Geron Announces Initiation of Janssen Phase 2 Clinical Trial of Imetelstat in Myelofibrosis
MENLO PARK, Calif., Sept. 16, 2015 (GLOBE NEWSWIRE) -- Geron Corporation (Nasdaq: GERN) today announced the dosing of the first patient in a Phase 2 clinical trial to evaluate imetelstat in patients with myelofibrosis (MF). This clinical trial, also referred to as the IMbarkTM study, is being conducted by Janssen Biotech, Inc. (Janssen), under the terms of the exclusive worldwide imetelstat license and collaboration agreement between the companies.
Phase 2 Clinical Trial Design
The purpose of the Phase 2 clinical trial is to assess the efficacy, safety and tolerability of two dose levels of single-agent imetelstat in patients with MF. The trial is designed to enroll approximately 200 patients (approximately 100 patients per dosing arm) with DIPSS intermediate-2 or high risk MF who have relapsed after or are refractory to Janus Kinase (JAK) inhibitor treatment. At the time of enrollment, patients must have measurable splenomegaly and symptoms of MF. Patients will be assigned randomly on a blinded basis on a 1:1 ratio to one of two dosing arms – 9.4 mg/kg every three weeks or 4.7 mg/kg every three weeks. Dose reductions for adverse events are allowed and will follow protocol-specified algorithms. An interim review of data from the trial is planned after approximately 20 patients per arm have been randomized and followed for at least 12 weeks, in order to assess the adequacy of one or both of the initial dosing arms. As a result of this interim review, one or both dosing arms could continue as planned, be stopped or modified, or alternative doses could be selected.
The co-primary efficacy endpoints for the trial are spleen response rate and symptom response rate. Spleen response rate is defined as the percentage of patients who achieve ≥ 35% reduction in spleen volume from baseline at the Week 24 visit, as measured by imaging scans and assessed at a central imaging facility and by an Independent Review Committee. Symptom response rate is defined as the percentage of patients who have ≥ 50% reduction in Total Symptom Scores from baseline at the Week 24 visit, based on patient-reported outcomes on a modified Myelofibrosis Symptom Assessment Form version 2.0 electronic diary. The primary efficacy analysis of the co-primary endpoints will occur after all treated patients have been followed for at least 24 weeks.
Secondary efficacy endpoints include the number of patients achieving complete remission (CR) or partial remission (PR), clinical improvement (CI), and anemia, spleen and symptom responses as assessed using the modified 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. These secondary endpoints will be assessed at the time of the primary efficacy analysis. Exploratory endpoints include cytogenetic and molecular responses, as well as leukemia-free survival.
Safety outcomes will be monitored throughout the trial and will include enhanced data collection and reporting for adverse events of interest, including hepatobiliary-associated laboratory findings and hepatic adverse events.
Multiple medical centers across North America, Europe and Asia are planned to participate in the trial. For more information about the IMbarkTM study being conducted by Janssen, please visit http://clinicaltrials.gov/ct2/show/NCT02426086.
Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound, discovered by Geron, is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Preliminary clinical data suggest imetelstat has disease-modifying activity by inhibiting the progenitor cells of the malignant clone associated with hematologic malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies conducted to date include fatigue, gastrointestinal symptoms and cytopenias. Patients in these studies also experienced elevated liver enzymes, which resolved to normal or baseline in the majority of patients followed after imetelstat treatment was withdrawn. Imetelstat has not been approved for marketing by any regulatory authority.
About the Collaboration with Janssen
On November 13, 2014, Geron entered into an exclusive worldwide license and collaboration agreement with Janssen to develop and commercialize imetelstat for oncology, including hematologic myeloid malignancies, and all other human therapeutics uses. Under the terms of the agreement, Geron received an upfront payment of $35 million and is eligible to receive additional payments up to a potential total of $900 million for the achievement of development, regulatory and commercial milestones, as well as royalties on worldwide net sales. Certain regulatory, development, manufacturing and promotional activities are being managed through a joint governance structure, with Janssen responsible for these activities.
Geron is a clinical stage biopharmaceutical company focused on the collaborative development of a first-in-class telomerase inhibitor, imetelstat, in hematologic myeloid malignancies. For more information about Geron, visit www.geron.com.
Use of Forward-Looking Statements
Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that statements in this press release regarding: (i) timing and management of planned and potential clinical trials of imetelstat to be conducted under the collaboration agreement with Janssen, including the current Phase 2 clinical trial in MF, and other potential activities under the collaboration agreement with Janssen; (ii) the safety and efficacy of imetelstat; (iii) the current design of the Phase 2 clinical trial in MF, including planned reviews or analyses of clinical data; (iv) the potential receipt by Geron of additional payments up to a potential total of $900 million for the achievement of development, regulatory and commercial milestones, and royalties from sales of imetelstat; and (v) other statements that are not historical facts, constitute forward-looking statements. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (i) the uncertain, time-consuming and expensive product development and regulatory process, including whether Geron and Janssen will succeed in overcoming all of the clinical safety and efficacy, technical, scientific, manufacturing and regulatory challenges in the development and commercialization of imetelstat; (ii) receiving approvals or clearances from regulatory authorities to proceed with clinical trials; (iii) Janssen's ability to enroll patients in any of the planned or potential clinical trials of imetelstat; (iv) the fact that Janssen may terminate the collaboration agreement for any reason; (v) whether imetelstat is safe and efficacious, and whether any future efficacy or safety results may cause the benefit-risk profile of imetelstat to become unacceptable; (vi) the fact that Geron may not receive any milestone, royalty or other payments from Janssen; (vii) the ability of Geron and Janssen to protect and maintain intellectual property rights for imetelstat; (viii) Geron's dependence on Janssen, including the risks that if Janssen were to breach or terminate the collaboration agreement or otherwise fail to successfully develop and commercialize imetelstat and in a timely manner, Geron would not obtain the anticipated financial and other benefits of the collaboration agreement and the clinical development or commercialization of imetelstat could be delayed or terminated; and (ix) whether imetelstat can be applied to any or to multiple hematologic malignancies. Additional information on the above risks and uncertainties and other factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron's periodic reports filed with the Securities and Exchange Commission under the heading "Risk Factors," including Geron's quarterly report on Form 10-Q for the quarter ended June 30, 2015. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances.