CTI BioPharma Corp. announced the US Food and Drug Administration (FDA) has approved 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. Vonjo is a novel oral kinase inhibitor with specificity for JAK2 and IRAK1, without inhibiting JAK1. The recommended dosage of Vonjo is 200 mg orally twice daily. Vonjo is the first approved therapy that specifically addresses the needs of patients with cytopenic myelofibrosis.

"Today's approval of Vonjo establishes a new standard of care for myelofibrosis patients suffering from cytopenic myelofibrosis," said John Mascarenhas, M.D., Associate Professor, Medicine, Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "Myelofibrosis with severe thrombocytopenia, defined as blood platelet counts below 50 × 109/L, has been shown to result in poor survival outcomes coupled with debilitating symptoms. Limited treatment options have rendered this disease as an area of urgent unmet medical need. I am pleased to see that a new, efficacious and safe treatment option is now available for these patients."

"In the US, there are approximately 21,000 patients with myelofibrosis, two-thirds of which have cytopenias (thrombocytopenia or anaemia), commonly resulting from the toxicity of other approved therapies. Severe thrombocytopenia, defined as a blood platelet count below 50 × 109/L, occurs in one-third of the overall myelofibrosis population, and has a particularly poor prognosis. With the approval of Vonjo, we are excited to now be able to offer a new therapy that is specifically approved for patients with cytopenic myelofibrosis. We are fully funded for commercial launch, following our debt and royalty transactions with DRI, and we look forward to providing Vonjo, the potential best-in-class therapy for cytopenic myelofibrosis patients, to patients within 10 days," said Adam R. Craig, M.D., Ph.D., president and chief executive officer of CTI Biopharma. "I would like to thank the patients, caregivers, clinical trial staff and investigators who made the Vonjo clinical trials possible. I am also thankful to the CTI team for their hard work and dedication and their focus on the needs of patients."

The accelerated approval is based on efficacy results from the pivotal phase 3 PERSIST-2 study of Vonjo in patients with myelofibrosis (platelet counts less than or equal to 100 × 109/L). Patients were randomized 1:1:1 to receive Vonjo 200 mg twice daily (BID), Vonjo 400 mg once daily (QD) or best available therapy (BAT). Prior JAK2 inhibitor therapy was permitted. In this study, in the cohort of patients with baseline platelet counts below 50 × 109/L who were treated with pacritinib 200 mg BD, 29% of patients had a reduction in spleen volume of at least 35% compared to 3% of patients receiving best available therapy, which included ruxolitinib. As part of the accelerated approval, CTI is required to describe a clinical benefit in a confirmatory trial. To fulfil this post-approval requirement, CTI plans to complete the PACIFICA trial, with expected results in mid-2025.

The most common adverse reactions (=20%) following Vonjo 200 mg twice daily were diarrhoea, thrombocytopenia, nausea, anaemia and peripheral edema. The most frequent serious adverse reactions (=3%) following Vonjo 200 mg twice daily were anaemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia and squamous cell carcinoma of skin.

CTI is committed to supporting patients with myelofibrosis and removing barriers to access. As part of that commitment, CTI has established CTI Access, a patient support programme that provides reimbursement and financial assistance programs for eligible patients.

Under the terms of the previously announced debt and royalty transaction with DRI Healthcare Trust, the FDA approval of Vonjo triggers the acquisition by DRI of a tiered royalty on Vonjo for US$ 60 million. The proceeds of the transactions will be used by CTI to fund the launch of Vonjo. As of December 31, 2021, CTI had cash and cash equivalents of approximately $65 million.

Pacritinib is an oral kinase inhibitor with activity against wild type Janus Associated Kinase 2 (JAK2), mutant JAK2V617F form and FMS-like tyrosine kinase 3 (FLT3), which contribute to signalling of a number of cytokines and growth factors that are important for haematopoiesis and immune function. Myelofibrosis is often associated with dysregulated JAK2 signalling. Pacritinib has higher inhibitory activity for JAK2 over other family members, 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.

Vonjo is indicated 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. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Myelofibrosis is bone marrow cancer that results in formation of fibrous scar tissue and can lead to thrombocytopenia and anaemia, weakness, fatigue and an enlarged spleen and liver. Within the US, there are approximately 21,000 patients with myelofibrosis, 7,000 of which have severe thrombocytopenia (defined as blood platelet counts below 50 × 109/L). Severe thrombocytopenia is associated with poor survival and high symptom burden and can occur as a result of disease progression or from drug toxicity with other JAK2 inhibitors, such as JAKAFI and INREBIC.

CTI BioPharma Corp. is a commercial biopharmaceutical company focused on the acquisition, development and commercialization of novel targeted therapies for blood-related cancers that offer a unique benefit to patients and their healthcare providers.