publication date: Sep. 14, 2018
Drugs & Targets
FDA approves moxetumomab pasudotox-tdfk for hairy cell leukemia
FDA has approved AstraZeneca’s moxetumomab pasudotox-tdfk, a CD22-directed cytotoxin indicated for adult patients with relapsed or refractory hairy cell leukemia who received at least two prior systemic therapies, including treatment with a purine nucleoside analog.
The approval was based on Study 1053 (NCT01829711) in patients with histologically confirmed HCL or HCL variant requiring treatment based on presence of cytopenias or splenomegaly and who had received prior treatment with at least two systemic therapies, including one PNA. Eligible patients had serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60 mL/min as estimated by the Cockcroft Gault equation. A total of 80 patients were enrolled; 77 with classic HCL and 3 with HCL variant. Patients received moxetumomab pasudotox-tdfk, 0.04 mg/kg as an intravenous infusion, over 30 minutes on days 1, 3, and 5 of each 28-day cycle for a maximum of 6 cycles or until documentation of complete response (CR), disease progression, or unacceptable toxicity.
Efficacy in HCL was evaluated by the blinded independent review committee-assessed rate of durable CR confirmed by maintenance of hematologic remission (hemoglobin ≥11 g/dL, neutrophils ≥1500/mm3, and platelets ≥100,000/mm3 without transfusions or growth factor for at least 4 weeks) more than 180 days after IRC-assessed CR. The IRC-assessed durable CR rate was 30 percent (24/80 patients; 95% CI: 20, 41). The IRC-assessed CR rate was 41 percent (33/80 patients; 95% CI 30,53).
The most common non-laboratory adverse reactions (≥20%) of any grade were infusion related reactions, edema, nausea, fatigue, headache, pyrexia, constipation, anemia, and diarrhea. The most common grade 3 or 4 adverse reactions (reported in at least ≥5% of patients) were hypertension, febrile neutropenia, and hemolytic uremic syndrome. Adverse reactions resulting in permanent discontinuation of moxetumomab pasudotox-tdfk occurred in 15 percent (12/80) of patients. The most common adverse reaction leading to discontinuation was HUS (5%). The most common adverse reactions resulting in dose delays, omissions, or interruptions was pyrexia (3.8%).
The recommended dose of moxetumomab pasudotox-tdfk is 0.04 mg/kg administered as a 30-minute intravenous infusion on days 1, 3, and 5 of each 28-day cycle for a maximum of 6 cycles or until occurrence of disease progression or unacceptable toxicity.
Boehringer Ingelheim acquires all ViraTherapeutics shares to develop next-gen viral-based therapies
Boehringer Ingelheim has acquired all shares of ViraTherapeutics, a biopharmaceutical company specializing in the development of oncolytic viral therapies.
ViraTherapeutics developed the lead candidate VSV-GP (Vesicular Stomatitis Virus with modified glycoprotein), which is being investigated alone and in combination with other therapies. The total transaction value of EUR 210 million is based on an option and share purchase agreement signed between the companies in Aug. 2016.
The lead investigational candidate leveraging the platform, VSV-GP, has shown promising results in pre-clinical models, especially in combination with key immune modulatory principles Boehringer Ingelheim is developing.
ViraTherapeutics was a portfolio company of the two venture investors EMBL Ventures and the Boehringer Ingelheim Venture Fund (BIVF).