https://www.thebrackengroup.com/blog/ad ... %20meeting.
I saw someone posted a couple weeks ago we were scheduled for April 2024 (I do not know where they go this and dont believe it has been set)
My feeling is the FDA is comfortable with approval and use for MDS otherwise they would not have granted EAP - why the ADCOM and bringing in people more versed in what how imetelstat works? I think they want to look at the whole enchilada and get opinions of the data to date for not only MDS but for MF and possibly AML (which is supposed to have date by Jan 2024 I believe) - they can't get this Adcom together within the time frame of accelerated approval so it was given standard
ADCOM
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: ADCOM
My feeling is the FDA is comfortable with approval and use for MDS otherwise they would not have granted EAP - why the ADCOM and bringing in people more versed in what how imetelstat works? –from rccola
=========================
I agree with you. The EAP (Extended Access Program) seems to be an informal approval, until the FDA advisory committee (ADCOM) can get everything together. The timeline is flexible.
The FDA advisory committee (open to the public) will use the continuing resource of EAP data (that they established) to address patients' current unmet needs and to get the pending NDA (for Imetelstat) approved in a timely way, hopefully post-haste. I believe that the FDA is onboard with Imetelstat, its successes and its potential.
=========================
Time & Timelines:
The line of evidence: Conferences (ASCO, EHA), KOLs, Webinars, MD Anderson, NDA submitted, EAP, NDA accepted, timeline to NDA approval (continuing question). I see no more obstacles on the medical side. --- from LWS
Re: ADCOM
ADCOM and Dr. Zeidan and others
Thanks rccola for this article. This excerpt puts 'the ball' in the FDA's 'court', especially with patients' unmet needs.
====================
Excerpt from article:
How are these updated findings going to influence the future of this space and research?
The next step will be submitting these findings to the regulatory agencies, the company is already doing this, and this will be reviewed by the FDA. My expectation is that the drug will hopefully get regulatory approval based on the efficacy and safety data, and if that happens, it will be an important option for our patients because while we have other agents that we can use in this space, such as lenalidomide. Generally, those drugs do not lead to responses in all patients. Actually, less than 50% of patients do not respond and their responses are not durable, so most patients need additional options. I think having a drug that's very active, well-tolerated, and potentially can modify the disease's natural course would be an important option to give to our patients.
REFERENCE:
Zeidan AM, Platzbecker U, Santini V, et al. IMerge: Results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). J Clin Oncol. 2023;41(suppl 16):7004. doi:10.1200/JCO.2023.41.16_suppl.7004
Thanks rccola for this article. This excerpt puts 'the ball' in the FDA's 'court', especially with patients' unmet needs.
====================
Excerpt from article:
How are these updated findings going to influence the future of this space and research?
The next step will be submitting these findings to the regulatory agencies, the company is already doing this, and this will be reviewed by the FDA. My expectation is that the drug will hopefully get regulatory approval based on the efficacy and safety data, and if that happens, it will be an important option for our patients because while we have other agents that we can use in this space, such as lenalidomide. Generally, those drugs do not lead to responses in all patients. Actually, less than 50% of patients do not respond and their responses are not durable, so most patients need additional options. I think having a drug that's very active, well-tolerated, and potentially can modify the disease's natural course would be an important option to give to our patients.
REFERENCE:
Zeidan AM, Platzbecker U, Santini V, et al. IMerge: Results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). J Clin Oncol. 2023;41(suppl 16):7004. doi:10.1200/JCO.2023.41.16_suppl.7004
Re: ADCOM
Dr Mikkael Sekeres expressed his disappointment that he would not have this available this year (makes you wonder what thr EAP really does)
Couple years ago I watched a podcast with him and Dr Steensma and it was encouraging to see their plans to use imetelstat in thr treatments - the heme/onc’s seem to want this drug as a treatment option and this has kept me on board with imetelstat
Couple years ago I watched a podcast with him and Dr Steensma and it was encouraging to see their plans to use imetelstat in thr treatments - the heme/onc’s seem to want this drug as a treatment option and this has kept me on board with imetelstat
Re: ADCOM
I believe that the FDA advisory review committee (ADCOM) will put Imetelstat into proper perspective, as a miracle blood cancer medicine (cancer disease modification, kills cancer stem cells, transfusion independence, unmet patients' needs, combination synergies) that is in a class by itself. Since these hearings are apparently open to the public we can listen and learn.
I only hear and read positive comments about Imetelstat (medically) these days. The review articles, conferences, KOLs, the EAP and Webinars all point to NDA approvals soon.
I only hear and read positive comments about Imetelstat (medically) these days. The review articles, conferences, KOLs, the EAP and Webinars all point to NDA approvals soon.
Re: ADCOM
I only hear and read positive comments about Imetelstat (medically) these days. The review articles, conferences, KOLs, the EAP and Webinars all point to NDA approvals soon.--LWS
===================================
The two subjects that I would like to get more information about are:
1/ The EAP (Extended Access Program)
a/ Is this program being used now and where?
b/ Is this an additional source of data for the ADCOM beyond the phase 3 data?
c/ Can this be considered a type of practical & current interim approval?
d/ While we are waiting for final approval, are MDS patients able to get easy-access to Imetelstat?
2/ The ADCOM (FDA Advisory Committee)
a/ When is the initial meeting about the Imetelstat NDA approval?
b/ Will this meeting be open to the public?
c/ Will there be internet access?
d/ How can they affect the timeline?
===================================
The two subjects that I would like to get more information about are:
1/ The EAP (Extended Access Program)
a/ Is this program being used now and where?
b/ Is this an additional source of data for the ADCOM beyond the phase 3 data?
c/ Can this be considered a type of practical & current interim approval?
d/ While we are waiting for final approval, are MDS patients able to get easy-access to Imetelstat?
2/ The ADCOM (FDA Advisory Committee)
a/ When is the initial meeting about the Imetelstat NDA approval?
b/ Will this meeting be open to the public?
c/ Will there be internet access?
d/ How can they affect the timeline?
Re: ADCOM
When the time comes for the ADCOM, KOLs will likely advocate for the drug as will patients and families. All we have have to do is wait. And wait.--- from bp
=========================================================
Unless we are all missing something, the NDA (for Imetelstat) will be approved in a timely manner. I hesitate to use the word miracle, at this point in time, but adjectives such as exceptional, remarkable and durable have been used when describing this medicine. So, it all comes down to when (not if). There are many advocates for Imetelstat (professionals in medicine and science + patients), that will be heard by the ADCOM. Patients' unmet needs always are most important. The timeline is flexible (IMO).
Re: ADCOM - LWS
dont forget the KOL who referred to imetelstat as a "game changer" - do you recall who it was ?
Re: ADCOM
Timeline From the "May Miracle" to ASH: IMerge, EHA, Lancet, ASH2023
Thanks bp for the Lancet/Dr. Platzbecker article (coming). This excerpt should interest the ADCOM and the FDA in general.
====================================================
What other data are relevant in the lower-risk MDS space?
We have another trial, the IMerge trial [NCT02598661]; [findings have] been presented at the European Hematology Association 2023 Hybrid Congress, and is now in press with The Lancet, and the 2023 American Society of Clinical Oncology Annual Meeting.6,7 The trial is a different study [from COMMANDS] because only patients who [had] ESA-relapsed or [ESA]-refractory [disease] were included. It’s an ESA-exposed cohort of patients with lower-risk MDS [and] with a high transfusion burden, meaning that patients had to have at least 4 units of red blood cells within 8 weeks compared with COMMANDS, where the threshold was at least 2 units of red blood cells within 8 weeks. The majority, basically two-thirds of the patients, had the RS phenotype, and the others [had the] non-RS [phenotype]. This trial investigated [patients] in a placebo-controlled way, with a 2:1 randomization to imetelstat, a first-in-class telomerase inhibitor, given every 4 weeks as an infusion as outpatient [care] vs placebo, with the primary end point of 8-week transfusion independence rate.
The study met its primary end point, [with findings] showing a superiority of transfusion independence rate in patients receiving imetelstat, which is very good news as well. There was a 40% response rate vs 15% for the primary end point. But interestingly, a substantial amount of patients, [approximately] 18%, also achieved a 1-year transfusion independence rate. So the durability was meaningful, especially given that many of these patients had a high transfusion burden, and transfusion independence is hardly achieved with currently available conventional therapies in the second line. Also important to note is that quality of life was improved, specifically fatigue.
Last but not least, we need to talk about safety. There were no new signals detected; hematologic toxicity [such as] neutropenia and thrombocytopenia occurred in the majority of the patients but was also reversible in short term in the majority of the patients, so it can be easily managed by an experienced hematologist. The new drug application was also submitted to the FDA [and accepted] on August 21, 2023.8 We don’t know what the future will bring, but it’s expected and hoped that the drug will be approved as a second-line therapy for all eligible patients with lower-risk MDS.
How may these trials affect sequencing therapies in this population?
This will open the avenue for new thinking with regard to sequencing. It depends very much, though, on the approval and the way the drugs will be approved in North America but also in the European Union. Luspatercept may become the new first-line option for a still to be defined large portion of LR-MDS patients. However, imetelstat could be the preferred second-line therapy, especially for patients with a high transfusion burden.
Do you have any advice for community oncologists who treat these patients?
Community oncologists have experience already with luspatercept. It’s an easy and injectable every-3-weeks agent that has a good safety profile. Based on [findings from] the COMMANDS trial, responses occurred in the majority of patients during the first 6 months, so you should not give up after 2 injections—continue and dose escalate.
For imetelstat, it’s an easy to use every-4-week intravenous infusion over 2 hours. It can be nicely done also in the outpatient setting. Cytopenias occur mainly after 2 weeks in these patients but, at least in the clinical trials, were not harmful with regard to a higher mortality rate. But still, especially in the first cycles, I would recommend very close surveillance with regard to these patients, including granulocyte colony-stimulating factor use [and] transfusion support. And depending on the nadir and what happens after the first and second cycle, the dose may be adjusted [or] reduced or the distance between the cycles could be extended. In the early phase, the first 2 cycles, patients need to be watched carefully. But longer term, patients can stay on imetelstat very safely. The neutropenia and thrombocytopenia [can be] mitigated after the first 2 or 3 cycles, so I think that practical perspective [is] quite important. As hematologic oncologists, we give cytotoxic agents to most of our patients, so this is something we can definitely handle.
References
1. Platzbecker U. Update on treatment of lower risk MDS. Presented at: Society of Hematologic Oncology Annual Meeting; September 6-9, 2023; Houston, TX.
Thanks bp for the Lancet/Dr. Platzbecker article (coming). This excerpt should interest the ADCOM and the FDA in general.
====================================================
What other data are relevant in the lower-risk MDS space?
We have another trial, the IMerge trial [NCT02598661]; [findings have] been presented at the European Hematology Association 2023 Hybrid Congress, and is now in press with The Lancet, and the 2023 American Society of Clinical Oncology Annual Meeting.6,7 The trial is a different study [from COMMANDS] because only patients who [had] ESA-relapsed or [ESA]-refractory [disease] were included. It’s an ESA-exposed cohort of patients with lower-risk MDS [and] with a high transfusion burden, meaning that patients had to have at least 4 units of red blood cells within 8 weeks compared with COMMANDS, where the threshold was at least 2 units of red blood cells within 8 weeks. The majority, basically two-thirds of the patients, had the RS phenotype, and the others [had the] non-RS [phenotype]. This trial investigated [patients] in a placebo-controlled way, with a 2:1 randomization to imetelstat, a first-in-class telomerase inhibitor, given every 4 weeks as an infusion as outpatient [care] vs placebo, with the primary end point of 8-week transfusion independence rate.
The study met its primary end point, [with findings] showing a superiority of transfusion independence rate in patients receiving imetelstat, which is very good news as well. There was a 40% response rate vs 15% for the primary end point. But interestingly, a substantial amount of patients, [approximately] 18%, also achieved a 1-year transfusion independence rate. So the durability was meaningful, especially given that many of these patients had a high transfusion burden, and transfusion independence is hardly achieved with currently available conventional therapies in the second line. Also important to note is that quality of life was improved, specifically fatigue.
Last but not least, we need to talk about safety. There were no new signals detected; hematologic toxicity [such as] neutropenia and thrombocytopenia occurred in the majority of the patients but was also reversible in short term in the majority of the patients, so it can be easily managed by an experienced hematologist. The new drug application was also submitted to the FDA [and accepted] on August 21, 2023.8 We don’t know what the future will bring, but it’s expected and hoped that the drug will be approved as a second-line therapy for all eligible patients with lower-risk MDS.
How may these trials affect sequencing therapies in this population?
This will open the avenue for new thinking with regard to sequencing. It depends very much, though, on the approval and the way the drugs will be approved in North America but also in the European Union. Luspatercept may become the new first-line option for a still to be defined large portion of LR-MDS patients. However, imetelstat could be the preferred second-line therapy, especially for patients with a high transfusion burden.
Do you have any advice for community oncologists who treat these patients?
Community oncologists have experience already with luspatercept. It’s an easy and injectable every-3-weeks agent that has a good safety profile. Based on [findings from] the COMMANDS trial, responses occurred in the majority of patients during the first 6 months, so you should not give up after 2 injections—continue and dose escalate.
For imetelstat, it’s an easy to use every-4-week intravenous infusion over 2 hours. It can be nicely done also in the outpatient setting. Cytopenias occur mainly after 2 weeks in these patients but, at least in the clinical trials, were not harmful with regard to a higher mortality rate. But still, especially in the first cycles, I would recommend very close surveillance with regard to these patients, including granulocyte colony-stimulating factor use [and] transfusion support. And depending on the nadir and what happens after the first and second cycle, the dose may be adjusted [or] reduced or the distance between the cycles could be extended. In the early phase, the first 2 cycles, patients need to be watched carefully. But longer term, patients can stay on imetelstat very safely. The neutropenia and thrombocytopenia [can be] mitigated after the first 2 or 3 cycles, so I think that practical perspective [is] quite important. As hematologic oncologists, we give cytotoxic agents to most of our patients, so this is something we can definitely handle.
References
1. Platzbecker U. Update on treatment of lower risk MDS. Presented at: Society of Hematologic Oncology Annual Meeting; September 6-9, 2023; Houston, TX.
Re: ADCOM
The FDA has recently granted one form of approval for Imetelstat (EAP--- Extended Access Program). Any person with MDS qualifies for treatment with Imetelstat, as I understand it. This is obviously an interim solution and a precursor to NDA approval, as the ADCOM hears from the KOLs (Key Opinion Leaders -- the medical and scientific leaders). The timeline is flexible, and, I believe, will be adjusted by overwhelming positive evidence.
Imetelstat is an exceptional, remarkable, and durable platform medicine, that is needed now by a spectrum of blood cancer patients. I believe that the ADCOM exposure will be very favorable for Imetelstat.
Imetelstat is an exceptional, remarkable, and durable platform medicine, that is needed now by a spectrum of blood cancer patients. I believe that the ADCOM exposure will be very favorable for Imetelstat.
Re: ADCOM
LWS: Why do you quote your own post(s) and then copypasta remarks from Dr. Platzbecker and a few common posters on this board? We all have the same access to the same interviews from Platzbecker and the same access to previous posts on imetelchat from BP and kmall and others.
Why do you find it essential to bury the board in copypasta and your subjective reasoning?
Why do you find it essential to bury the board in copypasta and your subjective reasoning?
Re: ADCOM
KT --- Imetelchat is a chatroom. This is my way of chatting with summaries, updates, new findings and what I believe to be conclusive evidence of Imetelstat's value in a variety of blood cancers now (single-agent) and in various combinations going forward.
The false and misleading information about this medicine needs to be identified and exposed for both patients and investors. My belief is that will happen at the forthcoming ADCOM open, public discussions and hearings, with a combination of KOLs (experts) and solid, repeatable data from numerous trials. These ADCOM events are a follow-up to the recently granted EAP.
New people are finding this chatroom and are discovering Imetelstat. I believe having longer and continuous strings allows them to put this medicine into proper perspective as an "exceptional, remarkable and durable" blood cancer medicine.
The false and misleading information about this medicine needs to be identified and exposed for both patients and investors. My belief is that will happen at the forthcoming ADCOM open, public discussions and hearings, with a combination of KOLs (experts) and solid, repeatable data from numerous trials. These ADCOM events are a follow-up to the recently granted EAP.
New people are finding this chatroom and are discovering Imetelstat. I believe having longer and continuous strings allows them to put this medicine into proper perspective as an "exceptional, remarkable and durable" blood cancer medicine.
Re: ADCOM
LWS: Going forward, how much weight does your "conclusive evidence" hold for imetelstat's CT data with the FDA and the upcoming advisory panel hearing?
Will your "conclusive evidence" be used to inform the advisory committee in the coming months? Because I'm pretty sure that Geron already has your copypasta covered.
Will your "conclusive evidence" be used to inform the advisory committee in the coming months? Because I'm pretty sure that Geron already has your copypasta covered.
Re: ADCOM
From KT: Will your "conclusive evidence" be used to inform the advisory committee in the coming months?
=================================================================
Obviously, it is an overwhelming combination of “conclusive evidence”:
1/ The successful phase 3 trials
2/ The conferences (EHA, ASCO leading to ASH2023)
3/ The experts (KOLs, Webinars, MD Anderson, etc.)
4/ Transfusion independence, survival time, safety, uniqueness, fatigue factor
5/ Fast track, orphan drug status, EAP
6/ Disease modification, kills cancer stem cells
7/ Combination potential and synergies
8/ Patients’ immediate and unmet needs
9/ The medical journals (Lancet and others)
10/ NDA submitted, accepted and near approval (timeline flexible)
The ADCOM and the FDA will not ignore the obvious.
=================================================================
Obviously, it is an overwhelming combination of “conclusive evidence”:
1/ The successful phase 3 trials
2/ The conferences (EHA, ASCO leading to ASH2023)
3/ The experts (KOLs, Webinars, MD Anderson, etc.)
4/ Transfusion independence, survival time, safety, uniqueness, fatigue factor
5/ Fast track, orphan drug status, EAP
6/ Disease modification, kills cancer stem cells
7/ Combination potential and synergies
8/ Patients’ immediate and unmet needs
9/ The medical journals (Lancet and others)
10/ NDA submitted, accepted and near approval (timeline flexible)
The ADCOM and the FDA will not ignore the obvious.
Re: ADCOM
"The ADCOM and the FDA will not ignore the obvious."
Subjective reasoning.
Government agencies regularly ignore the obvious.
Shall I create a list of multiple government agencies that regularly "ignore the obvious," or are you content with your ultracrepidarian, copypasta posts?
Subjective reasoning.
Government agencies regularly ignore the obvious.
Shall I create a list of multiple government agencies that regularly "ignore the obvious," or are you content with your ultracrepidarian, copypasta posts?
Re: ADCOM
"The ADCOM and the FDA will not ignore the obvious." --- from LWS
"Government agencies regularly ignore the obvious." ---- from KT
I have complete confidence that both the ADCOM and the full FDA will be objective in their decisions concerning Imetelstat. The evidence appears to be "compelling", complete and positive in the 10 items that I listed.
==================================================================
This is a new word for me.
ul·tra·crep·i·dar·i·an
ADJECTIVE
1. expressing opinions on matters outside the scope of one's knowledge or expertise:
“Dad, how do we know the universe is expanding?” inquires your six-year-old. Try answering that without resorting to an ultracrepidarian trick here or there"
NOUN
1. a person who expresses opinions on matters outside the scope of their knowledge or expertise:
"most patients are ultracrepidarians when it comes to medicine"
"Government agencies regularly ignore the obvious." ---- from KT
I have complete confidence that both the ADCOM and the full FDA will be objective in their decisions concerning Imetelstat. The evidence appears to be "compelling", complete and positive in the 10 items that I listed.
==================================================================
This is a new word for me.
ul·tra·crep·i·dar·i·an
ADJECTIVE
1. expressing opinions on matters outside the scope of one's knowledge or expertise:
“Dad, how do we know the universe is expanding?” inquires your six-year-old. Try answering that without resorting to an ultracrepidarian trick here or there"
NOUN
1. a person who expresses opinions on matters outside the scope of their knowledge or expertise:
"most patients are ultracrepidarians when it comes to medicine"
Re: ADCOM
I think we all are frustrated and edgy - this should not be taking until June of 2024 for MDS approval - KOL’s are excited about imetelstat’s potential and were anticipating it’s availability before the end of the year
We have not gotten the date for the ADCOM - I expect it requires a lot of scheduling to get everyone on board
We are due a positive press release otherwise the stock will be a punching bag until next June
We have not gotten the date for the ADCOM - I expect it requires a lot of scheduling to get everyone on board
We are due a positive press release otherwise the stock will be a punching bag until next June
Re: ADCOM
from rccola --- KOL’s are excited about imetelstat’s potential and were anticipating it’s availability before the end of the year.
===============================
The experts are the KOLs (Key Opinion Leaders) that have the experience, education, and medical background to judge Imetelstat properly. My opinion, based upon the available evidence that has been published and the EAP, is that Imetelstat is already an accepted medicine by most (if not all) of the KOLs, and is only waiting for the ADCOM to get organized for detailed public hearings. The EAP, as I understand it, allows anyone with MDS access to Imetelstat (today) before final NDA approval by the FDA (dotting the (i's) & crossing the (t's)).
The timeline has been way too long, and hopefully the ADCOM will be able to significantly shorten it.
Imetelstat is effective, safe and is needed now. Everything is on track and pointing in the right direction (KOLs, EAP, NDA accepted, ADCOM public hearings now in focus).
Disease modification, kills cancer stem cells, fatigue improvement, transfusion independence, longer survival time --- that is what the ADCOM will hear from the KOLs.
===============================
The experts are the KOLs (Key Opinion Leaders) that have the experience, education, and medical background to judge Imetelstat properly. My opinion, based upon the available evidence that has been published and the EAP, is that Imetelstat is already an accepted medicine by most (if not all) of the KOLs, and is only waiting for the ADCOM to get organized for detailed public hearings. The EAP, as I understand it, allows anyone with MDS access to Imetelstat (today) before final NDA approval by the FDA (dotting the (i's) & crossing the (t's)).
The timeline has been way too long, and hopefully the ADCOM will be able to significantly shorten it.
Imetelstat is effective, safe and is needed now. Everything is on track and pointing in the right direction (KOLs, EAP, NDA accepted, ADCOM public hearings now in focus).
Disease modification, kills cancer stem cells, fatigue improvement, transfusion independence, longer survival time --- that is what the ADCOM will hear from the KOLs.
Re: ADCOM
`````````````````````````````
Imetelstat is effective, safe and is needed now. Everything is on track and pointing in the right direction (KOLs, EAP, NDA accepted, ADCOM public hearings now in focus).
Disease modification, kills cancer stem cells, fatigue improvement, transfusion independence, longer survival time --- that is what the ADCOM will hear from the KOLs.
The science and phase 3 trial results will be more than sufficient to get Imetelstat approved. The investment community (dark-side) seems to be focusing on Geron ($1.77), while Goldman Sachs’ has a buy recommendation ($4.00). ADCOM, with public hearings, will put Imetelstat into proper perspective (successes, need, potential).
Additional Thoughts: The future of Imetelstat (obviously) is totally in the hands of the ADCOM (advisory committee to the FDA) and the information they receive from the KOLs (Key Opinion Leaders), the experts in the field of hematology and various forms of blood cancers. The pace of progress to this point has been painfully slow, and the collapse in the PPS has been discouraging. The science and the medical successes are now well documented as being very positive, so there should be no problem for approval of the NDA, hopefully on an accelerated timeline.
"All is well that ends well".