ImetelChat

The recent article of Senyak is a sad landmark in the existence of the MPN Forum. Being a forum for imetelstat I believed that such a blatant attack could not go by being ignored.

Whatever Senyak's agenda is, it is a disgrace that he is trying to prevent suffering patients with no options from participating to trials of imetelstat. And how is he doing that? Just like a pseudo scientist with a big ego and a hidden agenda would do. For Senyak that obviously means emphasizing negatives that are not relevant (e.g. failed tests of the past) and ignoring successes in current tests in MF and MDS, including the promising pre-clinical results for AML and the 3x ODD.

His article is showing a known strategy used by people who deliberately want to put a person, organization or a product into a bad perspective in order to do harm.

The first part of the strategy: using old information. Geron already decided not to pursue the ET indication, so this is old news about an obsolete path. The clinical hold was lifted, so that is old news too. It is clear since the lifting of the hold, that the main side effects are manageable and reversible. Mr. Senyak however uses these old facts without mentioning that these issues are already addressed and being tested with the blessing of the FDA.

The second part of the strategy is ignoring the positive fatcs. And for imetelstat there are many. However, Mr. Senyak refuses to admit that imetelstat is still the only drug that has caused complete remissions in MF, including the full clearing of the bone marrow. Instead he tries to keep suffering MF patients away from imetelstat and to slow down the enrolment process of the trials. More patients will die because of his advice. Another fact he ignores is the progress of the ongoing trials. Currently imetelstat is being tested at 110+ sites around the world. The official feedback is that the trials are progressing according to plan and that the involved scientists are positive. Yet, Professor Senyak believes he should warn patients about the side effects of imetelstat, as if all those doctors involved aren't already fully aware of that. The side effects are in the public domain. What could the opinion of a pseudo scientist like Senyak add to that? Or could it be that Mr. Senyak is just heavily over estimating the value of his own opinon becasue he is not seeing the limitations of his intellectuel potential?

Part 3: the use of framing methods, which are not based on facts or which are simply not true. Senyak is selective and plain wrong in his judgement regarding the hyping of imetelstat. While he himself has strongly hyped Jakafi, imetelstat has never been hyped by patients, nor by the medical community and certainly not by Geron. On the contrary: the investment community is continuously complaining about the fact that Geron is not promoting imetelstat sufficiently. In the meanwhile, Senyak (mis-)using the MPN Forum to promote his CRISPR activities is a perfect example of hyping. We all know that Dr. Tefferi has publicly critized the hyping of Jakafi, which includes prominent hypesters like Senyak himself. Tefferi has always been very cautious about imetelstat and he has always stated that larger tests are needed to prove imetelstat’s efficacy and safety.

Part 4: ignore clear signals from the scientific community. Senyak prefers to ignore that the current poster presentation at AACR is co-authored by 18 (!!) scientist, including some of the most respected in the world. Instead, he cites the negative experiences of a single patient from a long time ago and lets a single and unknown doctor speak out his personal concerns. Senyak also tries to put aside the important finding that imetelstat has reduced the JAK2 and CALR allelic burden in these ET patients. It also seems that Mr. Senyak doesn’t want to mention the ODD status of imetelstat for MF and MDS.

My impression is that this man is suffering from a big ego, a big mouth and pseudo science. A dangerous cocktail. But now he has proven to be a slick manipulator too, over the backs of suffering patients. With his article about imetelstat he has disqualified himself as being an independent platform for MPN patients. It is getting time that the MPN Forum is being taken over by people who actually care for patients instead for their own ego.

I would like to conclude with Senyak’s suggestive and highly manipulative question: “Is the imetelstat trial now recruiting more likely to help or harm?”. Because Mr. Senyak implicitly gives the answer to that question himself (like he always does), I have some questions for Mr. Senyak in return:
- How can a pseudo scientist like you already know the outcomes of the ongoing trials? What other information do you have apart from the single patient’s report and the single, unkown doctor’s statement who hasn't seen all the data from closeby?
- What drives you to prevent dying patients from undergoing a trial with imetelstat, the only drug so far that has achieved complete remissions and significant response rates?
- Are you aware of the responsibility you have taken towards these patients by suggesting that they should NOT participate to the imetelstat trials?

Here are some comments on Senyak’s article collected from other forums:

“His tactics certainly are not helping patients in need. Just to collect his paycheck. What does that make him?”

“Pfew, just read the Zhen article. It made me want to puke all over my screen. Toxicity has always been a "problem" and I know we had the infamous Hold and then the full release but still, it always bother me when you find very dedicated people who will do whatever it takes to put something to the dirt.”

“Wow looks like a desperate attempt to what avail ? Such rehashing of old rumors is not about to halt the Janssen trials and the data will speak for itself. I love how these shills keep using the bogus FDA holds to promulgate their misinformation.”

“Its a shame.. I would love to hear a good thought out bear case but this was all the same information (besides the baby powder photo) that was out for years. The article was just a good ole copy and paste. I like that it doesn't have a date on it, and comes out the same day a antisense drug has toxicity issues.”

“To me it is proof of a deliberate attempt to manipulate spreading old rumors -- why ? There really is no bad news about Geron for the last 3 or 4 years that is REAL ! Any negative spins are just that--spins with a motive!”

“Well Zehn must be a little out of whack - his article doesn't mention that the MOA for Imet doesn't involve a TLR (toll like receptor) in the innate immune system as suggested by Greider. DD my hinie...”

Okay. He is criticizing the ET trial. Fine. But why does he advice patients not to participate to MF or MDS trials? This link is completely missing. I am totally lost on this guy.

I did check the ET trial report. The investigators were:
United States:
McDevitt, Michael / Odenike, Olatoyosi / Snyder, David / Spitzer, Gary / Verstovsek, Srdan
Germany:
Ottmann, Oliver, Rőth, Alexander
Switzerland:
Baerlocher, Gabriela M. / Daskalakis, Michael / Oppliger Leibundgut, Elisabeth

Via imetelstat.info you can link to the abstract, then to the full text and then to the appendix.In the appendix the terminology is explained. Here some takes:

=======
"The overall rate of hematologic response was 100%"

Hematologic response = HCR + HPR

Hematologic Complete Response (HCR / 89%) = Normalization of platelets (≤400x103/µL) maintained for at least 4 consecutive
weeks, in the absence of thromboembolic events

Hematologic Partial Response (HPR, 11%) = Platelets ≤600x103/µL or a 50% reduction in platelets maintained for at least 4 consecutive weeks, in the absence of thromboembolic events
=======
"A complete ELN clinicohematologic response was observed in 17 of the 18 patients (94%), and a partial response was observed in 1 patient (6%)"

ELN “Clinicohematologic” Response = Complete Response (CR) + Partial Response (PR)

Complete Response is:
1. Platelet count ≤400x103/µL, AND
2. No disease related symptoms, AND
3. Normal spleen size, AND
4. WBC ≤10x103/µ

Partial Response is:
In patients who do not fulfill the criteria for CR:
Platelet count ≤600x103/µL or decrease ˃50% from baseline
=======
The this is interesting too:
"In 1 patient, splenomegaly that was palpable at 3 cm at baseline became nonpalpable after the first cycle of treatment. None of the 18 patients had constitutional symptoms at baseline."
===========

So 89% didn't experience thromboembolitic events and had normalized platelets (<400) and 94% had a Complete Response (ELN). I can't find another explanation of these results than that imetelstat has a dramatic effect on the disease. I really have no idea how this can be turned into a negative.

To find the Baerlocher ET report you go to imetelstat.info/clinical, scroll to 2015 and then find "Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia, G.M. Baerlocher et al (2015)"

You can also go directly to the abstract here: http://www.nejm.org/doi/full/10.1056/NEJMoa1503479

Fish, kudos for a trenchant examination of Mr. Senyak's article. You have done a good thing in that your comments may help a potential study patient find a new therapy for a previously hopeless condition. There are always risks with most therapies (a quick look at Jakafi will confirm that!) That Mr. Senyak presents such an unbalanced view of Imetelstat certainly suggests a different agenda (see "Trading Places" where one market is bid up and another suppressed so a turnabout, when it comes is all the more dramatic.) I doubt he is an altruist, unlike yourself who it appears is on a mission to bring up to date, cogent information to the public domain. Dr. T and to a lesser extent Dr. S have been still small voices awaiting the data which will support raising the small voice to a roar. This is the correct and scientific way to proceed. I hope Sergi and company and Dr. Shay and company and others, will also eventually get the recognition they deserve from the scientific community and the public, in leading development of this ground breaking therapy. Your efforts to bring a balanced and accurate view of the Imetelstat story forth may actually affect someone's decision to participate in a study that could be life altering (see below). It is said in the Talmud that he who save a single life, save an entire world. Do not underestimate your rebuttal efforts directed toward Mr. Senyak. We do not know when the still small voice will be raised but to be sure it will not be until there is serious and significant data to justify that. I speculate that the reason Irish is maintaining radio silence is that morally and ethically her personal knowledge precludes any communication as I hope sincerely that John and his cohorts have now long out lived their disease in a way that can be proven in a dramatic and statistically significant manner and she knows she cannot share this information. This is pure speculation on my part but to me her silence speaks volumes. I look forward to a time when she feels she can comfortably give us an update. It is possible that the wall of Incyte will come tumbling down and Mr. Senyak's apparent agenda with it. Regards, bp

bp,

It seems more likely than not to me that the sponsor of GERN’s clinical trials informed Irish not to disclose any further information about the ongoing results of these trials and specifically, the progress of her husband w/ regard to his participation in these trials. It is my understanding that such results are commonly considered a trade secret:

“Pharmaceutical manufacturers have long considered results collected from drugs’ clinical trials to be confidential information or trade secrets, even after submission to the Food and Drug Administration (FDA)…. Pharmaceutical manufacturers, like other businesses, keep many details of their research and development (R&D) secret to gain and preserve a competitive advantage. Traditionally, data they collect while conducting clinical trials have been considered confidential along with other business information…

“Pharmaceutical manufacturers guard most research data as confidential commercial information or a type of intellectual property (IP) called a trade secret. The legal protection that accompanies these designations is central to the current debate over improving drug safety. Drug companies point to the economic value that preclinical and clinical trial data may have for generic manufacturers and other competitors, including those seeking approval of rival products in international markets.” (footnotes omitted)

http://content.healthaffairs.org/content/26/2/483.full

Secrecy is a difficult thing. For the business it is a prerequisite. For patients it can be misleading. For shareholders too. We can just hope that the investigators of new drugs are keeping their integrity. I put a lot of trust in Tefferi, Mesa, Verstovsek, Vannucchi, Kiladjian, Silver, Hoffman, Cervantes, Cantilena, Gotlib, Harrison and others from the same pedegree, and who are keeping a very close eye on imetelstat. That's why I am rather confident: there are many of the world's most acknowledged experts involved in the research. They can't all be simultaneously corrupted. For quite some time these doctors were very carefully when speaking about imetelstat. Until recently they sometimes only mentioned telomerase as a new potential target. But that has changed, as we see that more doctors are speaking about imetelstat in public. Btw: none of them is hyping imetelstat, as far I have seen.

However, there will always be risks involved. We should look into the sings we trust. Senyak is not one of them.