GALE-401 (Anagrelide CR)

Status: Phase 2/3 Planned
Disease: Essential Thrombocythemia

GALE-401 contains the active ingredient anagrelide, an FDA-approved product, for the treatment of patients with myeloproliferative neoplasms ("MPNs") to lower abnormally elevated platelet levels. The currently available immediate release ("IR") version of anagrelide causes adverse events that are believed to be dose and plasma concentration dependent, and may limit the use of the IR version of the drug. Therefore, reducing the maximum concentration ("Cmax") and increasing the half-life of the drug is hypothesized to reduce the side effects, while preserving the efficacy, potentially allowing a broader use of the drug.

Multiple Phase 1 studies in 98 healthy subjects have shown GALE-401 reduces the Cmax of anagrelide and increases the half-life following oral administration, appears to be well tolerated at the doses administered, and to be capable of reducing platelet levels effectively. The Phase 1 program provided the desired PK/PD (pharmacokinetic/pharmacodynamic) profile to enable the initiation of the Phase 2 proof-of-concept trial. The Phase 2, open label, single arm, proof-of concept trial enrolled 18 patients in the United States for the treatment of thrombocytosis, or elevated platelet counts, in patients with MPNs. Final safety and efficacy data from this Phase 2 trial were presented in December 2015 and demonstrated a prolonged clinical benefit with a potentially improved safety profile.

We have analyzed our data and the treatment landscape for MPNs, with a current focus on Essential Thrombocythemia ("ET"). We plan to advance GALE-401 into a Phase 3 clinical trial in patients who are intolerant or resistant to hydroxyurea. The trial will compare GALE-401 (drug arm) versus best available therapy (BAT) to include a sizable population of patients treated with anagrelide IR. After a productive meeting with the U.S. Food and Drug Administration (FDA) in December 2016, we have confirmed that the GALE-401 development program is appropriate for a New Drug Application (NDA) filing using the 505(b)(2) regulatory pathway.

For more information, please contact clinicaltrials@galenabiopharma.com

About the Disease

Essential Thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by the overproduction of platelets by megakaryocytes in the bone marrow. The U.S. prevalence of ET is between 135,000 and 175,000 with approximately seventy-five percent of patients receiving treatment.1 Common symptoms include headache, vision disturbances or migraines, dizziness or lightheadedness, coldness or blueness of fingers or toes, burning, redness, and pain in the hands and feet. Complications for patients with ET include blood clotting or bleeding or may be thrombotic in nature such as stroke, heart attack, or transient ischemic attack.

As with other MPNs, ET is a progressive blood cancer that can strike anyone at any age, and for which there is no known cure; and, there is no single treatment option that is appropriate or effective for all ET sufferers. While some ET patients may be asymptomatic and require no treatment, others may require various treatments and therapies based on the symptoms, their risk factors, and potential complications. The treatment options are limited and are generally hydroxyurea prescribed first line, followed by other treatments including anagrelide immediate release, interferon, aspirin or other agents depending on the patient’s condition. Of these, only anagrelide IR is approved for treatment of ET patients.

1. Mehta et al, (2014) Epidemiology of myeloproliferative neoplasms in the United States, Leukemia & Lymphoma, 55:3, 595-600, DOI: 10.3109/10428194.2013.813500