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Phase 1 results demonstrate GALE-401 reduces platelet counts with tolerable safety profile
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Preliminary Phase 2 clinical trial data show promising platelet response with top-line data to be presented mid-year 2015
PORTLAND, Ore., Dec. 8, 2014 (GLOBE NEWSWIRE) -- Galena Biopharma, Inc. (Nasdaq:GALE), a biopharmaceutical company developing and commercializing innovative, targeted oncology treatments that address major medical needs across the full spectrum of cancer care, today announced that data from the Company's Phase 1 clinical trials of GALE-401, or Anagrelide Controlled Release (CR), were presented at the 56th American Society of Hematology (ASH) Annual Meeting & Exposition. The poster presentation also included preliminary data from the ongoing GALE-401 Phase 2 clinical trial in patients with elevated platelet counts due to myeloproliferative neoplasms (MPNs).
"Final data from our GALE-401 Phase 1 trials showed the compound was well tolerated and demonstrated both a reduction in platelet counts and the desired pharmacokinetic profile with our controlled release version of anagrelide, providing the basis for our ongoing Phase 2 clinical trial," said Mark W. Schwartz, Ph.D., President and Chief Executive Officer. "While early, the preliminary Phase 2 trial data, which was also presented at ASH, looks promising with rapid reductions in platelet counts. Our plan is to present top-line data from the Phase 2 trial at a scientific conference in mid-2015."
GALE-401 Phase 1 Clinical Trials
The poster entitled, "Phase 1 Study Results of a Novel Controlled-Release Formulation of Anagrelide (GALE-401) for the Treatment of Thrombocytosis," showed that GALE-401 (Anagrelide CR) is a promising, novel formulation of anagrelide. The Phase 1 trials demonstrated that GALE-401 possesses a pharmacokinetic (PK) profile of a significantly reduced Cmax, or time to maximum plasma concentration, while maintaining adequate plasma exposure needed to induce platelet count reductions in the healthy subjects. Dose-related reductions in platelet counts were observed, and were similar to the marketed immediate release (IR) formulation of anagrelide in a cross-over, multiple dose study. The product was well tolerated with an adverse event (AE) profile that was not distinguishable from placebo.
The Phase 1 trials included 5 studies that enrolled a total of 98 healthy adult subjects, including 12 placebo-control subjects and 86 subjects who received single or multiple doses of Anagrelide CR ranging from 0.2 to 0.6 mg twice daily (b.i.d.) for up to 41 days. The trials included an open-label, single dose developmental study to select a formulation; two placebo-controlled multiple dose ranging studies; a food effect study; and a comparative crossover PK study vs. IR reference product. Safety assessments included laboratory, electrocardiograms (ECGs), and clinical evaluations. Single doses of Anagrelide CR were well tolerated, and the only drug- related AE reported in two or more subjects was headache. In the b.i.d. dose-ranging studies, the frequency and severity of AEs were similar between Anagrelide CR and placebo groups, with the exception of decreased platelet counts in subjects receiving Anagrelide CR. All AEs were transient, mild or moderate in severity, and no severe or serious AEs were reported.
GALE-401 demonstrated dose proportional PK characteristics, and plasma exposure was higher when CR was administered in the fed versus fasted state. In a placebo-controlled study of 0.2 to 0.6 mg b.i.d. dosing for up to 21 days (n=8 subjects/cohort randomized 2:1 to anagrelide or placebo), a dose-related decrease in platelet counts was observed, and the 0.6 mg cohort was halted early due to excessive platelet reductions. In a cross-over, multiple dose study of Anagrelide CR and IR (0.5mg b.i.d., N=20 subjects), similar reductions in platelet counts were observed despite differences in PK exposure.
GALE-401 Phase 2 Preliminary Results
The GALE-401 Phase 2 clinical proof-of-concept study is an open-label, single-arm, multicenter study in patients with an MPN-related thrombocytosis. The primary objective is to estimate the response rate in terms of platelet reduction, and the trial will also assess safety and tolerability, and measure plasma concentrations of anagrelide. The platelet lowering ability of GALE-401 will be measured by the proportion of patients that achieve a complete platelet response (CR = ≤400 x 109/L) or partial platelet response (PR = ≤600 x 109/L or a ≥50% reduction from baseline) maintained for at least four weeks during 24 weeks of treatment. With enrollment complete, patients are being followed for platelet response while they continue study treatment. Safety is assessed by frequency and severity of AEs.
The poster also presented preliminary results for the Phase 2 trial, which enrolled 18 subjects with the following MPNs: 13 Essential Thrombocythemia, 4 Polycythemia Vera, 1 Primary Myelofibrosis. Patients were previously treated with hydroxyurea (n=8), Anagrelide IR (n=6), None (n=7), and were washed out of any prior therapies and their baseline platelet counts were returned to ≥600 x 109/L before treatment with Anagrelide CR.
Patients were started on a dose of 0.5 mg b.i.d. (1.0 mg/day), and titrated at a dose of 0.5 mg/day/wk) to maintain platelet count of 150 - 400 x 109/L. Rapid reductions in platelet counts were observed with dose titration.
Platelet responses to-date include confirmed and unconfirmed CRs and PRs among 9 subjects. AEs have all been Grade 1 or 2 and those reported in two or more subjects regardless of relationship to study drug included headache (5 subjects), abdominal pain (3), fatigue (3), nausea (3), AST elevation (2), diarrhea (2), edema (2), and tachycardia (2).
About GALE-401 (Anagrelide CR)
GALE-401 (Anagrelide CR) contains the active ingredient anagrelide and is a reformulated, controlled release version. The currently available immediate release (IR) formulation is approved by the FDA for the treatment of high platelet counts in patients with myeloproliferative neoplasms (MPNs), including Polycythemia Vera (PV), Chronic Myelogenous Leukemia (CML), Primary Myelofibrosis (PMF), and Essential Thrombocythemia (ET). Adverse events associated with Anagrelide IR, such as nausea, diarrhea, abdominal pain, palpitations, tachycardia, and headache, may be dose and plasma concentration dependent. In Phase 1 studies in healthy adult subjects, GALE-401 was shown to significantly reduce the maximum plasma concentration (Cmax) while maintaining plasma exposure to reduce platelet counts. Thus, GALE-401 may reduce treatment-related adverse events while maintaining effective therapeutic levels to decrease platelet production. GALE-401 is currently being studied in a Phase 2 proof-of-concept clinical trial.
About Myeloproliferative Neoplasms
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), Essential Thrombocythemia (ET), and 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.
About Galena Biopharma
Galena Biopharma, Inc. (Nasdaq:GALE) is a biopharmaceutical company developing and commercializing innovative, targeted oncology therapeutics that address major medical needs across the full spectrum of cancer care. Galena's development portfolio ranges from mid- to late-stage clinical assets, including a robust immunotherapy program led by NeuVax™ (nelipepimut-S) currently in an international, Phase 3 clinical trial. The Company's commercial drugs include Abstral® (fentanyl) Sublingual Tablets and Zuplenz® (ondansetron) Oral Soluble Film. Collectively, Galena's clinical and commercial strategy focuses on identifying and advancing therapeutic opportunities to improve cancer care, from direct treatment of the disease to the reduction of its debilitating side-effects. For more information, visit www.galenabiopharma.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about the progress of the commercialization of Abstral® and development of Galena's product candidates, including GALE-401, patient enrollment in our clinical trials, as well as statements about our expectations, plans and prospects. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those identified under "Risk Factors" in Galena's Annual Report on Form 10-K for the year ended December 31, 2013 and most recent Quarterly Reports on Form 10-Q filed with the SEC. Actual results may differ materially from those contemplated by these forward-looking statements. Galena does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this press release.
CONTACT: Remy Bernarda
VP, Marketing & Communications
(503) 405-8258
rbernarda@galenabiopharma.com
