ImetelChat

So here we are beyond the 24 week mark with the suspended study and patients are continuing to receive drug. Excluding the 4.7 group which has presumable crossed over to a higher dose there can be no doubt that Geron/Janssen have the data they said they wanted in the original 9.4 group. The Clin trials site and FDA files emphasize that the end points are straightforward: Spleen size and symptoms. That they didn't have these at 12 weeks is apparent. If they had it at 24 weeks I think they would be bursting to tell us. Conclusion? They don't have it. It is so disingenuous to not just say, ok we need another 12 weeks (we will see you in Q2), or so since the disease is so severe and it truly takes a long time to repopulate the bone marrow. I'd be fine with that and Scarlett has stated it. But really by saying we will talk to you in Q2 is just plain wrong as this is material information. An error of omission is equal in severity to an error or omission or at least that's what my scoutmaster taught me and I continue to believe. At least they haven't shut the study down so it is clear they are hoping for the desired end points but need more time. Fine, take more time, just don't make believe we don't know that thats what you doing. Have a little respect and consideration for your investors. Thats my holiday rant for now. Oh, and no AML study. If we don't see it this week we won't see it because nothing will happen the week between New Years and Christmas. Every year I swear I won't vote for option approval for company leaders. I am thinking this might be a good New Years resolution. Regards, bp

Bio, your observation that we have an omission here regrading the provision of material information is a serious matter. I would suggest to send an email to Dr.S. He probably knows you and will likely read your email. I believe he shouldn't leave such an email unanswered.

From Ligas3 on SA:

"I saw your post about the 24 week analysis. Your time frames are wrong. The 12 week analysis of the first 20 patients is completely separate from the 24 week analysis of all patients in the study, emphasize all. If 20 patients were at 12 weeks in September then they certainly would be at 24 by now. However, the remaining 20 or so in the original high dose may not complete 24 weeks until after the first of the year. Also, I don't know but I would assume they would want cross over patient data at 24 weeks and those patients wouldn't complete 24 weeks until second quarter. This is why I think no one is talking."

From Bio on SA:

"I have thought about your comments and I may be incorrect as you suggest in my timing, if so I apologize and did not intend to be misleading. My understanding is that as each patient reaches first the 12 week mark, and then the 24 week mark they are analyzed on a rolling basis, that is J and J is not waiting for all patients to reach 24 (or by definition, longer) to analyze. That would mean the first group of patients reviewed at the 12 week mark all got there at different times but all would have gotten to or exceeded the 24 week mark by now. My point is that this group should be analyzable now just as they were at 12 weeks. You are correct I believe that of course that would not include all patients enrolled to date. Enrollment probably continued probably up to a time pretty close to the Sept surprise date so those patients data would be looked at only at a later time to reach 24 weeks also. But a substantial number of patients are at 24 weeks now. That is my point. If a significant number have appropriate spleen reduction and symptom reduction then the study should be halted on ethical grounds and so far it ain't happening. As far as cross over, I am not sure what you mean but the 4.7 group (increased to 9.4) will not be analyzed with the original 9.4 group but will be looked at separately. Maybe the 4.7 will be a "primer" who knows."

From Ligas on SA:

"I really don't think they will make any decisions until all patients in the study have reached 24 weeks. Remember that according to response criteria, any response must be held for 12 weeks at least to be considered a response considering all of the first 20 were at 12 weeks in September, there could still be some in that group that are technically just achieving a response now. A patient can't simply have a reduction in spleen volume at 12 weeks and be considered a spleen response. It has to last 12 more weeks. considering that it would take a few doses probably to start showing signs of improvement, it wouldn't be unusual for a criteria defined response (lasting 12 weeks) to technically be defined as a response say 24 weeks later."

I am hereby officially backing away from my comments of yesterday which I admit were not dispassionate. And I am hearted by the updated website. Note the Dec powerpoint company presentation. Ligas, thanks for your response. Fish, yes Scarlett and Anna probably know be by now but I don't think their responses would be any different than the standard company line. Clearly, with the new web site Geron is all dressed up and looking for a date. bp

Alright, I am back in. As I stated on SA, I don't think they are going to say anything about anything until they have 24 weeks of data on the low dose cross over patients after they have been on the high dose for 24 weeks which will be second quarter. Then they will have 24 weeks of data on everyone in the trial on the high dose and over a year's worth of data on the first 20 patients. I expect that if the data is pretty good , they will file for approval with the FDA for the RR population. It does not make any sense that even thought the MDS and MF trials are both not recruiting, that the MDS trial is still listed as recruiting and listed on JNJs website but the MF trial is suspended and not listed. I don't believe they have any intention of opening for further enrollment the RR MF trial.

I’m not quite sure how to intelligently ask this question. (When one asks very basic questions it’s easy to appear idiotic.) Whatever. Here's my question:

Is it easier to gain approval from the FDA w/ regard to a new drug without which patients face a future with no treatment options and a very short life span?

I’m referring to this: In the ASH PR "Among patients who failed or discontinued frontline ruxolitinib, the median survival was seven months, which underscores the need for new treatment options for this disease." http://finance.yahoo.com/quote/GERN/community?p=GERN

Does this fact lower the bar to obtaining FDA approval w/ regard to the present MF trial of IMET?

In other words how many MF patients need respond positively to the drug in order to win FDA approval?

Here’s the corollary to my previous question: How many MF patients in the present trial have to respond positively to IMET in order for JNJ to wish to continue the present partnership w/ GERN and bring the drug to the market? What magical number makes this enterprise worthwhile and profitable to JNJ? (Yeah, I know. These questions are very broad and not subject to precise answers. These are, however, the type of questions that run through my mind late at night when attempting to better understand my investment in GERN.)

Hi Sargasso, these are all very good questions. It seems JnJ/Geron chose the MF R/R because no alternative exists as you say. That means that any positive result on these patients will be a 'victory' on BAT. I think JnJ/Geron will also look to the kind and depth of the response, in addition to the symptoms the are listed as primary criteria. The question on how many responding patients are needed in order to make it worthwhile is difficult. I think they will use the MF R/R group to get approval because of the unmet need. However, once approved, the bigger fish to catch will be MDS and MF Frontline and - who knows...- AML and CML (in some combo?) later down the line. With already an approval in the pocket additional trials and approvals may move quicker. I expect various things to unfold during 2017. Let's wait and see, while trying to understand the deeper meaning of the things we see and hear.

Sargasso, the FDA is inscrutable or they would have already approved. If I had to guess I would say they would look very favorably on a 20% CR/PR response. CI on top of that is gravy. bp

I’m wondering if there was not another practical reason for the structure of the present GERN/Janssen MF trial: lack of patients who have not been previously treated with Jakafi (ruxolitinib). As observed in this dated article concerning momelotinib:

“Gilead has acted in all speed, rapidly opening Phase III trials. One major obstacle: Patients previously treated with a JAK inhibitor are barred from participation in the trial. In this post-Jakafi era those patients aren’t easy to come by.

“We just have to wait,” says Jun. “We wait for the newly diagnosed patients. The physician has to decide the patient is a good candidate for JAK inhibitor treatment. It’s hard to find myelofibrosis patients in the West who have not yet received a JAK inhibitor.”.....

“Getting out of the starting box, launching its critical Phase III trial of Momelotinib, required analyzing legacy data, writing up protocols, opening sites, clearing various institutional and National regulations… and, hardest of all. recruiting patients. Most patients needing a JAK inhibitor were intermediate or high risk MF and many were already on the Incyte drug. And with FDA-approved Jakafi readily available, underwritten by insurance companies and Incyte, a patient’s incentive to take a chance on clinical trial was lowered.”

https://mpnforum.com/ash-2014-dr-susi-j ... melotinib/

I’m just thinking out loud. The point may or may not be valid. But perhaps the present GERN/Janssen MF trial is structured exactly as it needed to be.

I don't believe they would have had a problem recruiting newly diagnosed non-JAK patients. Especially with people like Dr. T suggesting that patients should try an experimental drug prior to JAK. It seems to me the current trial was chosen because it's easier and quicker to prove that Imet is better than nothing as opposed to Imet it better than JAK. It seems like the quickest path to approval ... however I am a bit worried that the patients they are treating are too far along the disease path to demonstrate signs of efficacy similar to the Mayo trial.

I mean not to belabor the point, but suppose an ideal MF trial of IMET involved intermediate or high risk MF patients not previously treated with a JAK inhibitor…so this would involve a direct comparison between IMET and Jakafi. How are you going to find such patients since so many of them are already on, or have already failed, Jakafi? How long would it take to locate a sufficient number of such patients in order to conduct the trial, and what is the total amount of time this recruitment would take?

So my question is how should have GERN structured the present MF trial given these real world limitations? What is the MF trial GERN should have run but did not?

It seems to me that GERN/Janssen structured the present MF trial in order to gain a direct route to approval in the shortest time possible. That, I think, was the objective. But perhaps I'm missing something. Or just don't get it. The latter being entirely possible.