Date: 2016-06-13
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the European Hematology Association 21st Congress
Company: Galena Biopharma (USA - OR)
Product: GALE-401 (anagrelide controlled release )
Action
mechanism: phospholipase A2 inhibitor/platelet aggregation inhibitor. Anagrelide slows down how fast platelets are made in the bone marrow, and has been approved by the FDA for treating high platelets counts in patients with bone marrow disorders. GALE-401 is a new preparation of anagrelide that is made to dissolve more slowly than currently marketed versions of this drug. Because of this, the anagrelide is taken up into the blood more slowly. This slower release of the drug 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.
Disease:
Therapeutic area: Cancer - Oncology - Hematological diseases
Country: USA
Trial
details: The GALE-401 Phase 2 pilot study is a single arm, open label, multi-center study evaluating the efficacy and safety of anagrelide controlled release in subjects with thrombocytosis secondary to essential thrombocythemia (ET) and other myeloproliferative neoplasms (MPNs). The main purposes of this study are to see how well Anagrelide controlled release can control platelet counts in patients with high platelet levels, to see what kind of side effects it causes, and to measure blood levels of the drug. (NCT02125318)
Latest
news: * On June 13, 2016, Galena Biopharma announced that combined safety data from the Company’s GALE-401 clinical trials were presented at the European Hematology Association 21st Congress. A total of six trials have been run with GALE-401, five Phase 1 trials in healthy volunteers (N=98), and one Phase 2 single arm, open label pilot study in MPN patients (N=18). The poster, entitled, “Anagrelide Controlled Release (GALE-401) Safety Profile Consistently Well Tolerated in Myeloproliferative Neoplasms Patients and Healthy Volunteers” was designed to characterize the safety profile of GALE-401 in all subjects treated to date. The results demonstrated that GALE-401 is well tolerated in MPN patients as well as in healthy volunteers. In the Phase 2 study, fewer moderate to severe (Grade 3/4) adverse events (AEs) and fewer AEs per patient (2.3 vs. 3.3) were observed with GALE-401 compared to what has been reported previously with the immediate release (IR) formulation.1 Additionally, for a small subset of subjects treated in the Phase 2 study who were intolerant to anagrelide IR (n=5), GALE-401 appears to offer a longer duration on therapy compared to previous administration of anagrelide IR. Therefore, a randomized trial comparing GALE-401 vs. anagrelide IR in anagrelide naïve subjects, alternatively or together with a trial evaluating anagrelide IR intolerant subjects is warranted. * On December 8, 2015, Galena Biopharma announced the final data from the Company's GALE-401 (anagrelide controlled release (CR)) Phase 2 proof-of-concept clinical trial was presented at the 57th American Society of Hematology (ASH) Annual Meeting. Poster #4074, "Final results of anagrelide controlled-release (GALE-401) safety, efficacy and pharmacokinetics in subjects with myeloproliferative neoplasms (MPN)-related thrombocytosis," presented data on the GALE-401-201, Phase 2, pilot, single arm, open label, multi-center study with eighteen patients enrolled. The study evaluated the safety and efficacy of anagrelide CR in subjects with thrombocytosis secondary to essential thrombocythemia (ET) and other MPNs. The study demonstrated GALE-401 is well tolerated and the efficacy compares favorably to historical anagrelide immediate release (IR) with reported platelet count best response rates, based on the WHO 2008 criteria, of eleven (61.1%) complete responses (CR), four (22.2%) partial responses (PR), and an overall response rate (ORR) of 83.3%. Platelet response is defined as CR (? 400 x 109/L), or PR (? 600 x 109/L or ? 50% reduction from baseline) maintained for at least 4 weeks. The mean time to response, defined as platelet count ? 600 x109/L, ranged from 1 to 9 weeks with GALE-401, which compares favorable to historical anagrelide IR, where time to response ranged from 4 to 12 weeks. Fourteen of 18 subjects enrolled experienced a treatment related adverse event (AE); however, the vast majority of AEs were Grade 1/2 with no patients discontinuing therapy due to progression of disease. Nine patients remain on trial and the median time of response has not yet been reached. The primary objective for the trial was to estimate the overall platelet response rate (ORR) with secondary objectives of safety, tolerability and pharmacokinetics (PK). Eligible patients met the following criteria: male or female ? 18 years of age; diagnosed with a MPN related elevated platelet count to include ET, chronic myelogenous leukemia, polycythemia vera, or primary myelofibrosis; platelet count ? 600 109/L on two occasions at least 14 days apart prior to first dose of study drug; for patients with MPN diagnosis other than ET, concurrent anti-MPN treatment was permitted, provided that the doses were stable at least four weeks prior to first dose of study drug; and, patients were not receiving therapy specifically intended to reduce platelet counts. GALE-401 was administered at a starting dose of 0.5 mg twice daily (1.0 mg/day) and the dose was titrated at weekly intervals, on an individual basis, to determine the lowest dose required to achieve and maintain a target platelet count of 150-400 x 109/L. Toxicities were based on NCI CTCAE v4.03. * On June 15, 2015, Galena Biopharma announced that data from the Company's Phase 2 clinical trial of GALE-401 was presented at the European Hematology Association 20th Congress in Vienna, Austria. The GALE-401 Phase 2 pilot study is a single arm, open label, multi-center study evaluating the efficacy and safety of anagrelide controlled release in subjects with thrombocytosis secondary to essential thrombocythemia (ET) and other myeloproliferative neoplasms (MPNs).The Phase 2 study demonstrated that GALE-401 was well tolerated with primarily Grade 1 and 2 toxicities in 16 of the 18 subjects enrolled. The efficacy shown in the trial compares favorably to historical anagrelide immediate release (IR) response rates with the following platelet response: overall response rate (ORR) of 78% (14/18); complete response (CR) of 39% (7/18); partial response (PR) of 39% (7/18). The median time to response was 5 weeks (range, 3--10), and the median duration of response has not yet been reached. Based on the data, the investigators concluded that GALE-401 remains a viable potential treatment option for MPNs, and a randomized trial comparing GALE-401 versus anagrelide IR is warranted. Final data from the GALE-401 Phase 2 trial is expected to be presented at the American Society of Hematology conference in December.
In the healthy volunteer studies, single and multiple doses of GALE-401 were safe and well tolerated and there were no clinically relevant changes in vital signs, electrocardiograms, and safety laboratory parameters other than a reduction in platelet counts. The most frequent treatment emergent adverse events reported included headache, pain in extremities or back, palpitations and gastrointestinal disturbances. In the Phase 2 MPN trial, patients treated with GALE-401 exhibited fewer of the more common adverse events associated with anagrelide IR (cardiac; general; gastrointestinal; respiratory, thoracic, and mediastinal; skin and subcutaneous tissue; nervous system). Some of the less common AEs of anagrelide IR were comparatively more frequent for GALE-401 (vascular; hepatobiliary; blood and lymphatic).
The primary objective of the study was to estimate ORR with the secondary objectives of safety, tolerability and pharmacokinetics (PK). Enrolled patients were adult men and women diagnosed with an MPN-related elevated platelet count to include chronic myelogenous leukemia (CML), polycythemia vera (PV), primary myelofibrosis (PMF), or ET. Patient eligibility requirements also included:
• Platelet count >= 600 K/?L on two occasions at least 14 days apart prior to first dose of study drug
• MPN diagnosis other than ET, concurrent anti-MPN treatment was permitted, provided that the doses are stable at least 4 weeks prior to first dose of study drug
• Currently not receiving therapy specifically intended to reduce platelet counts
• Adequate hepatic function
GALE-401 was administered at a starting dose of 0.5 mg twice daily (1.0 mg/day). The dose was titrated at weekly intervals, on an individual basis, to determine the lowest dose required to achieve and maintain a target platelet count of 150--400 K/?L. Platelet response is defined as complete response (CR, <= 400 K/?L) or partial response (PR, <= 600 K/?L or >= 50% reduction from baseline) maintained for at least 4 weeks.
The poster presentation, entitled, "Phase 2 Study of a Novel Controlled-Release Formulation of Anagrelide (GALE-401) in Subjects with Myeloproliferative Neoplasm (MPN)-Related Thrombocytosis," was presented on Saturday, June 13, 2015.
