On September 02, 2015 Geron Corporation (Nasdaq:GERN) reported the publication of two papers in The New England Journal of Medicine (NEJM) in which the company’s telomerase inhibitor, imetelstat, was shown to have disease-modifying activity thought to be associated with selective inhibition of the malignant progenitor cell clones responsible for the underlying disease in two hematologic myeloid malignancies, essential thrombocythemia (ET) and myelofibrosis (MF) (Press release, Geron, SEP 2, 2015, View Source [SID:1234507389]). The papers are available online in the September 3rd issue at www.NEJM.org. Schedule your 30 min Free 1stOncology Demo! "The data in the ET and MF study publications in The New England Journal of Medicine provide compelling evidence that use of a telomerase inhibitor, such as imetelstat, may result in ground-breaking changes in how we approach the future treatment of hematologic myeloid malignancies," said John A. Scarlett, Geron’s President and Chief Executive Officer.
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In the Phase 2 clinical study evaluating imetelstat in ET, all patients achieved a hematologic response, with the majority achieving a hematologic complete response. Rapid and substantial molecular responses observed in the study suggested therapeutic activity of imetelstat on the growth of malignant progenitor cell clones that drive ET. The safety and efficacy results reported in the NEJM publication are consistent with the preliminary data from this study previously presented in part at the annual meetings of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2012 and December 2014, and the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting in June 2013.
"This study was a first look at what happens when you treat ET patients with a drug that has a totally novel mechanism of action," said Dr. David Snyder, City of Hope, Duarte, CA, and co-principal investigator of the ET study. "In the study, imetelstat had a clinically significant effect on disease burden in ET patients."
"The molecular responses suggest that imetelstat may have broad activity across hematologic myeloid malignancies which warrants further clinical study in other myeloproliferative neoplasms," noted Prof. Dr. med. Gabriela M. Baerlocher, Inselspital, Bern University Hospital and University of Bern, Switzerland, and co-principal investigator of the ET study.
In the Phase 2 pilot study evaluating imetelstat in MF patients, unprecedented complete and partial remissions, including reversal of bone marrow fibrosis and molecular responses, were observed. These results suggest the potential value of telomerase-targeting strategies for the treatment of MF, and identify imetelstat as an active drug in this disease. The safety and efficacy results reported in the NEJM publication are consistent with the preliminary data from this study previously presented in part at the annual meetings of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2013 and December 2014.
"The clinical and molecular remissions seen in the study suggest selective anti-clonal activity, not previously documented in current drug treatment of MF," commented Dr. Ayalew Tefferi, Mayo Clinic, Rochester, MN, and principal investigator of the MF pilot study. "A much larger multi-center clinical study is needed to confirm these findings and to further investigate the mechanism by which imetelstat induces clinical responses in some patients."
Future Clinical Development of Imetelstat in Collaboration with Janssen
In November 2014, Geron entered into an exclusive license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize imetelstat worldwide for indications in oncology, including hematologic myeloid malignancies, and all other human therapeutics uses. Under the collaboration with Janssen, development of imetelstat initially will proceed under a mutually agreed clinical development plan which includes a Phase 2 study in MF and a Phase 2 study in myelodysplastic syndrome (MDS). In addition, the clinical development plan may also include additional, possible registration studies in MF and MDS, and possible exploratory Phase 2 and potential follow on Phase 3 studies in acute myeloid leukemia (AML). Certain regulatory, development, manufacturing and promotional activities are being managed through a joint governance structure, with Janssen responsible for these activities.
In July 2015, Janssen initiated IMbark, a Phase 2 clinical study to evaluate the activity of two dose levels of imetelstat in patients with DIPSS intermediate-2 or high-risk MF who have relapsed after or are refractory to a JAK inhibitor. Up to approximately 80 medical centers across North America, Europe and Asia are planned to participate in this clinical study and currently sites are open to patient enrollment. The study is designed to enroll approximately 200 patients (approximately 100 patients per dosing arm). For more information about the IMbark study, please visit View Source
A Phase 2 clinical study in MDS, to be conducted by Janssen, is expected to open for patient enrollment by the end of 2015.
About Imetelstat
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 data suggest that imetelstat shows disease-modifying activity by affecting the malignant clones associated with hematologic myeloid malignancies. 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.