About IMerge Phase 3

[Fishermangents]

Due to the latest changes on the CT site (dd 22 June 2016) there has been some speculation whether or not IMerge actually entered Phase 3. That was reason for John Doe (Geron Message Board at Seeking Alpha) to directly ask Anna (from Geron). Herewith a copy of that Q&A:

QUESTION BY JOHN DOE:

Hi Anna,

Can you please tell me if this trial is in phase 3.

ANSWER BY ANNA KRASSOWSKA:

John Doe,

Thank you for your question.

The Phase 3 part (Part 2) of the MDS study of imetelstat being conducted by Janssen has not yet been started. The internal review of the data from the Phase 2 part (Part 1) of the study is expected to occur in the second half of this year. We have stated that we expect the Phase 3 part of the study (Part 2) to open for enrollment in the first half of 2017, based on a positive assessment of benefit-risk profile from the data from the Phase 2 (Part 1).

I would also like to note that we expect to announce when the first patient is treated in the Phase 3 (Part 2) of the MDS study, just as we have announced the initiation of prior company-sponsored clinical trials of imetelstat.

Best regards,
Anna

Anna Krassowska Ph.D. | Executive Director, Investor Relations & Scientific Communications
Geron Corporation | 149 Commonwealth Drive | Menlo Park, CA 94025
650-473-7723 | akrassowska@geron.com

[biopearl]

Thanks for forwarding this post this Fish and thanks to John Doe for getting the info, I think it helps to bring a dose of reality to the overly optimistic. Confucius said, "all comes to he who waits." bp

[Fishermangents]

Very true it is...

[biopearl]

Fish, I just had a long post fail to post and disappear. This has happened before. I don't think I can recreate it again, but might try at some point. I guess we don't have an archive function where it might have gone to? Do we have a time out I might have exceeded? Thanks, bp

[Fishermangents]

Sorry about that. I am not aware of any irregularities. Maybe an update of the server. I will look for this archieve funtion, but I don't think it will exist on posts in progress that not have been submitted yet. It happend to me also sometimes on other boards. Very annoying. In such cases I make the post in Word or copy it to word once the post gets long.

[biopearl]

This is the essence of my deleted post. I am sorry the other one was lost but it might have been too full of musing on a hot summer night anyway. I was thinking about the MDS study clearly not being in phase III despite the rather misleading presentation on CT site and other listings as so as well. As such we can write off 2016 for anything meaningful and perhaps most of 2017 too for MDS study conclusions, judging by the guidance regarding trial duration given on CT site and Anna's response to John Doe. So back to MF. Since J and J plans to file an NDA for imetelstat in 2017, if they waited for after ASH they would be filing in the latter half of December 2017 which is still within the letter of their guidance. None the less if there is very positive data to present at ASH in 2016 then early filing in 2017 would be reasonable and still in keeping with their stated plans. But of course it is unlikely they will be fully enrolled with full data analysis by then and at some variance with the barebones guidance we have been given. I was thinking about ethics. If you woke up tomorrow with your previous brown eyes, blue, that would be a miracle and a scientific impossibility and no p value could be assigned. If you gave one hundred brown eyed people a drug designed to change eye color and one woke with blue eyes (spice?), it would be science not a miracle and some statistical analysis could be applied (the other ninety nine people not withstanding). If spontaneous reversion of fibrotic bone marrow to normal is an impossibility without imetelstat, and that starts happening well before the study's end, at what point must a study stop for ethical reasons? Buried in the secondary end points are assessments of CR PR and CI, primary end points being spleen and symptoms. But these secondary end points are the most important and reflect disease modification. At what point do responsible investigators say that a drug is doing the impossible and causing normalization or improvement in symptoms, bone marrow, spleen and the statistical likely hood does not require 200 patients to prove the impossibility of a spontaneous miracle? A responsible group of investigators, and a responsible FDA can not overlook this if it happens. Ethically they can not, must not. Given the number of enrolling sites, and short time to response in many cases, conclusions could be drawn before ASH 2016 and made public. This is not what we have been led to believe, so is it misdirection, is it a case of under promise and over deliver or do the investigators really believe it? bp

[Fishermangents]

Hi Bio, thanks for your interesting mail. You hit various important points.

MDS Phase 3: we now have the email from Anna that cuts things short. It doesn't exclude any potential earlier ending of the trial, but today no concrete evidence points to that.

The ethical part is complicated as there are two ethical issues which can be at odds with each other. One is that medicines that could safe life should be accessible for patients as soon as possible. The other one is that industry and regulative authorities shouldn't put vulnerable patients at extra risk by keeping a tight eye on the safety aspects during development. Things can go wrong at the latest stage (see pacritinib, fedratinib) or even after a drug is approved. Both these ethical elements have been translated into procedures and processed which we have developed as a society in order to meet with both matters. There are the fast track and OD programs. Imetelstat already has ODD, so we may see some kind of fast track in addition if data look convincing (safety + efficacy). But then we have the standard protocols such as Phase 3 testing, which is largely to balance safety vs efficacy. The FDA takes oversight. In addition there is the DMC, which we have discussed before. This is another mechanism for not only to look into the safety of a trialed drug, but also has the potential of being instrumental in bringing a new drug to the patients faster. It could be that for the oversight there may be an emphasis at safety. The FDA can't be blamed if a patient got a deadly disease, but they do get into trouble if a new drug makes patients sicker than the already are, while the FDA could have prevented that. Ethics and industry don't go well together, while human biology is extremely complex. That's why these oversight procedures take so much time and why getting a drug to the patients faster is such a difficult process to take.

What could have caused imetelstat to need a bit more time than other new drugs is that there is a new MoA. In addition, telomerase and telomeres are about life and death at the same time. The medical community may have needed a bot more time to see that imetelstat doesn't harm healthy cells and organs. The fact that the number of test sites have been growing pretty fast could indicate that the medical community has a level of confidence.

We may not see interim data at ASH2016 already. But imetelstat already has ODD so we should be ready to see some kind of fast track any moment now, if it only was for the 21% of CR's we have seen before. Business and ethics do not always go well together. Let's be confident that in case of imetelstat things come together nicely.

[Fishermangents]

Here the viewpoints of Greg_E (alias Analyst X), posted at SA:


Gerg_E:
This is the sequence of events I see as most likely the reason for the change on clinicaltrials.org: (hereafter abbreviated CT.org)

1) Trial listed as Phase 2/3 on CT.org during active recruitment for Phase 2.
2) Once Phase 2 recruitment ended, Phase 2/3 designation changed to Phase 3 because they are actively recruiting patients for a potential Phase 3.

Remember at the annual meeting, when Dr. Scralett talked about how CT.org is a website primarily to relay information to patients? Well, once Phase 2 was fully enrolled, from a patient-information standpoint, the relevant information for patients is that recruiting is going on for a potential Phase 3 expansion of this trial. If Phase 3 does begin, they are going to have to find 170 patients, and it makes sense to me that Janssen would be wanting to get as much groundwork done as possible to get a head start anticipating the beginning of Phase 3. We are still seeing trial sites open, even though we are all but certain that they've had the 30 Phase 2 patients dosing for some time now. And it is very useful information for patients- if you or a loved one had MDS, wouldn't you want to know that a Phase 3 trial might begin in the next 6 months, and that if you act now you might be able to get you or your loved one enrolled for treatment right at the start of it if it does indeed take place?

Look how long it is taking them to fill the MF trial. I think the reason CT.org shifted to having IMerge listed as Phase 3 is because Janssen is very much actively recruiting for Phase 3 even though it has yet to be green lighted by the data coming from Phase 2. I think this speaks volumes about Janssen's readiness, and also shows that they feel the chances of Phase 3 taking place justify spending resources to actively recruit patients before the Phase 2 results are known. By starting now, they will be able to enroll Phase 3 much more efficiently and significantly quicker than if they waited to begin recruiting patients until after the review of the Phase 2 data was complete.

================

So far Gerg_E. However, there is one interesting thing. If you look back into all the history of changes on the CT-site you will see that 'Phase 3' was already mentioned from day one that IMegre is listed. The funny thing is: I am TOTALLY sure it has been 'Phase 2/3' before. So what happended? Am I wrong? If not: why is there no history of that change?