=====================
Previous: The benefits clearly are important and significant. The risks are manageable and reversible.
The Positives:
1/Transfusion independence
2/ Overall Survival Time
3/ Disease modification
4/ Two ways to kill cancer cells (MOA) -- normal cells OK
5/ Off label uses (in combination --- chemotherapy and other promising combinations when approved)
6/ Very good safety profile
7/ KOLs, publications, conferences
8/ Quality of life
The Negatives:
1/ None available that appear medically important
FDA v. Geron
Forum rules
- Comments must be civil and on topic
- Back up claims with evidence/reasoning/sources (posting links is allowed)
- No commercials/harassment/spam
- Comments must be civil and on topic
- Back up claims with evidence/reasoning/sources (posting links is allowed)
- No commercials/harassment/spam
Re: FDA v. Geron
What are the medical negatives? Imetelstat will be approved (IMO). Let's hear what the KOLs have to say about Imetelstat's medical successes.
Re: FDA v. Geron
I was surprised how aggressively the FDA came out of the starting gates (devil's advocate ?). In the morning (March 14th), it appeared that Imetelstat was on the ropes. However, by the afternoon it all turned around and the medicine was approved by a 12 to 2 vote by ODAC. The subject at hand was transfusion independence, but quality of life, overall survival time, and disease modification were all in the background.
There were two negative votes, one from the ODAC Chairperson, which was a surprise. However, there were several blood cancer hematologists on the board, and they were all yes votes. I understand that 97% of all positive recommendations are accepted, so FDA approval of the NDA seems ensured. (Is there an example of a positive recommendation that was not accepted?)
How is ODAC put together? How is the Chairperson chosen?
There were two negative votes, one from the ODAC Chairperson, which was a surprise. However, there were several blood cancer hematologists on the board, and they were all yes votes. I understand that 97% of all positive recommendations are accepted, so FDA approval of the NDA seems ensured. (Is there an example of a positive recommendation that was not accepted?)
How is ODAC put together? How is the Chairperson chosen?
Re: FDA v. Geron
A question for the board:
Has an ODAC (oncology advisory) positive recommendation ever been rejected by the FDA? I cannot find one.
If yes, can you share the case? The 'black-box' issue, while interesting, is not all that important (IMO).
Has an ODAC (oncology advisory) positive recommendation ever been rejected by the FDA? I cannot find one.
If yes, can you share the case? The 'black-box' issue, while interesting, is not all that important (IMO).
Re: FDA v. Geron
Imetelstat is an inch from being an approved medicine by the FDA and others. NO ONE can find an ODAC (Oncology Data Advisory Committee) positive recommendation (March 14th) that has ever been rejected by the FDA. Then off-label uses can be explored including new combinations.
Somewhere over the rainbow partners of various sorts are being considered.
Somewhere over the rainbow partners of various sorts are being considered.
Re: FDA v. Geron
"There were 12 instances where the FDA rejected a product that an advisory committee had recommended approval. Three were reviewed by the Endocrinologic and Metabolic Drugs Advisory Committee and two each by the Oncologic Drugs Advisory Committee, Anesthetic and Analgesic Drug Products Advisory Committee and Psychopharmacologic Drugs Advisory Committee."
Advisory Committee Disagreement With US FDA On Approval Decisions An Increasingly Rare Event
https://pink.citeline.com/PS147536/Advi ... 20approval.
Advisory Committee Disagreement With US FDA On Approval Decisions An Increasingly Rare Event
https://pink.citeline.com/PS147536/Advi ... 20approval.
Re: FDA v. Geron
What i would like to see is the ADCOM votes - how common is 14-0 13-1 12-2 ETC - the cases where the FDA goes against the ADCOM is that where the vote was 8-6 , 9-5 ?
-
biopearl123
- Posts: 1676
- Joined: Fri Jul 20, 2018 5:13 pm
Re: FDA v. Geron
RC, also important here is where all the positive votes came from (every liquid tumor doctor), including an invited specialist. That should give us some reassurance that failure to approve is unlikely.
Re: FDA v. Geron
If 12-2 doesn't hold any weight, then the moon is made of cheese.
Re: FDA v. Geron
I am preparing myself for another delay, to knock the approval back from June.
After reading the updated risk document a few days ago, which detailed numerous ways the FDA could cause a delay, and the ridiculous showing the FDA did in the first half of the odac, I fully expect some shenanigans.
I think there is no doubt it will be approved, but just incase there is a delay, the latest offering covers that cash burn, hopefully.
After reading the updated risk document a few days ago, which detailed numerous ways the FDA could cause a delay, and the ridiculous showing the FDA did in the first half of the odac, I fully expect some shenanigans.
I think there is no doubt it will be approved, but just incase there is a delay, the latest offering covers that cash burn, hopefully.
Re: FDA v. Geron
I don’t think the FDA will deny approval. The drug benefits a subset of patients who have failed ESAs. The agency may restrict the label regarding who can use the drug and for safety reasons. However, I see another issue the FDA may want Geron to address: the lack of data on luspatercept failures. Luspatercept is now approved as front-line therapy for RS+ and RS- MDS patients. More and more of the potential market will be luspatercept failures, not ESA failures. Geron has very little evidence to provide the FDA that imetelstat works in this patient population, as only a handful of these patients participated in the Phase 3 trial. The FDA has a built-in argument against exposing these patients to imetelstat’s side effects without evidence of benefit. The agency may require Geron to conduct a post-approval trial on these patients. And Geron should, or another company will.
Re: FDA v. Geron
It very unlikely that the FDA would reject their ODAC's recommendation for approving Imetelstat. Still we are a bit nervous about the FDAs "devil's advocates" comments (March 14) and the (NO) vote of the chairperson. The FDA has much on its table these days, as their past and future is now being reviewed in the Supreme Court.
==================
Review
==================
Review
These were the no votes (12 yes, 2 no)
2. AC-Ravi Madan(Chair) NO
8. AC-Mark Conaway NO
As I remember some of the no reasons were:
1. Only a subset of people benefitted
2. Unnecessary disease in those that did not benefit
3. No biomarkers
4. Quality of life (feeling better) is too subjective to be considered
However, all agreed that transfusion independence was an important goal.
It was surprising that the Chair voted no. ---- from LWS
=====================
As far as the two no votes, I believe the Chair (solid cancer oncologist) thought too many non-responsers had to go through the initial disease ( cytopenias -- that could be controlled), and there was no benefit to them. I cannot explain the other no vote (the statistician). The Chairperson was a bit out of his field of expertise (IMO).
I cannot find any example of an ODAC positive recommendation being rejected by the full FDA. A 12 to 2 vote is overwhelmingly positive, especially when the 2 no votes were from non-experts in the field of oncology hematology. -- from LWS (Note, 2 cases were found, but we do not know the circumstances -- from CKTC)
====================
Yes, I am troubled that two prominent members of the FDA ODAC, who were not experts in the management of MDS have the voice to impede approval and that the FDA itself did not understand some very basic aspects of how studies in MDS are done and how yardsticks such as CR and PR just do not apply. Thank you Dr. Komrokji and Dr. Savona for setting them straight, but honestly, its the FDA, shouldn’t they already know this? Well, two members of the panel didn’t and perhaps still don’t. We should just take the win and move on. --- from bp
-
huntingonthebluffs
- Posts: 253
- Joined: Wed Feb 24, 2016 12:00 am
Re: FDA v. Geron
I have watched Geron and its stock and have been an investor for a very long time. Certainly not the longest here, maybe even just average. I know there are many old timer investors here that are determined to see this through, many of us well over a decade and some even decades. Most of us know of and have seen the ravages of the MPN diseases firsthand in our relatives and friends, several of our fellow board members have passed due to these diseases and others are still with us. And now here we are again, moving towards another launch pad of sorts for at least the 3rd or 4th time since I’ve been watching.
There has been a lot of excessive confirmation bias here over the years, admittedly including myself. I have been a strong believer since my initial Geron awareness and a very strong believer since Dr. T’s CT efforts at Mayo. I could only guess of course, but I believe the road is littered with FDA (and associated corporate sponsors) shenanigans, both large and small in that time. I don’t think anyone involved in this space over the last decade plus could or would deny the probability of what IMHO is undeniable. And that is after subtracting out possibility of Geron mistakes, execution and judgement failures.
Rationale for FDA administering delays and restricting designations and accelerators might have had some minor justification at times although even then they must cruelly face down most patients who are in their 70’s and have no other options of merit. However, the other side of that coin has the obvious, much more likely intentions, which have real costs to the Geron strategies, as well as investors and obviously patients, tens of thousands that are no longer with us including many family members, friends and fellow board members. Secondary impacts like blood supply, its quality, caregiver time and costs, next tier advancements, etc. have major untold costs. And of course, delays benefit competitors and their investors via stock portfolios, revenue streams and drug pipelines as well as leverage on partnership and B/O costs and the funds to use for M&A on Geron or other pharma’s, etc.
Anyway, for all the reasons that have been mentioned now and over the years, Geron and Imetelstat IMO are finally on the cusp of greatness. Most, maybe all of us, cannot fully comprehend the potential of Imetelstat and associated IP along with combinations and future related research discoveries like malignant cell death being invoked by ferroptosis. However, each successive time we make it to the alter, I believe we have improved likelihood of approval with revenue and relief just around the corner for MDS and MF patients as well as those with other heme malignancies.
Investors are likely due for success as well this time around. And as Charlie Munger would say, most of us only get a couple opportunities in our lifetimes accumulate generational wealth. I personally think this may be one of those times. Yet I know, the possibility is there for further delays and disappointments and the last time our confirmation bias was this high was September 2018 and that didn’t end well. Of course, while I know there is more work to be done, I again think this time will be different.
There has been a lot of excessive confirmation bias here over the years, admittedly including myself. I have been a strong believer since my initial Geron awareness and a very strong believer since Dr. T’s CT efforts at Mayo. I could only guess of course, but I believe the road is littered with FDA (and associated corporate sponsors) shenanigans, both large and small in that time. I don’t think anyone involved in this space over the last decade plus could or would deny the probability of what IMHO is undeniable. And that is after subtracting out possibility of Geron mistakes, execution and judgement failures.
Rationale for FDA administering delays and restricting designations and accelerators might have had some minor justification at times although even then they must cruelly face down most patients who are in their 70’s and have no other options of merit. However, the other side of that coin has the obvious, much more likely intentions, which have real costs to the Geron strategies, as well as investors and obviously patients, tens of thousands that are no longer with us including many family members, friends and fellow board members. Secondary impacts like blood supply, its quality, caregiver time and costs, next tier advancements, etc. have major untold costs. And of course, delays benefit competitors and their investors via stock portfolios, revenue streams and drug pipelines as well as leverage on partnership and B/O costs and the funds to use for M&A on Geron or other pharma’s, etc.
Anyway, for all the reasons that have been mentioned now and over the years, Geron and Imetelstat IMO are finally on the cusp of greatness. Most, maybe all of us, cannot fully comprehend the potential of Imetelstat and associated IP along with combinations and future related research discoveries like malignant cell death being invoked by ferroptosis. However, each successive time we make it to the alter, I believe we have improved likelihood of approval with revenue and relief just around the corner for MDS and MF patients as well as those with other heme malignancies.
Investors are likely due for success as well this time around. And as Charlie Munger would say, most of us only get a couple opportunities in our lifetimes accumulate generational wealth. I personally think this may be one of those times. Yet I know, the possibility is there for further delays and disappointments and the last time our confirmation bias was this high was September 2018 and that didn’t end well. Of course, while I know there is more work to be done, I again think this time will be different.
Re: FDA v. Geron
Imetelstat is a breakthrough blood cancer medicine that works for many today, and has almost unlimited potential (kills cancer stem-cells in two ways) in combinations going forward. The 12 YES, 2 NO votes was 100% favored by the ODAC oncology hematologists.
“ While a significant minority of patients clearly benefited from imetelstat, a majority of patients do not derive benefit. " -Ravi Madan ODAC Chair
Note: Imetelstat is a life changing medicine for this significant minority, and meets the necessary safety requirements. Benefits include transfusion independence, feeling better, survival time increases, quality of life improvements and disease modification. This is the tip of the iceberg for the Cancer Moonshot (NIH), and an important building block for developing new treatments and cures for all cancers.
“ While a significant minority of patients clearly benefited from imetelstat, a majority of patients do not derive benefit. " -Ravi Madan ODAC Chair
Note: Imetelstat is a life changing medicine for this significant minority, and meets the necessary safety requirements. Benefits include transfusion independence, feeling better, survival time increases, quality of life improvements and disease modification. This is the tip of the iceberg for the Cancer Moonshot (NIH), and an important building block for developing new treatments and cures for all cancers.
-
biopearl123
- Posts: 1676
- Joined: Fri Jul 20, 2018 5:13 pm
Re: FDA v. Geron
Ravi, Ravi, Ravi, of course they do. HI is broken out into major (Complete TI) and minor (Partial TI) the latter is described as a 50% reduction in TR over 16 weeks (but not complete TI, still impressive). These two groups compose is a majority of patients in the study (about 70 total), of course they benefit. Even if they didn’t make TI what about their substantial hemoglobin rises? To repeat Hgb up >3.5 that’s substantial. Ravi, I am perplexed. Did you mean what you said because if you did you might want to reconsider.
Re: FDA v. Geron
The Chair (Ravi) was not up to speed on the importance of Imetelstat to the blood cancer world as a vital 'tool' in transfusion control and well beyond (quality of life, increased survival time, disease modification, combinations, hemoglobin increases ). I suspect he is there by now.
=======================
=======================
From March 27 (LWS)
As far as the two no votes, I believe the Chair (solid cancer oncologist) thought too many non-responsers had to go through the initial disease ( cytopenias -- that could be controlled), and there was no benefit to them. I cannot explain the other no vote (the statistician). The Chairperson was a bit out of his field of expertise (IMO).
Re: FDA v. Geron
In the case of ODAC (Oncology Drug Advisory Committee) when they recommend positively and overwhelmingly (12 Yes to 2) the FDA has NEVER rejected their expert advise. I know of no blood cancer oncologist that has spoken against RYTELO (Imetelstat). Many have spoken publicly on its behalf.
Oncology Drug Advisory Committee Recommendations and the US Food and Drug Administration’s Actions
Alyson Haslam, PhD
Jennifer Gill, MS
Vinay Prasad, MD, MPH
Mayo Clinic Proceedings
From: LETTER TO THE EDITOR| VOLUME 95, ISSUE 2, P424-426, FEBRUARY 2020NOTE: Of the 61 ODAC decisions, 30 were in favor of approval (all FDA approved), 30 were against (7 approved), and there was 1 tie (FDA approved).
Oncology Drug Advisory Committee Recommendations and the US Food and Drug Administration’s Actions
Alyson Haslam, PhD
Jennifer Gill, MS
Vinay Prasad, MD, MPH
Mayo Clinic Proceedings
-
huntingonthebluffs
- Posts: 253
- Joined: Wed Feb 24, 2016 12:00 am
Re: FDA v. Geron
I have a couple questions I would appreciate if maybe some members here could help shed some light on. While I believe the FDA was throwing out misleading statements (maybe flagrantly) while manipulating statistics to support their obvious air balls, a couple points might have some bearing but hopefully minor at best. Maybe my paranoia is just getting the best of me.
1. Is it a real concern regarding the limited number of patients in the P3 located in the US vs Europe? It seems to me that the P2 was weighted to the US and should have helped on that count. The US and European populations are not dissimilar. Also it seems the weighting in the EU for the P3 may have been by design as the EU has the MAA before them as well. Still, it seems that more patients located in the US would have been appropriate. Is this a legitimate concern or just more flak from the FDA?
2. Did the FDA have a valid point regarding the 7.5 mg/kg of intravenous Imetelstat every 4 weeks as the only dosage explored in MDS. The dosage has been in play for 10 years or more, seems to me that for the FDA to bring that up at this juncture is just another false fire alarm. The hematologists and oncologists are skilled at adjusting the dosage or even holding off as needed to allow the cytopenia’s to normalize to acceptable levels. I think the dosage was likely identified in 2014 or maybe 2015 so it wasn’t just pulled out of the hat and Dr. Tefferi probably had considerable input on it. Why did the FDA bring it up now?
TIA
1. Is it a real concern regarding the limited number of patients in the P3 located in the US vs Europe? It seems to me that the P2 was weighted to the US and should have helped on that count. The US and European populations are not dissimilar. Also it seems the weighting in the EU for the P3 may have been by design as the EU has the MAA before them as well. Still, it seems that more patients located in the US would have been appropriate. Is this a legitimate concern or just more flak from the FDA?
2. Did the FDA have a valid point regarding the 7.5 mg/kg of intravenous Imetelstat every 4 weeks as the only dosage explored in MDS. The dosage has been in play for 10 years or more, seems to me that for the FDA to bring that up at this juncture is just another false fire alarm. The hematologists and oncologists are skilled at adjusting the dosage or even holding off as needed to allow the cytopenia’s to normalize to acceptable levels. I think the dosage was likely identified in 2014 or maybe 2015 so it wasn’t just pulled out of the hat and Dr. Tefferi probably had considerable input on it. Why did the FDA bring it up now?
TIA
-
Hoosier Investor
- Posts: 134
- Joined: Thu Jun 18, 2020 5:48 pm
Re: FDA v. Geron
My take on your questions.....
#1) I don't believe the number of US based patients in the P3 should be an issue. First, I'm not aware of a minimum number of required US patients being stipulated (upfront) in the P3 trial design. Second, I don't believe they have any reason to question the validity (or applicability) of the non-US patients in the trial. Third, the two patients who spoke as part of the ODAC (Spkr #3 and Spkr #9) were both US based patients.....both were administered the drug via the Extended Access Program (EAP) after the P3 based on their stated dates of trial enrollment.
#2) I don't believe this should be a concern either. First, this was a P3 trial....not a P2 trial. Phase 2 trials are where you're supposed to determine the optimal dose / dosage protocol. Geron completed their P2 trial, and they were allowed to proceed to P3 trial. P3 is where/when you're confirming statistical efficacy with acceptable safety. Second, if they FDA thinks it through, they'll realize the initial dose is most likely going to deviated from (most cases) after only a few treatments. This is what Geron has said the Heme doctors are very good at (i.e. dose modifications as a means to manage the early cytopenias that are associated with the drug's MOA). Thus, it's not like the recommended dose is going to be set in stone in a fixed (can't be adjusted) manner.
Interestingly, at least one of the patients (#3) who spoke in the ODAC had tried luspatercept prior to imetelstat. The FDA is likely going to be more concerned about the breadth of the label given the small number of P3 patients who were R/R to luspatercept. I can't recall if patient #9 had been on luspatercept (prior to imetelstat) treatment or not.
I suspect the FDAs biggest debate is whether to restrict the label to post-ESA treatment only, or to allow the label to include post-ESA and post-luspatercept treated patients (i.e R/R to ESA only, or R/R to either ESA or Luspatercept).
I was happy to hear Dr. Scarlett mention they've had more conversations with FDA following the ODAC event, and they've provided their input/recommendations on the appropriate label to the FDA. These comments taken together with Geron's continued hiring gives me comfort that we're likely to gain FDA approval for LR-MDS.
#1) I don't believe the number of US based patients in the P3 should be an issue. First, I'm not aware of a minimum number of required US patients being stipulated (upfront) in the P3 trial design. Second, I don't believe they have any reason to question the validity (or applicability) of the non-US patients in the trial. Third, the two patients who spoke as part of the ODAC (Spkr #3 and Spkr #9) were both US based patients.....both were administered the drug via the Extended Access Program (EAP) after the P3 based on their stated dates of trial enrollment.
#2) I don't believe this should be a concern either. First, this was a P3 trial....not a P2 trial. Phase 2 trials are where you're supposed to determine the optimal dose / dosage protocol. Geron completed their P2 trial, and they were allowed to proceed to P3 trial. P3 is where/when you're confirming statistical efficacy with acceptable safety. Second, if they FDA thinks it through, they'll realize the initial dose is most likely going to deviated from (most cases) after only a few treatments. This is what Geron has said the Heme doctors are very good at (i.e. dose modifications as a means to manage the early cytopenias that are associated with the drug's MOA). Thus, it's not like the recommended dose is going to be set in stone in a fixed (can't be adjusted) manner.
Interestingly, at least one of the patients (#3) who spoke in the ODAC had tried luspatercept prior to imetelstat. The FDA is likely going to be more concerned about the breadth of the label given the small number of P3 patients who were R/R to luspatercept. I can't recall if patient #9 had been on luspatercept (prior to imetelstat) treatment or not.
I suspect the FDAs biggest debate is whether to restrict the label to post-ESA treatment only, or to allow the label to include post-ESA and post-luspatercept treated patients (i.e R/R to ESA only, or R/R to either ESA or Luspatercept).
I was happy to hear Dr. Scarlett mention they've had more conversations with FDA following the ODAC event, and they've provided their input/recommendations on the appropriate label to the FDA. These comments taken together with Geron's continued hiring gives me comfort that we're likely to gain FDA approval for LR-MDS.
-
huntingonthebluffs
- Posts: 253
- Joined: Wed Feb 24, 2016 12:00 am
Re: FDA v. Geron
Thanks Hoosier Investor for your detailed and thoughtful reply. I appreciate your understanding of the process going on between the FDA and Geron as well as your confidence in and interpretation of the tea leaves leading to likely approval for Imetelstat. Very helpful to me and I suspect other board members and readers.
Regarding your perceptive point that the labeling allowing Imetelstat for treatment for patients R/R to luspatercept, based on what little I know and mostly via Google, would you agree that it reasonable to include luspatercept R/R patients since luspatercept’s MOA is that it addresses anemia through the improvement of late‐stage erythropoiesis (i.e. red blood cell production), whereas ESAs act only on early‐stage erythropoiesis. So at least both are focused on treating anemia through stimulating red blood cell production, while they differ in the early vs late stage development of the blood cells. In fact, both ESAs and luspatercept have apparently been used in combination at leaset in initial exploratory combination treatment as noted in a research letter dated 7/17/23: “Luspatercept neutralizes TGF-B ligands which negatively regulates terminal erythroid maturation.5 ESA promote early stages of erythropoiesis, whereas, luspatercept enhances terminal erythroid maturation; thus, the combination of ESA and luspatercept may have synergistic effect, which provides the study rationale of evaluating the response rate for this combination.6 Notably, there are overall minimal adverse events in MDS patients with either therapy and no concern of overlapping toxicities.” Obviously both being focused on anemia doesn’t make the case but certainly contributes to the decision.
Assuming that luspatercept is now available for treatment for RS +/-. I would hope that especially in those patients being RS negative and R/R to luspatercept would not be prevented from using Imetelstat. Is that the major issue here with your point, as that is Imetelstat’s primary focus and represents the largest share of the LR MDS population? Thanks again for your assessments.
Regarding your perceptive point that the labeling allowing Imetelstat for treatment for patients R/R to luspatercept, based on what little I know and mostly via Google, would you agree that it reasonable to include luspatercept R/R patients since luspatercept’s MOA is that it addresses anemia through the improvement of late‐stage erythropoiesis (i.e. red blood cell production), whereas ESAs act only on early‐stage erythropoiesis. So at least both are focused on treating anemia through stimulating red blood cell production, while they differ in the early vs late stage development of the blood cells. In fact, both ESAs and luspatercept have apparently been used in combination at leaset in initial exploratory combination treatment as noted in a research letter dated 7/17/23: “Luspatercept neutralizes TGF-B ligands which negatively regulates terminal erythroid maturation.5 ESA promote early stages of erythropoiesis, whereas, luspatercept enhances terminal erythroid maturation; thus, the combination of ESA and luspatercept may have synergistic effect, which provides the study rationale of evaluating the response rate for this combination.6 Notably, there are overall minimal adverse events in MDS patients with either therapy and no concern of overlapping toxicities.” Obviously both being focused on anemia doesn’t make the case but certainly contributes to the decision.
Assuming that luspatercept is now available for treatment for RS +/-. I would hope that especially in those patients being RS negative and R/R to luspatercept would not be prevented from using Imetelstat. Is that the major issue here with your point, as that is Imetelstat’s primary focus and represents the largest share of the LR MDS population? Thanks again for your assessments.
-
Hoosier Investor
- Posts: 134
- Joined: Thu Jun 18, 2020 5:48 pm
Re: FDA v. Geron
Huntington,
I expect our label will be restricted to LR-MDS patients who are R/R to ESAs. This was the original target & goal of the trial, and the trial was designed accordingly. As has been previously communicated, the trial met its primary & secondary objectives in what appears to be an acceptable manner. On top of that, we have a 12-2 ODAC vote in favor of approval. Therefore, it seems highly likely we'll gain FDA approval in this LR-MDS indication.
I don't expect the label to also include LR-MDS patients who are R/R Luspatercept. This is because of the low number of patients in the trial who were R/R Luspatercept. CKTC pointed out a while back that the trial only had six (6) patients meeting who had been treated with Luspatercept. Patients #3 and #9 who spoke in the ODAC had both tried & failed Luspatercept before realizing outstanding results on Imetelstat. Thus, we have at least eight (8) data points on Imetelstat in patients who were also treated with Luspatercept.....with at least two very good outcomes. However, given the need for statistical significance (as measured by p-values), a subgroup within the trial with N=8 patients is likely going to fall short of the FDA's evidence requirement. If we don't gain approval in this indication, Geron may want/need to run a follow-up study in that LR-MDS patient population.....as first suggested by CKTC a few weeks ago.
I expect our label will be restricted to LR-MDS patients who are R/R to ESAs. This was the original target & goal of the trial, and the trial was designed accordingly. As has been previously communicated, the trial met its primary & secondary objectives in what appears to be an acceptable manner. On top of that, we have a 12-2 ODAC vote in favor of approval. Therefore, it seems highly likely we'll gain FDA approval in this LR-MDS indication.
I don't expect the label to also include LR-MDS patients who are R/R Luspatercept. This is because of the low number of patients in the trial who were R/R Luspatercept. CKTC pointed out a while back that the trial only had six (6) patients meeting who had been treated with Luspatercept. Patients #3 and #9 who spoke in the ODAC had both tried & failed Luspatercept before realizing outstanding results on Imetelstat. Thus, we have at least eight (8) data points on Imetelstat in patients who were also treated with Luspatercept.....with at least two very good outcomes. However, given the need for statistical significance (as measured by p-values), a subgroup within the trial with N=8 patients is likely going to fall short of the FDA's evidence requirement. If we don't gain approval in this indication, Geron may want/need to run a follow-up study in that LR-MDS patient population.....as first suggested by CKTC a few weeks ago.