistance mutation.
Furthermore in stage 2, food had no impact on the extent of absorption or elimination of SNS-062, suggesting that it may be administered to patients without regard to food. In stage 3, SNS-062, similar to ibrutinib, is a sensitive substrate of CYP3A4 and administration with moderate/strong CYP3A4 inhibitors or inducers is not recommended.
SNS-062 is a novel, second-generation BTK inhibitor, a class of kinase inhibitors that selectively inhibits the enzyme Bruton's tyrosine kinase (BTK). This target mediates signaling through the B-cell receptor, which is critical for adhesion, migration, proliferation and survival of normal and malignant B-lineage lymphoid cells. Unlike other drugs in its class, SNS-062 binds non-covalently and reversibly to the BTK enzyme. Its binding profile along with improved PK/PD properties potentially provide SNS-062 an opportunity to address the leading acquired resistance to ibrutinib, a mutation in the enzyme’s binding site required for covalent binding. In preclinical studies, SNS-062 demonstrated potent activity against C481S mutated B-cell malignancies, and has been studied in healthy subjects in a completed Phase 1A, randomized, double-blind, placebo-controlled dose-ranging study to investigate the drug’s safety, pharmacokinetics, and pharmacodynamics. With the reported successful study outcome, SNS-062 is proceeding to a Phase 1B/2 study in patients with B-cell malignancies.
Sunesis is a biopharmaceutical company focused on the development and commercialization of new oncology therapeutics for the potential treatment of solid and hematologic cancers. Sunesis has built a highly experienced cancer drug development organization committed to improving the lives of people with cancer. Currently, the company is focused on pursuing regulatory approval in
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