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.
Myelodysplastic Syndromes (MDS)
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
2016 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #67a)
J Clin Oncol 34, 2016 (suppl; abstr TPS7079)
Author(s): Ayalew Tefferi, Naseema Gangat, Dietger Niederwieser, Jan Van Droogenbroeck, Maria R. Baer, Jean-Jacques Kiladjian, Ronald Hoffman, Guido Finazzi, Francisco Cervantes, Jason R. Gotlib, Shireen Sirhan, Jane Apperley, Angélique Langlois, Ying Wan, Laurie Jill Sherman, Souria Dougherty, Faye Feller, Olatoyosi Odenike; Mayo Clinic, Rochester, MN; University of Leipzig, Leipzig, Germany; AZ Sint-Jan AV Brugge, Brugge, Belgium; University of Maryland Greenebaum Cancer Center, Baltimore, MD; Hôpital Saint-Louis & Université Paris Diderot, Paris, France; Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY; Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Stanford University School of Medicine/Stanford Cancer Center, Stanford, CA; Jewish General Hospital, Montreal, QC, Canada; Centre for Haematology, Imperial Collegel, London, United Kingdom; Janssen Research & Development, LLC, Raritan, NJ; University of Chicago, Chicago, IL
The markers and indicators (ODD, NEJM, ASH, AACR, ASCO) are clear as the trials expand in scope and depth. The "dots" are all coming together with continuing good reports and no negatives as IMET goes from single use to various combinations and cocktails. The research is just beginning, but IMET has already demonstrated a good safety profile, remissions and cures (ET, MF, MDS, AML pending) as a vital part of the cancer-moonshot. IMET is transformative (JNJ).
Safe, Saves Lives, Unique, Needed Now. The FDA is already onboard. JNJ is holding back because they want a "clean-sweep" or platform worldwide for all blood cancers (ET, MF, MDS, AML, + other cancers). ODD in the USA and EU is all that JNJ (Janssen) needs for now to establish IMET as an important medicine.
As Imbark and Imerge (MF & MDS) proceed, there has been no mention of new remissions. That was the core of the Mayo Clinic (Dr. Tefferi) trials. The trials are moving on with AML being added. There were no questions about remissions. There do not appear to be any new safety related problems, and all trials appear to be on schedule, and expanding. JNJ and the FDA have not spoken. Patient's needs are the #1 consideration, and IMET works for some, but not for all (alone). Combinations are being considered for improved results.
JNJ (Janssen division) knows everything that is now knowable about Imetelstat (IMET). That is the only source of information that is now completely credible. I am convinced that they would not continue with these blood cancer trials unless they knew that IMET was save, effective and a primary cancer research tool. JNJ has called IMET a transformative drug and a platform medicine.
They have not called it a "miracle drug". The potential "miracles" seem to be in projects that are just getting off of the ground (cancer vaccines, death of cancer stem cells, combination drugs, new science). JNJ, for the most part, has been silent about IMET, but I am hopeful that is about to change with the AACR (April 19, posters 2731 & 2732). JNJ controls the future of IMET, and the information in the public domain. There is nothing else. The Mayo Clinic MF data was good, but the investment world and the FDA are looking for confirmations and new trial results to remove any lingering uncertainties.
The evidence is overwhelming, that in the first instance, (blood cancers--ET, MF, MDS, AML, combinations) that IMET works (remissions and some cures), meets the required safety profile, and is needed now by patients all over the world to save lives. The FDA and the EU have both granted ODD status, and as far as I can tell, must grant full approvals post haste, based upon the trial history of IMET. In addition IMET is now a major research tool for all cancers, including cancer stem cells, solid tumors and cancer vaccines. JNJ (Janssen) controls IMET (trials, manufacturing, distribution, information release) and is now speaking about this medicine (trials, potential) at public forums (AACR, ASCO). Terms like "transformative medicine", "platform medicine", and "tantamount to a cure" are not to be taken lightly.
The JNJ Chronicles about cancer and IMET are yet to be published. They will contain the analyses of the massive about of information that is currently being collected in extensive worldwide trials (blood cancers, solid tumors, combination drugs, cancer vaccines and beyond). The AACR (April 19) will be the basis of one of the early chapters. This information will be an important cornerstone for Joe Biden's "cancer-moonshot". The JNJ-Mayo Clinic-Geron associations will be featured.
"Because of its pivotal role in aging and cancer, the enzyme telomerase has become the focus of drug development efforts for anticancer therapeutics, the goal being inhibition of telomerase, leading to a decrease of telomere length, resulting in cell senescence and apoptosis in telomerase-positive tumors.
Approaches to telomerase inhibition have included small molecule inhibitors, antisense oligonucleotides, immunotherapies, and gene therapies that target the hTERT or the ribonucleoprotein subunit, as well an autologous hTERT-pulsed dendritic cell-based vaccine under development by BioTime subsidiary Asterias.
Asterias’ AST-VAC1 and AST-VAC2 are dendritic cell-based vaccines designed to immunize cancer patients against telomerase. AST-VAC2 differs from AST-VAC1 in that the dendritic cells presenting telomerase to the immune system are produced from human embryonic stem cells instead of being derived from human blood.
Geron’s Imetelstat, a lipid-conjugated 13-mer oligonucleotide sequence complementary to the RNA template of the telomerase, directly inhibits the enzyme’s activity. Geron has partnered with Janssen Biotech to develop and commercialize Imetelstat worldwide for all indications in oncology, including hematologic myeloid malignancies, and all other human therapeutic uses. Under the collaboration agreement, Janssen is responsible for the development, manufacturing, and commercialization of Imetelstat worldwide. On September 16, 2015, Geron announced the dosing of the first patient in a Phase II trial to evaluate Imetelstat in patients with myelofibrosis.
In a recently published New England Journal of Medicine paper by Gabriela M. Baerlocher, M.D. and colleagues, it was reported that Imetelstat showed disease-modifying activity in Phase II studies of myelofibrosis and essential thrombocythemia. Among thrombocythemia patients, patients achieved a hematologic response, with the majority achieving a hematologic complete response."
The credibility here is A++. Mayo Clinic and Janssen (JNJ) plus some of the preeminent cancer researchers in the world cannot be wrong about Imetelstat at this late date. There are 101 trial sites for MF and MDS with new trial sites coming for AML ASCO will continue the good news, with Dr. Tefferi and Janssen in control of both IMET and the information stream.
As I understand it, the FDA has a legal obligation to approve IMET immediately, if there are unmet medical needs and a safe, life-saving, effective, unique drug available. IMET meets all of those criteria, so why isn't the FDA doing what it is legally obligated to do?
JNJ/Janssen is in complete control of all IMET concerns (trials, analyses, FDA interaction, manufacturing, distribution, public information, etc), so only JNJ can answer that question. ASCO may provide the answer for new approvals beyond ODD in the EU and the USA.
(3/22/16, AP)--Terrorism expert Malcolm Nance said Trump’s “bluster” in the wake of Tuesday’s attacks was hampering U.S. intelligence and the armed forces.
“Donald Trump right now is validating the cartoonish view that they [Islamist militant groups] tell their operatives and that they tell their terrorists,” Nance said. “That the United States is a racist nation, xenophobic, anti-Muslim, and that that’s why you must carry out terrorist attacks against them.”
Nance said that type of rhetoric is detrimental to global counterterrorism missions.
“There are intelligence officers right now that are going to have to contend with their partners over what’s being said during the U.S. presidential race. It’s irresponsible, and it needs to stop.”
Cancers in the form of fascist dictators have risen before. Trump is most like Mussolini in terms of his arrogance, emotions and insanity. The war is on against the "Cancer-Trump", as well as against human cancers by IMET. Trump must be stopped before it is too late. The Republican party is now in his control.
This is the target and contains the solution: Cancer stem cells are small populations of cells within tumors believed to be responsible for initiating tumor growth, recurrence and metastasis. Cancer stem cells are capable of indefinite self-renewal because of high telomerase activity, and can differentiate into all malignant cells found in a particular tumor type. Cancer stem cells often show resistance to standard therapies resulting in renewed proliferation and differentiation, leading to disease relapse.
The massive "amount" of IMET information will be statistically significant. That was one of the complaints with the Mayo Clinic data (too small of a sample). The Mayo Clinic trials were good, and I expect similar results from the JNJ trials. They will publish the results (good, bad or indifferent). Considering the expansion of the trials, "good" is the likely outcome. This quarter should be important, as the data starts to flow. The mismatch between Geron's PPS and IMET's successes should begin to correct itself (assuming "good" results).
My premise is that Imetelstat is being supported by a team: Mayo Clinic (world's top, perhaps #1, research hospital, JNJ/Jannsen (world's top, perhaps #1, oncology drug company, Geron (a small research biotech company that realized IMET's potential and brought Mayo and later JNJ into the loop. All three are important, but at this point in time JNJ is carrying the ball through the very complicated approval process that is being carried out worldwide (medical, scientific, legal, applications).
The safety issue is mostly behind us (dosage is always an issue), and observed effectiveness is expanding beyond the blood cancers. JNJ knows all (data, patients and trials) and continues to be fully supportive. JNJ is in charge.
There is no short term correlation between Geron's battered PPS (market driven) and IMET (medical successes), but longer term they will correlate. JNJ is not pulling back. The time is near as the new trial data is collected, analyzed, published, and explained at medical conferences. This quarter (April, May, June) will reveal much of that.
Look at the ASCO title: "--previously treated with Janus kinase (JAK) inhibitor--"
The JNJ worldwide trials are designed to determine several things, including a comparison of IMET with JAK--the subject of Dr. Tefferi's talk.
1. Compare the effectiveness on the symptoms (spleen, general improvements)
2. Compare disease modifying properties'(full and partial remissions, tentative cures--chronic and full)
Dr. Tefferi, as the principle JNJ investigator, will tell about the progress of the JNJ trials, with JNJ's full permission. He also maintains his Mayo Clinic position.
Previous--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.
Ayalew Tefferi, MD - Presenter •
Poster Board: #67a
I hope and think that Dr.Tefferi's presentation at ASCO in early June will be significant using old data from the Mayo Clinic trials and new data from the Janssen trails, since he was and is the principle investigator at both, and certainly a decision maker.
No person in the world knows more about Imetelstat than Dr. Tefferi. By ASCO, there should be enough data collected, with analysis, to make some very definitive statements. The abstract indicates that there will be a comparison between IMET and JAK.
IMET is proving itself in the blood cancer universe (ET, MF, MDS, AML, beyond). It's potential is just being realized as a cancer vaccine for solid tumors and cancer-stem-cells. The safety profile is good in all of these situations, as far as I can tell. It is unlikely, considering the time of usage and the number of patients, that there will be any new safety issues, other than adjusting dosages and new combination drug interactions, to worry about. JNJ and the FDA certainly know this.
Medically and scientifically, IMET seems to be all set. JNJ knows something that they 'ain't' telling yet. We are waiting for ASCO and Dr.Tefferi.
JNJ would not have started trials on a 2nd blood cancer (MDS) unless the MF trials fully met expectations.
ODD status was applied for and granted to Janssen (JNJ), not Geron. Janssen (JNJ) has/will apply for all IMET approvals (FDA and worldwide). Geron was an important factor in the development of IMET, especially in the ET phase. Mayo Clinic was the decisive factor in the MF phase. Janssen (JNJ) is in control of the worldwide phase for all blood cancers now, and all cancers in the future (including cancer stem cells, solid tumors, cancer vaccines, etc.). Geron's PPS is a derivative of Janssen's IMET successes.