GALE-401 (Anagrelide CR)
Status: Phase 2/3 Planned
Disease: Essential Thrombocythemia
Our lead program, GALE-401, is a controlled release formulation of anagrelide with product attributes that differentiate it from the currently marketed immediate release formulation. Anagrelide is a drug that has been shown to slow down how fast platelets are made in the bone marrow, and has been approved in the U.S. and Europe for treating high platelets counts in patients with bone marrow disorders.
Anagrelide is currently approved and indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events. Patients with these disorders have extremely high platelet counts, which can cause strokes and heart attacks. Whereas the normal platelet count is 150,000 to 400,000 per microliter, these patients may have platelet counts greater than 1 million. Common side effects of anagrelide, such as palpitations, tachycardia, and headaches, are believed to be associated with maximum or peak plasma concentrations following administration (Cmax). These side effects often limit dose escalation and may result in inadequate control of disease or discontinuation of therapy in over 20% of patients.
To address this medical need, GALE-401’s controlled release version of anagrelide is made to dissolve more slowly than currently marketed versions of this drug. Researchers believe that this slower release of the drug into the blood could help to lower side effects that might be caused by high blood levels when the drug dissolves as quickly as it does with the currently marketed product. GALE-401 reduces the Cmax and maintains the overall plasma exposure of anagrelide, or area under the curve (AUC), over time. Therefore, GALE-401 is expected to decrease the frequency or severity of side effects relative to the immediate release formulation, improving a patient’s ability to tolerate treatment and be titrated to a healthy platelet count.
Multiple Phase 1 studies in which 86 healthy subjects received GALE-401 have shown that the drug exhibits the desired pharmacokinetic (PK) profile. In our Phase 2 trial, GALE-401 demonstrated a potentially faster onset of action, consistent efficacy, and an indication of improved tolerability compared to the immediate release version of anagrelide.
About the Disease
Myeloproliferative neoplasms (MPNs) are a closely related group of hematological malignancies in which the bone marrow cells that produce the body’s blood cells develop and function abnormally. The main MPNs are polycythemia vera (PV), chronic myelogenous leukemia (CML), primary myelofibrosis (PMF), and essential thrombocythemia (ET), all of which are associated with high platelet counts. The MPNs are progressive blood cancers that can strike anyone at any age, and for which there is no known cure.
Thrombocythemia is a myeloproliferative blood disorder. It is characterized by the production of too many platelets in the bone marrow. Too many platelets make normal clotting of blood difficult. It can be either reactive or primary (also termed essential and caused by a myeloproliferative disease). Although often symptomless (particularly when it is a secondary reaction), it can predispose to thrombosis in some patients. Primary Thrombocytosis (essential thrombocythemia or ET) is due to a failure to regulate the production of platelets (autonomous production) and is a feature of a number of myeloproliferative disorders. About a third of patients are asymptomatic at the time of diagnosis. Additional information on ET can be found on the MPN Research Foundation website.