Information about Imetelstat: the first clinical stage telomerase inhibitor

Clinical research and trials

Imetelstat has been evaluated and tested in a variety of clinical trials and for various indications. Here you can find an overview of past and current clinical trials, as well relevant reports, presentations and abstracts from those trials.


Efficacy and Safety of Imetelstat in RBC Transfusion-Dependent (TD) IPSS Low/Int-1 MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agents (ESA) (IMerge)

P. Fenaux et al (2017)


In IPSS Low/Int-1 RBC transfusion dependent MDS patients relapsed/refractory to ESA, TI was observed in 34% and erythroid HI in 63% with imetelstat therapy. TI response appeared to be independent of sEPO level. Reversible cytopenias were the most frequent adverse events, which were generally manageable with dose reduction or delays. Elevated LFTS were reversible. Patients who were naïve to lenalidomide and HMAs and who lacked del(5q) had a higher rate of durable TI (54%) than other groups, which should be further explored.

ASH2017, abstract 4256

Imetelstat, a telomerase inhibitor, differentially affects normal and malignant megakaryopoiesis

G. Mosoyan et al (2017)

Imetelstat (GRN163L) is a specific telomerase inhibitor which has demonstrated clinical activity in patients with myeloproliferative neoplasms (MPN) and in patients with solid tumors. Our results indicate that the delay observed in normal MK maturation may account for imetelstat-induced thrombocytopenia, while the more global effects of imetelstat on several stages along the hierarchy of MPN megakaryopoiesis may be responsible for the favorable clinical outcomes reported in MPN patients.

(Leukemia online, 08 March 2017)

Imetelstat for treatment of myelofibrosis

J. Mascarenhas et al (, 10 Dec 2016)

Areas covered: The pre-clinical rationale for the use of the telomerase inhibitor, imetelstat, in patients with advanced MF and essential thrombocythemia (ET) will be reviewed as well the results of the initial clinical trials with this agent.

Expert opinion: Results from a single institution pilot study of imetelstat therapy have been reported and indicate a signal of activity. This approach appears to have the potential to reverse bone marrow histomorphologic abnormalities, induce molecular responses, and target the malignant hematopoietic stem cell population in MF patients. Results from a randomized, multi-center, phase II trial in MF are ongoing.


Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management

A. Tefferi (American Journal of Hemtaology, November 2016)

Content: disease overview, diagnosis, risk stratification, risk adapted therapy.

Regarding imetelstat:

'Currently, many other drugs are being tested for their therapeutic value in MF and the most intriguing results were recently reported with the use of imetelestat, which is a 13-mer lipid-conjugated oligonucleotide that targets the RNA template of human telomerase reverse transcriptase. In the particular study, imetelstat was administered as a 2-hour intravenous infusion (9.4 mg per kilogram of body weight) every 1 to 3 weeks. A complete or partial remission occurred in 7 of 33 patients (21%), with a median duration of response of 18 months for complete responses. Bone marrow fibrosis was reversed in all 4 patients who had a complete response, and a molecular response occurred in three of the four patients.'

Dynamics of Telomere Length Reflect the Clonal Suppression Seen with the Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia

Monika Haubitz et al (ASH2016, abstract 91467)

The lower TLV found in granulocytes of pts with MPN and especially with MF compared to healthy individuals reflect the higher mitotic history of malignant clones. In the ET imetelstat cohort, the very low TLV found at baseline might result from longer disease duration and resistance and/or intolerance to prior therapies. The higher TLV observed after 9 months of treatment with imetelstat and correlation with the reduction in the driver mutational burden suggests that imetelstat treatment in ET pts may suppress neoplastic clones and, in the absence of a high additional mutational burden, favor recovery of normal hematopoiesis.

Telomerase as a Cancer Target. Development of New Molecules

M. Gomez et al (2016)

Telomeres are the terminal part of the chromosome containing a long repetitive and non-codifying sequence that has as function protecting the chromosomes. In normal cells, telomeres lost part of such repetitive sequence in each mitosis, until telomeres reach a critical point, triggering at that time senescence and cell death. However, in most of tumor cells in each cell division a part of the telomere is lost, however the appearance of an enzyme called telomerase synthetize the segment that just has been lost, therefore conferring to tumor cells the immortality hallmark. Telomerase is significantly overexpressed in 80–95% of all malignant tumors, being present at low levels in few normal cells, mostly stem cells. Due to these characteristics, telomerase has become an attractive target for new and more effective anticancer agents.

In this work, we analyze the different strategies for telomerase inhibition, either in development, preclinical or clinical stages taking into account their strong points and their caveats.

Imetelstat - First in Class, First in Clinic Telomerase Inhibitor: Current Status

S. Gryaznov, 12th Annual Meeting of the Oligonucleotide Therapeutics Society on September 28, 2016

Human telomerase is a unique reverse transcriptase, which is present in est. 85% of all primary tumor samples, while its activity is not detected in majority of normal tissues. This enzyme is responsible, among some other emerging functions, for maintaining telomere length and overall telomere and thus chromosomal stability of cancer cells. Hence, it is hypothesized, that inhibition of telomerase may provide an almost universal approach to specific cancer treatment.

Imetelstat , (a.k.a. GRN163L) , is a recently developed uniformly sugar - phosphate back bone modified oligonucleotide N3’ - P5’ thio - phosphoramidate 13 - mer, containing 5’ - conjugated lipid ( palmitic ) group. The molecule is not an antisense compound, but a direct telomerase enzyme inhibitor . It is a telomerase template antagonist that is fully complementary to the functionally important template region of telomerase RNA component (hTR). Imetelstat is a highly potent and sequence - specific inhibitor of telomerase, as demonstrated with various in vitro and in vivo animal models. This compound has advanced to several Phase 1 / 2 clinical trials to treat hemat o logic malignances and solid tumors. Currently, the main clinical focuses are myelofibros i s (MF), Phase 2 IMbark TM trial and myelodysplastic syndrome (MDS), Phase 2/3 IMerge TM trial .

Key activity - defining bio - chemical properties, as well as initial clinical data for Imetelstat will be presented.

Dr. Gryaznov is a Senior Director of Oligonucleotide Chemistry with Nucleic Acid Center of Excellence at Alios BioPharma, which is a part of the Janssen Pharmaceutical Companies. Prior to this appointment, he worked as a Director of Chemistry and Senior Research Fellow with Geron Corporation, where he defined major scientific and drug-discovery directions for the companies. While at Geron, Dr. Gryaznov developed new and broad-spectrum nucleic acid mimetic-based therapeutic discovery platform - oligo-N3’-P5’-(thio)-phosphoramidates, resulting in the discovery of first-in-class, first-in-clinic telomerase inhibitor Imetelstat (GRN163L), which is currently in multiple Phase II trials to treat hematological cancers.

Dr. Ayalev Tefferi to speak at the 2nd Annual SF Bay Area MPN Conference for Patients on 17 September 2016

This is the 2nd Annual SF Bay Area MPN Conference for Patients. You will have the opportunity to hear the latest research and engage with four experts in the MPN clinical and scientific community. Confirmed to attend are Dr. Ayalew Tefferi from the Mayo Clinic, Dr. Ross Levine from Memorial Sloan Kettering Cancer Center, Dr. Vincent Ho from Dana-Farber Cancer Institute and Dr. Lloyd Damon from UCSF Medical Center. The event will include the latest research, therapies and news from our distinguished guests. This is a full-day event that will allow plenty of time for your questions and an opportunity to connect with other people living with PV, ET and MF. To ensure the proper ratio of patient and family members to medical experts, we are limiting the meeting to the first 100 people who sign up.


  • 9:00  – 9:30  Arrival and social time
  • 9:30 –  9:45  Welcome (Auditorium) Dr. Tefferi
  • 9:45 – 10:45  Dr. Lloyd Damon - Pregnancy and MPN's
  • 10:45 – 11:45  Dr. Ross Levine - Update in Labratory Research in MPN's
  • 11:45 – 12:45  Lunch
  • 12:45 –  1:45  Dr. Ayalew Tefferi - Update in Prognostication and Treatment in MPN's
  • 1:45 –  2:45  Dr. Vincent Ho - Update in Transplant for MF
  • 2:45 –  5:00  Panel session with doctors

Dr. Alessandro Vannucchi speaks about imetelstat at the European focus meeting on MPN in Zagreb

2016 European Focus on Myeloproliferative Neoplasms & Myelodysplastic Syndromes held in Zagreb, Croatia (5-7 May 2016)

This webcast of the 2016 European Focus on Myeloproliferative Neoplasms & Myelodysplastic Syndromes held in Zagreb, Croatia from 5-7 May 2016 addresses the most intriguing and clinically applicable topics and data, outlines key learning points, and reinforces the take-home messages regarding the treatment of MPN and MDS from the Congress.

In this presentation, Dr. Alessandro M. Vannucchi discusses the use of novel agents and combination therapies in the treatment of myelofibrosis (MF).

(imetelstat is discussed at 5:52)

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children’s Oncology Group

M.M. Gramatges et al (30 June 2016)

Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Our results suggest that TC (editor: Telomere Content) at end of AML induction is associated with hematopoietic reconstitution capacity independently of age and may identify those at highest risk for markedly delayed bone marrow recovery after AML therapy.

Click here for the original abstract at Journal of Clinical Oncology.

See also ScienceDaily:

"Telomere length is indicator of blood count recovery in treatment of Acute Myeloid Leukemia"

Click here for the ScienceDaily article.

Telomerase in hematologic malignancies

C. Bruedigam, S.W. Lane (Hematology, July 2016)

Telomerase inhibition has shown remarkable efficacy in myeloid malignancies, and current and future preclinical and clinical studies are necessary to comprehensively investigate its underlying mechanism of action. Future work should identify the potential genetic susceptibilities to telomerase inhibition therapy, and evaluate rational combinations of telomerase inhibitors with chemotherapy and other novel agents. Robust preclinical evaluation is essential to best translate these new agents successfully into our clinical treatment algorithm for myeloid and other blood cancers.

Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies

Mohammad A. Jafri, Shakeel A. Ansari, Mohammed H. Alqahtani, Jerry W. Shay (Genome Medicine, 20 June 2016)

Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Here, we summarize telomere organization and function and its role in oncogenesis. We also highlight genomic mutations that lead to reactivation of telomerase, and mechanisms of telomerase reconstitution and trafficking that shed light on its function in cancer initiation and tumor development. Additionally, recent advances in the clinical development of telomerase inhibitors, as well as potential novel targets, will be summarized.

The telomerase inhibitor imetelstat in patients (pts) with intermediate-2 or high-risk myelofibrosis (MF) previously treated with Janus kinase (JAK) inhibitor: A phase 2, randomized study.

A. Tefferi et al (2016)

MF is a Philadelphia chromosome negative myeloproliferative neoplasm, with a relatively poor prognosis. Ruxolitinib, a JAK1/JAK2 inhibitor, is the only approved therapy for MF, and there are no approved treatment options for pts who fail ruxolitinib. There is a great unmet need for effective therapy for this pt population. Imetelstat sodium is a 13-mer oligonucleotide that specifically targets the RNA template of human telomerase and is a potent competitive inhibitor of telomerase enzymatic activity (Asai et al, Cancer Res 2003; Herbert et al, Oncogene 2005). A pilot study of imetelstat therapy in MF demonstrated complete and partial remissions, including some molecular remissions (Tefferi et al, N Engl J Med2015). Based on the novel mechanism of action imetelstat may provide clinical benefit to pts with intermediate-2 or high-risk MF with refractory/relapsed disease after JAK inhibitor therapy.

(2016 ASCO Annual Meeting, Abstract No:  TPS7079, Monday June 6)

for the Poster clicke here

Impact of hypomethylating agents on hTERT expression and synergistic effect in combination with imetelstat, a telomerase inhibitor, in AML cell lines

J. Rusbuldt et al (2016)

Decitabine (DAC) and azacitidine (AZA) are DNA methyltransferase inhibitors (DNMTIs) used in the treatment of AML. Combining imetelstat and DNMTI may be an improved treatment option for AML. We investigated effects of DAC and AZA on hTERT expression and cell viability in AML cell lines OCI-AML3 and OCI-AML5, and evaluated growth inhibition when combined with imetelstat. Dose-dependent synergistic activity was demonstrated for DAC followed by imetelstat: OCI-AML3 cell viability changed from 95% with DAC to 61% and 10% after 2 and 4 weeks of imetelstat, respectively; OCI-AML5 cell viability changed from 46% with DAC to 6% and 1% after 2 and 4 weeks of imetelstat, respectively.

AACR,19 April 2016, Abstract 2731

(Co-authored by Janssen Research & Development, LLC, Spring House, PA)

Current Developments in Myelofibrosis Treatment

S. Verstovsek (2016)

In this video Dr. Srdan Verstovsek presents about MF and how current therapies fail to cure or to extend life expectancy significantly. From all the new drug developments (such as ACE011, JAK1 inhibitors, LOXL2, Hedgehog inhibitors, PRM151, LCL161, Bcl-xl inhibitors, IL3R, PD1 inhibitors) he elaborates about imetelstat starting on 20.20 of the video, calling it one of the two hottest drugs in development. The other is PRM151.

(a Cancer & Research Treatment Fund -CR&T- meeting, convened by MPN expert Dr. Richard Silver)

Myelosuppression in patients treated with the telomerase inhibitor imetelstat is not mediated through activation of toll-like receptors

G. Baerlocher et al (2016)

Ex vivo studies have provided evidence that imetelstat may induce thrombocytopenia in patients with myeloproliferative neoplasms by blocking the terminal maturation of normal megakaryocyte precursors: megakaryocytic differentiation requires upregulation of telomerase activity which is inhibited by imetelstat. Correct understanding of the MOA of imetelstat is vital to guide its clinical use and strategies to mitigate thrombocytopenia in patients with myeloproliferative neoplasms.

AACR, 19 April 2016, Abstract 2732

(co-authored by Janssen Research & Development, LLC, Spring House, PA)

Emerging Issues of Myeloproliferative Neoplasms Research 2016

A. Tefferi, Indianapolis, 12 March 2016

Ayalev Tefferi presented at the 13th Annual St. Vincent’s Cancer Care Indy Hematology Review 2016. This presentation gives an overview of prevealance of mutation status in MPN's, including diagnosis, prognosis and risk stratification. He also presents about responses of various JAK inhibitors and imetelstat in the treatment of Myelofibrosis.

(link goes directly to Tefferi's powerpoint presentation)

Imetelstat therapy in refractory anemia with ring sideroblasts with or without thrombocytosis

A. Tefferi et al (2016)

Three (38%) of eight transfusion-dependent patients became transfusion-independent at a median time of 11 weeks (range, 9–14) and their response lasted for a median of 28 weeks (range, 9–37; Figure 1); one of the three patients also had resolution of leukocytosis and thrombocytosis. A fourth patient experienced >50% decrease in palpable spleen size (16 cm at baseline) and a decrease in transfusion need. Two additional patients with thrombocytosis and leukocytosis experienced normalization of counts. The current study suggests drug activity in imetelstat-treated patients with RARS or RARS-T. Further investigation on the therapeutic benefit of imetelstat in RARS/RARS-T is warranted.

(Blood Cancer Journal, 11 March 2016)

A molecular biology and phase II study of imetelstat (GRN163L) in children with recurrent or refractory central nervous system malignancies

R. Salloum et al (2016)

Telomerase activation is critical in many cancers including central nervous system (CNS) tumors. Imetelstat is an oligonucleotide that binds to the template region of the RNA component of telomerase, inhibiting its enzymatic activity. We conducted an investigator-sponsored molecular biology (MB) and phase II study to estimate inhibition of tumor telomerase activity and sustained responses by imetelstat in children with recurrent CNS malignancies.

Most common grade 3/4 toxicities included thrombocytopenia (32.5 %), lymphopenia (17.5 %), neutropenia (12.5 %), ALT (7.5 %) and AST (5 %) elevation. Two patients died of intratumoral hemorrhage secondary to thrombocytopenia leading to premature study closure. No objective responses were observed. Telomerase inhibition was observed in peripheral blood mononuclear cells (PBMCs) for at least 8 days.


Activity of the Telomerase Inhibitor GRN163L (Imetelstat) on Acute Myeloblastic Leukemia Blasts Is Enhanced By DNA Methyltransferase Inhibitors Irrespective of TERT Promoter Methylation Status

C.R. Cantilena et al (2015)

Conclusion: High risk primary leukemias are susceptible to killing by the telomerase inhibitor irrespective of the degree of methylation of the hTERTpro/Ex1 region. Furthermore, demethylating agents can enhance the activity of the telomerase inhibitor, imetelstat. These findings suggest that combination therapy of imetelstat and DNMT inhibitors may have synergistic anti-leukemic efficacy in high risk AML patients.

(ASH 2015, abstract 1267)

Imetelstat Pilot Study Data Released for MPN

A. Gerd, ASH2015

Aaron Gerds, MD Taussig Cancer Institute, Department of Hematology & Medical Oncology Cleveland Clinic discusses Imetelstat Pilot Study Data Released for MPN Patient

(OncologyTube, ASH2015)

Dynamics of Mutations in Patients with ET Treated with Imetelstat

E. Oppliger Leibundgut et al (2015)

(ASH 2015, abstract 57)

Telomerase Inhibitor Imetelstat Therapy in Refractory Anemia with Ring Sideroblasts with or without Thrombocytosis

A. Tefferi et al (2015)

Conclusions: Treatment with imetelstat may offer clinical benefit in patients with RARS or RARS-T with generally acceptable safety profile and warrants further clinical investigation.

(ASH 2015, abstract 55)

Telomerase Targeting Drug Demonstrates Benefit in Myelofibrosis Treatment

A. Tefferi (2015)

Imetelstat, a novel drug that targets telomerase, has demonstrated potential value in treating patients with myelofibrosis, according to the results of a study published today in the New England Journal of Medicine. Tefferi: "Get rid of the cancer; that's what imetelstat does."

(Mayo Clinic, YouTube)

Telomerase inhibitor imetelstat

G.M. Baerlocher (2015)

In this video Gabriela Baerlocher, MD, explains about telomerase, imetelstat and the phase 2 clinial trial on MF that has started at 80 locations. Baerlocher: "Such rapid and durable hematologic and molecular responses have not been seen so far with standard treatments".

(CurrentMedicineTV, The Health Care Channel)

A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis

A. Tefferi et al. (2015)

Imetelstat is a 13-mer lipid-conjugated oligonucleotide that targets the RNA template of human telomerase reverse transcriptase. We sought to obtain preliminary information on the therapeutic activity and safety of imetelstat in patients with high-risk or intermediate-2–risk myelofibrosis. A complete or partial remission occurred in 7 patients (21%). Bone marrow fibrosis was reversed in all 4 patients who had a complete response, and a molecular response occurred in 3 of the 4 patients.

(The New England Journal of Medicine)

Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia

G.M. Baerlocher et al (2015)

Imetelstat, a 13-mer oligonucleotide that is covalently modified with lipid extensions, competitively inhibits telomerase enzymatic activity . Rapid and durable hematologic and molecular responses were observed in patients with essential thrombocythemia who received imetelstat.

(The New England Journal of Medicine)

A. Tefferi at St.Vincent: Myeloproliferative Neoplasms 2015


Dr. Ayalew Tefferi, MD Mayo Clinic, Rochester, MN, provides an update on Chronic Myeloid Malignancies; diagnosis, various mutations involved and potential treatments. Slides 43-49 are exclusivey about imetelstat . Clinical findings:

• Overall hematologic response in 100% of patients (n = 18)
• Complete response (CR) in 16 of 18 (88.9%) patients
• Partial response (PR) in 2 of 18 (11.1%) patients
• Clinicohematologic CR in 17 of 18 (94.4%) patients

Imetelstat received Orphan Drug Designation

FDA (11 June, 2015)

The Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.

Study to Evaluate Activity of 2 Dose Levels of Imetelstat in Participants With Intermediate-2 or High-Risk Myelofibrosis (MF) Previously Treated With Janus Kinase (JAK) Inhibitor

A Randomized, Single-Blind, Multicenter Phase 2 Study to Evaluate the Activity of 2 Dose Levels of Imetelstat in Subjects With Intermediate-2 or High-Risk Myelofibrosis (MF) Relapsed/Refractory to Janus Kinase (JAK) Inhibitor

A Pilot Open-Label Study of the Efficacy and Safety of Imetelstat (GRN163L) in Myelofibrosis and Other Myeloid Malignancies

A Pilot Open-Label Study of the Efficacy and Safety of Imetelstat (GRN163L) in Myelofibrosis and Other Myeloid Malignancies.

This pilot clinical trial studies how well imetelstat sodium works in treating patients with primary or secondary myelofibrosis and other myeloid malignancies. Imetelstat sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Beyond JAK2 Inhibitors: New targets and new agents

S. Verstovsek (2015)

In this presentation, Dr. Srdan Verstovsek discusses new targets and agents in the treatment of myelofibrosis. This webcast is part of a series that focuses on current practices, management approaches, and emerging treatment options, such as PRM151 and imetelstat.

(European Focus on Myeloproliferative Neoplasms and Myelodysplastic Syndromes, Zagreb, Croatia, 24-26 April 2015)

Completed: Open Label Study With Imetelstat to Determine Effect of Imetelstat in Patients w/ Previously Treated Multiple Myeloma

This is an open label Phase II study to determine the rate of improvement in response of patients with previously treated multiple myeloma to imetelstat alone or in combination with lenalidomide maintenance therapy. This study will include multiple myeloma patients who either have achieved disease stabilization or who have achieved at least a partial response (PR) but failed to achieve a complete response (CR) after cytoreductive therapy for multiple myeloma; ie, have detectable but non-progressing disease and will most likely relapse.

(see ASH2012 abstract here )


Monitoring of Calr Allele Burden in Patients with Essential Thrombocythemia Treated with Imetelstat, a Telomerase Inhibitor, Reveals Rapid and Substantial Molecular Responses

G.M. Baerlocher et al. (2014)

In 4 of 5 patients with CALR-mutated ET, IT induced a rapid CR and in 3 patients hematologic CR was associated with a substantial decrease in the allele burden of 35-50% after 4 months which is more rapid than what has so far been seen with other treatments for ET. Overall 9/13 patients with JAK2 or CALR mutations reached a >35-50% decrease of the mutant clone within 4 months of treatment with IT, providing clinical confirmation of imetelstat’s inhibition of neoplastic clonogenic cell growth in vivo . This additional evidence of reduction in the clonal burden supports IT’s potential to modify the biology of MPNs long-term.

Geron to Assume Sponsorship of Myelofibrosis IST and IND

Menlo Park, Calif., August 5, 2014

Geron Corporation (Nasdaq: GERN) announced today that the company has entered into a transfer agreement with Mayo Clinic whereby the Investigational New Drug (IND) application for imetelstat under which the investigator-sponsored clinical trial of imetelstat in myelofibrosis (Myelofibrosis IST) has been conducted will be transferred from Mayo Clinic to Geron. In addition, Geron will assume sponsorship for the Myelofibrosis IST, and Dr. Ayalew Tefferi will remain the principal investigator for the study.

Imetelstat, a Telomerase Inhibitor, Therapy for Myelofibrosis: A Pilot Study

A. Tefferi et al. (2014)

A phase-2 study in essential thrombocythemia showed platelet-lowering activity of imetelstat accompanied by reduction in JAK2 V617F allele burden, thus providing the main rationale for conducting the current study.

The current study identifies imetelstat as an active drug in patients with MF, but also reveals its potential to cause significant myelosuppression. The association between CR/PR and specific mutations suggests potential targeted activity that might be exploited for patient and disease selection.


Imetelstat, a Telomerase Inhibitor, Induces Morphologic and Molecular Remissions In Myelofibrosis and Reversal Of Bone Marrow Fibrosis

A. Tefferi et al. (2013)

The current study signifies the potential value of telomerase-based treatment strategies in MF and identifies imetelstat as an active drug in that regard. The observed morphologic and molecular remissions confirm selective anti-clonal activity, which has thus far eluded other drugs in MF, including JAK inhibitors.


Imetelstat: A novel approach with robust hematologic and molecular responses in a phase 2 study in patients with essential thrombocythemia (ET) who are refractory or intolerant to prior therapy

G.M. Baerlocher et al. (2013)

Imetelstat appears to be a promising treatment for ET. Treatment in 18 ET patients who had previously failed or were intolerant to conventional therapies resulted in 100% hematologic responses (88.9% CR). Molecular responses (PR) were reached in 7 / 8 patients (88%) and were maintained in 6 patients.

A median 93% reduction of neoplastic clonogenic growth in patients after 1-2 months of treatment was demonstrated in the 5 patients tested, confirming prior ex vivo data.

(2013 Hematology Annual Meeting, Stockholm)

Video presentation by Baerlocher here

A Phase I Trial of Imetelstat in Children with Refractory or Recurrent Solid Tumors

P. Thompson (2013)

Imetelstat is a covalently-lipidated 13-mer thiophosphoramidate oligonucleotide that acts as a potent specific inhibitor of telomerase.The purpose of this study was to determine the recommended phase II dose of imetelstat in children with recurrent or refractory solid tumors.

2012 and before:

The Telomerase Inhibitor, Imetelstat, Rapidly Reduces Myeloma Cancer Stem Cells (CSCs) in a Phase II Trial

C.A. Huf et al. (2012)

MM cells are relatively resistant to a wide range of anti-myeloma agents. In preclinical models, the novel telomerase inhibitor imetelstat has been found to inhibit CSCs from a wide range of tumor types, and we reported that imetelstat reduced TA in MM CSCs resulting in the loss of self-renewal and clonogenic growth potential. ../..

These findings (editor: of this trial) demonstrate that imetelstat rapidly decreases circulating MM CSCs. In addition, several patients experienced delayed, but sustained, clinical responses as measured by standard criteria. Therefore, imetelstat may have therapeutic implications for MM and other malignancies driven by CSCs.

(Blood, ASH Annual Meeting Abstracts, 2012 120: Abstract 4898)

Imetelstat Rapidly Induces and Maintains Substantial Hematologic and Molecular Responses in Patients with Essential Thrombocythemia (ET) Who Are Refractory or Intolerant to Prior Therapy: Preliminary Phase II Results

G.M. Baerlocher et al. (2012)

Myeloproliferative neoplasms (MPNs), such as essential thrombocythemia (ET), are driven by neoplastic progenitor cells. Telomerase is upregulated in neoplastic progenitor cells and sustains indefinite replication. Conclusions:

Imetelstat rapidly induces and maintains hematologic responses in pts with ET who have failed or are intolerant to conventional therapies. The reduction in JAK2 V617F allele burden and cytokine-independent growth of CFU-Meg suggests that imetelstat has a relatively selective inhibitory effect on the growth of the neoplastic clone(s) which drive ET and has the potential to modify the underlying biology of MPNs.


Inhibiting telomerase to reverse trastuzumab (T) resistance in HER2+ breast cancer

K.D. Miller et al. (2012)

Preclinical studies have shown the combination of imetelstat (GRN163L), an inhibitor of telomerase, and T results in synergistic growth inhibition and restoration of T sensitivity in T-resistant cells (Clin Can Res 12(10):3184–92, 2006). Here we translate those findings to the clinic with the first-in-man phase I trial of imetelstat+ T in patients (pts) with T-refractory HER2+ metastatic disease.

The combination of trastuzumab + imetelstat is well tolerated and results in decreases in HER2 phosphorylation similar to that seen in preclinical models. Additional biologic correlates and PK analyses are ongoing. Further study of this combination in less heavily pre-treated patients is planned.

(Cancer Res 2012;72(24 Suppl): Abstract nr P5-18-13)

Imetelstat (GRN163L); telomerase-based cancer therapy

G.M. Baerlocher et al. (2010)

Imetelstat (GRN163L) is a potent and specific telomerase inhibitor and so far the only drug of its class in clinical trials. Here, we report on the structure and the mechanism of action of imetelstat as well as about the preclinical and clinical data and future prospects using imetelstat in cancer therapy.