On September 29, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that data from a bioequivalence study for GFH009, its potent, highly selective, clinical-stage small molecule that inhibits cyclin-dependent kinase 9 (CDK9) (Press release, Sellas Life Sciences, SEP 29, 2022, View Source [SID1234621560]). In the ongoing Phase 1 clinical trial of GFH009 monotherapy in patients with relapsed/refractory hematologic conditions, including acute myeloid leukemia and lymphoma, GFH009 is administered intravenously as a solution. The bioequivalence study was performed to evaluate the effect of different formulations on GFH009’s preclinical pharmacokinetic (PK) profile. Dr. Dragan Cicic, MD, Senior Vice President, Clinical Development, of SELLAS, presented the findings at this year’s Meeting of the Society of Hematologic Oncology (SOHO) in a poster titled "Pharmacokinetics and Bioequivalence of Two Formulations of GFH009 Maleate Injection in Sprague Dawley Rats."
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The solution for GFH009 was originally developed with the pH of 4.5 (acidic). Human blood has a physiological pH of around 7.35 to 7.45. The closer a drug is to this physiological state, the less acidic and irritating it is for patients. In a four-week rat study, GFH009 was tested at 2.0 mg/kg, 4.0 mg/kg and 8.0 mg/kg. At 4.0 mg/kg, drug exposure approached efficacy, which formed the rationale for the dose selection for the presented PK study. Rats were randomly assigned to group one (pH 4.5) or group two (pH 6.0) and matched by sex and body weight. Each rat received a single dose of GFH009 (4.0 mg/kg) at pH 4.5 or pH 6.0 intravenously in the tail vein at a volume of 5.0 mL/kg. The PK profiles of both GFH009 formulations (pH 4.5 and pH 6.0) were found to be comparable, supporting the application of the pH 6.0 formulation in the ongoing Phase 1 clinical trial.
"At pH 6.0, GFH009 is closer to the physiological pH – thus, it is less acidic – and the drug’s behavior remains comparable to that at pH 4.5," said Dr. Cicic. "As a result, this study allowed us to explore a range of dosing strategies for patients, which helped with dose preparation and administration. The improved formulation also decreased the potential for the infusion reaction and made dosing more well-tolerated after multiple doses or long-time infusion."