ImetelChat

Good Day to all from your board moderator, biopearl. New members please don't forget to register or you can not post. Please do post and foster relevant discussions. Posts must be pertinent and avoid ad hominem attacks.

A few thoughts on the EHA presentation. I have not actually heard the presentation (does anyone know where it can be accessed?) but reviewed the slides and the PR. I think there is more here that might be gleaned with a little digging so I am throwing out some observations for board review and critique.

Silde 8 is of particular interest to me. "Absolute change in transfusion amount in best 8 wk interval." If You look at the slides, clearly the results are dramatic with marked improvements transfusion requirements, especially in lenalidomide naive, non 5 del q patients, but the slides don't indicate who is who. This is what the new 25 enrollees will be looking at. The bar was set to look at patients with greater than a 4 unit tx requirement in an 8 week period. One patient responded within days. Median time to TI was 8 weeks--pretty quick. What we have not looked at or discussed are the "clear bars" on slide 8, that is those that are listed as no response. Well yes they did not go from >4 units to 0 as those that are in the green and orange and blue bars, those were dramatic. But look at the clear bars, there are 10 more patients here. To my eye they went from 3 units to 0 (4 patients), 2 units to 0 (4 patients) and from 2 units to 0 (1 patient) in their best eight week evaluation. These are ten more patients that appear to show improvement but are not counted as successes. Had the pre specified bar been set 3 units or 2 units the overall story would be even better. But the bar is pretty high and tells a convincing story. On the other end are 2 pts with no change and one that got worse. I don't think the clear bars should be ignored even though strictly TI was not achieved with a 4 unit reduction. But am I interpreting the slides correctly to suggest that these patients still achieved TI but just started with a lower tx requirement? Please let me know what you think. Best Regards, bp

Bio, so glad you are keeping this site going. You are one of the few that understands what
Is really happening. Your insights are very much appreciated. Some of us have minor understanding
Of the science. So sorry to hear about Fishman, he was truly one of the good guys.
Thanks for your expertise in a really complicated science
Ucj

Hi biopearl,

I'm traveling and only have a second to post, but my thoughts run parallel to yours. I'm not looking at the data now, but when I did my conclusion was that it could be deduced from the data that was released that the transfusion burden was substantially reduced even among those patients that did not generate an 8 week TI. So what you are looking at, patients who did get to 0 from a TI burden of less than 4, and the data I was looking at, deducing a ballpark percentage of the reduction in transfusion burden in patients that didn't achieve an 8 week TI from the data they did release, lead to a strong likelihood of there being a benefit for a large percentage of patients in the trial. My take is that the substantial reduction in transfusion burden is meaningful in many patients in the trial, even if it is particularly meaningful so far in the naive non 5 del q patients.

Best,

Greg

Ucj, it is my pleasure. I hope we can get an active vibrant board going.

Greg, thank you for responding, if indeed we are looking at this correctly and I think we are, taken as a whole if only two patients did not respond at all and one patient got worse we are looking at over a 90% response rate. Granted a full 10 patients did not reach the 4 unit cut point but they did improve. And they improved enough to warrant our attention. How this all remains under the radar is astounding to me. bp

biopearl,

I share your astonishment. It is beyond my comprehension that the number of patients benefitting in the MDS trial isn't the real headline from the standpoint of a potential treatment. It's a fact that high transfusion burdens lead to poor outcomes. All the evidence so far is that Imetelstat is significantly reducing this burden even among patients who aren't achieving the 8 week TI. The good news is Geron is committed to P3 IMerge as long as the 25 new naive non 5delq patients show results consistent with those in the trial already,- and as far as the reduction in transfusion burden goes, I think it is exceedingly unlikely that they regress from the data we already have from the first 32 patients treated. In fact, they are very likely to push the percentages up, because the naive non 5delq subgroup the new 25 patients belong to in all likelihood does have a higher likelihood of responding to Imetelstat than the first 32 patients taken as a whole. So I think we are looking at a 55-60% reduction in transfusion burden in the first 57 patients enrolled in IMerge, with 38 of those patients coming from the naive non 5delq subgroup. That, to me, is a portrait of meeting an unmet need.

Furthermore, the 8 week TI numbers in a small sample size are subject to a higher variation than the overall transfusion burden reduction in the whole trial patient population because someone might miss becoming an 8 week TI by just a few days, so I think the overall reduction in transfusion burden is a truer signal of efficacy than the 8 week TI numbers. As long as Imetelstat continues to dramatically reduce transfusion burden, I don't see how it can continue to be ignored. If we are looking at 60-75% reduction in tranfusion burden in the 38 naive non 5del1q group after the data from the new 25 patients is in, and if a placebo controlled IMerge P3 then demonstrates this beyond statistical significance, then I think this benefit will become available to patients.

Best,

Greg E