VONJO contains pacritinib citrate. Pacritinib is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. MF is often associated with dysregulated JAK2 signaling. Pacritinib has higher inhibitory activity for JAK2 compared to JAK3 and TYK2. At clinically relevant concentrations, pacritinib does not inhibit JAK1. Pacritinib exhibits inhibitory activity against additional cellular kinases (such as CSF1R and IRAK1) the clinical relevance of which is unknown.It is a citrate salt.
Appl. No. N208712 Applicant Holder: CTI BIOPHARMA CORP
News released on Mar 6, 2023:
CTI BioPharma Reports Fourth Quarter and Full Year 2022 Financial Results
Highlights:
- FDA approval of VONJO (pacritinib) for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L.
- $54 million in net sales in the first nine months following VONJO launch.
- Over 1,000 patients commercially treated with VONJO in 2022.
- Inclusion in the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms, with a recommendation for VONJO as a: First-line treatment option for higher-risk myelofibrosis patients with platelet counts
INDICATIONS AND USAGE: treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) with a platelet count below 50 × 109/L.
DOSAGE AND ADMINISTRATION: 200 mg / 100 mg orally twice daily; taken with or without food.
Monitoring for Safety is important e.g. CBC, coagulation testing, ECG, prior to and during the treatment.
ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
Hemorrhage
Diarrhea
Thrombocytopenia
Prolonged QT Interval
Major Adverse Cardiac Events
Thrombosis
Secondary Malignancies
Risk of Infection
Dose Modification is needed for Adverse Reactions such as diarrhea, thrombocytopenia, hemorrhage, and prolonged QT interval.
API
Slightly or not soluble in water.
COMPOSITION / EXCIPIENTS
VONJO capsule is for oral administration. Each capsule contains 100 mg of pacritinib equivalent to 140.65 mg of pacritinib citrate and the inactive ingredients are microcrystalline cellulose NF, polyethylene glycol 8000 (PEG 8000) NF, and magnesium stearate NF. The gelatin capsule is bovine derived. The capsule shell contains gelatin, titanium dioxide, black iron oxide, erythrosine, red iron oxide, and printing ink containing shellac, propylene glycol, titanium dioxide, sodium hydroxide, and povidone.
PD
Pacritinib inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5) protein in a dose-dependent manner (ex vivo) in expanded erythroid progenitor cells derived from healthy subjects.
PK
Pharmacokinetics of pacritinib increases in a less than dose-proportional manner. VONJO 200 mg twice daily accumulates 386% and reaches steady-state within a week.
Tmax: 4-5 h.
Food Effect: no siginificant effect. (200 mg with a high fat meal)
Plasma Protein Binding: 98.8%
Metabolism: CYP3A4 isozyme, metabolite - M1 and M2.
Half-life: 27.7 h
Excretion: Following a single oral administration of radiolabeled pacritinib 400 mg in healthy adult subjects, 87% of the radioactivity was recovered in feces, and 6% was recovered in urine. No unchanged drug was excreted in feces and 0.12% of unchanged drug was excreted in urine.
ORANGE BOOK PATENTS
8153632 (EXP 01/17/2029) - a chemical
8980873 (EXP 03/25/2030) - a crystal structure (X-ray diffraction peak)
9573964 (EXP 05/05/2028) - a method of treating a condition
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