OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Pacritinib – Vonjo®

DRUG CLASS

Antineoplastic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Pacritinib	937272-79-2	C28-H32-N4-O3

ANNOTATED BIBLIOGRAPHY

References updated: 28 December 2023

Abbreviations: JAK, Janus kinase; STAT, signal transducer activator of transcription.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of tyrosine kinase inhibitors such as pacritinib).
• DeLeve LD. Erlotinib. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 556.

  (Review of hepatotoxicity of cancer chemotherapeutic agents discusses several tyrosine kinase inhibitors including imatinib, gefitinib, erlotinib and crizotinib, but not pacritinib).
• Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway-targeted therapies: monoclonal antibodies, protein kinase inhibitors, and various small molecules. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1203-36.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2022/208712Orig1s000IntegratedR.pdf

  (FDA review of data on efficacy and safety submitted in support of approval of pacritinib as therapy of myelofibrosis does not provide information of ALT or AST elevations and states that there was no case of serum ALT or AST elevations accompanied by jaundice in the momelotinib treated safety cohort).
• Beauverd Y, McLornan DP, Harrison CN. Pacritinib: a new agent for the management of myelofibrosis? Expert Opin Pharmacother. 2015;16(15):2381–2390. [PubMed: 26389774]

  (Review of the clinical and molecular features of myelofibrosis focusing upon somatic gene mutations and constitutive activation of the Janus kinase [JAK]-signal transducer activator of transcription [STAT] pathways in its pathogenesis which led to the use of JAK1 and JAK2 inhibitors in its management).
• Komrokji RS, Seymour JF, Roberts AW, Wadleigh M, To LB, Scherber R, Turba E, et al. Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Blood. 2015;125:2649–2655. [PMC free article: PMC4490373] [PubMed: 25762180]

  (Among 35 patients with refractory myelofibrosis treated with pacritinib for 6 months, 31% had a clinical response [decrease in splenomegaly] and adverse events included diarrhea [77%], nausea [46%], fatigue [32%], vomiting [31%], abdominal pain [26%], and AST elevations [14% overall, above 5 times ULN in 6%]; no mention of clinically apparent liver injury or jaundice).
• Mesa RA, Vannucchi AM, Mead A, Egyed M, Szoke A, Suvorov A, Jakucs J, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017;4:e225–e236. [PMC free article: PMC8209752] [PubMed: 28336242]

  (Among 327 patients with myelofibrosis treated with pacritinib vs “best available therapy” followed for a median of 23 months, response rates were 19% vs 5% and adverse events rates for anemia and thrombocytopenia were similar in the 2 groups; no mention of ALT elevations or hepatotoxicity).
• Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients With myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4:652–659. [PMC free article: PMC5885169] [PubMed: 29522138]

  (Among 311 patients with myelofibrosis and thrombocytopenia treated with pacritinib [200 or 400 mg daily] or best available therapy, response rates after 24 weeks were higher with pacritinib [18% vs 3%] while adverse events were more frequent including diarrhea [48% and 67% vs 15%]; no mention of ALT elevations or clinically apparent liver injury).
• Mascarenhas J, Virtgaym E, Stal M, Blacklock H, Gerds AT, Mesa R, Ganly P, et al. Outcomes of patients with myelofibrosis treated with compassionate use pacritinib: a sponsor-independent international study. Ann Hematol. 2018;97:1369–1374. [PMC free article: PMC6019145] [PubMed: 29616317]

  (Among 33 patients with myelofibrosis who had benefitted from pacritinib therapy in a controlled trial that was halted because of a clinical hold who were then restarted and treated for up to 9 more months, there was modest improvements in splenomegaly and 19 patients remained on therapy long term; no mention of ALT elevations or hepatotoxicity).
• Gerds AT, Savona MR, Scott BL, Talpaz M, Egyed M, Harrison CN, Yacoub A, et al. Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Blood Adv. 2020;4:5825–5835. [PMC free article: PMC7686901] [PubMed: 33232476]

  (Among 161 patients with refractory myelofibrosis treated with pacritinib [100, 200 or 400 mg daily], response rates at 24 weeks were low [0% vs 1.8% vs 9.3%] and adverse events were more frequent with the higher doses including diarrhea [19% vs 21% vs 30%], nausea [23% vs 20% vs 28%], abdominal pain [17% vs 11% vs 24%], and fatigue [17% vs 24% vs 24%]; no mention of ALT elevations or hepatotoxicity).
• Tremblay D, Mesa R, Scott B, Buckley S, Roman-Torres K, Verstovsek S, Mascarenhas J. Pacritinib demonstrates spleen volume reduction in patients with myelofibrosis independent of JAK2V617F allele burden. Blood Adv. 2020;4:5929–5935. [PMC free article: PMC7724916] [PubMed: 33275766]

  (Review of the safety and efficacy of pacritinib as therapy of myelofibrosis; no mention of ALT elevations or hepatotoxicity).
• Raghuvanshi R, Bharate SB. Recent developments in the use of kinase inhibitors for management of viral infections. J Med Chem. 2022;65:893–921. [PubMed: 33539089]

  (Review of the kinase inhibitors approved for use in the US, their mechanisms of action and possible role in inhibiting viral replication).
• Verstovsek S, Mesa R, Talpaz M, Kiladjian JJ, Harrison CN, Oh ST, Vannucchi AM, et al. Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia. Haematologica. 2022;107:1599–1607. [PMC free article: PMC9244834] [PubMed: 34551507]

  (Among 189 patients with refractory myelofibrosis and severe thrombocytopenia who were treated with pacritinib or best available therapy, clinical responses were more frequent with pacritinib [23% vs 2%] as were adverse events including diarrhea [61% vs 16%], fatigue [14% vs 11%] and nausea [30% vs 12%]; no mention of ALT elevations or hepatotoxicity).
• Cafardi J, Miller C, Terebelo H, Tewell C, Benzaquen S, Park D, Egan P, et al. Efficacy and safety of pacritinib vs placebo for patients With severe COVID-19: a phase 2 randomized clinical trial. JAMA Netw Open. 2022;5:e2242918. [PMC free article: PMC9855296] [PubMed: 36469321]

  (Among 200 patients hospitalized with severe COVID-19 infection treated with pacritinib or placebo for 14 days, need for mechanical ventilation or extracorporeal oxygenation or death were similar in the two groups [17.2% vs 22.8%] as were adverse event rates [78% vs 80%] and ALT elevations [15% vs 17%].