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).
Two legitimate ASCO-Imetelstat-Tefferi-2016 poster sites: imetelstat.eu & Geron website (investors/events/past events).
JNJ is in full control of the trials and the release of information. JNJ and the FDA work together. IMET has passed all hurdles for new approvals (safe, unique, remissions, disease modification, unmet medical needs, saves lives).
There is more to come with all good news and no bad news on the road to ASH-2016 (follow-up to ASCO-2016, journals like the NEJM, other health conferences, JNJ's trials sites in 12 countries, new approvals worldwide beyond ODD, etc.).
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.
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 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.
No body on this board thinks that IMET will be denied advanced approvals by the EMA and the FDA. JNJ knows what they are doing.
There is no question that IMET works. ASCO focused on IMET, and patients' needs now ("unmet medical needs"). IMET meets all criteria for advanced approvals. Mayo Clinic (Dr. Tefferi) had remissions and disease modifications never seen before (MF). JNJ has confirmed that study and has expanded the trials (near 100 worldwide, MF, MDS, with AML coming).
Various descriptions of Imetetstat: 1. transformative cancer drug, 2. unprecedented remissions, 3. disease modifications never seen before (blood cancers), 4. saves lives, 5. safe to use, 6. enhanced effectiveness in combinations.-- (Previous)
This is an outline of Imetelstat as part of any cancer program and Joe Biden's "cancer moonshot". Of course the FDA also knows this with all of the details. The "IMET Story" is almost complete. All that is needed is advanced approvals from the FDA or anyone of the 12 ASCO listed countries.
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
JimPier---This is directly from the poster:
"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. "
I am interested in the medical science, which appears to be solid (Nobel Prize, Mayo Clinic Pilot trials, JNJ continuing trials). Geron's PPS is in a different universe (hedge funds, manipulation, etc.), but someday the two will merge. One has to believe that JNJ knows what they are doing.
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.
There is no negative news about Imetelstat (even in the rumor mill). With only positive news and "unmet medical needs", it seems to me that the FDA and the EMA approvals are a given. I see no reasons for advanced approvals to be withheld, but no one knows JNJ's plan for platform (blood cancer) approvals.
Naked shorts have had a feast with Geron's PPS. IMET has already been proven to be in a class by itself (remissions, safe, disease modifying, cures) for many types of blood cancer. Yet the PPS of Geron has been in the dumps, mostly due to hedge funds and naked short sellers. Geron will benefit from this Supreme Court decision.
Tefferi and associates are in Chicago, from all over the world, to talk about Imetelstat, not to sightsee. I believe they will have something new and serious to present. We will know tomorrow.
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.
From the Abstract---Imetelstat fills the "great unmet need for effective therapy" in a platform of blood cancers. That is the unescapable conclusion in the abstract. JAK is not effective; IMET is effective.
From Abstract: TPS7079
"Background: 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."
From abstract---Emphasis on "great unmet need for effective therapy" that can only be filled by Imetelstat (IMET). This looks like the evidence that everyone needs (approval agencies worldwide). --previous
The FDA is legally bound to provide for "unmet medical needs" that IMET clearly provides (blood cancers--safe, remissions and life saving). That is the major consideration at ASCO. JAK fails the test; IMET does not.