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Italy rejecting again would be bad because it doesn't bode well for France/Germany, which are supposedly more even more difficult to get positive reimbursement.
I'm hoping positive Italy news is the beginning of the stock comeback.
I still don't know what to make of the sdLDL-c analysis. Earlier at ACC, Bhatt presented an analysis of results bucketed by baseline LDL-c less than/greater than 55mg/dl threshold.
The primary outcome rate among patients with LDL-C <55 mg/dL was 16.2% in the IPE group and 22.8% in the placebo group, HR 0.66 (95% CI 0.50-0.87; P=0.003). Findings were consistent in the LDL-C ≥55 mg/dL subgroup, with rates of 17.4% in the IPE group and 21.9% in the placebo group, HR 0.76 (95% CI 0.69-0.85; P<0.0001).
https://amarincorp.com/news-and-media/new-reduce-itr-analyses-show-vasceparvazkepar-icosapent-ethyl
There was efficacy in both subgroups and no statistically significant difference, but the efficacy in the lower LDL-c group was 34% RRR while "only" 24% RRR in the higher LDL-c group. (So there's a hint of a stronger efficacy if anything when LDL-c is better controlled, which helps counter the German argument against us).
This sdLDL-c study presented at ESC on the other hand found an efficacy of 42% RRR in the high sdLDL-c group but only 23%RRR in the lower sdLDL-c group. What's more, the higher sdLDL group only had a total N of 459 vs 7698 for the lower sdLDL-c group. A couple hard facts/ immediate observations: 23%RRR is still very good compared other lipid therapies, and technically there was no significant difference between the higher/lower baseline sdLDL c groups.
But more exploratory, it does seem the efficacy is particularly loaded into the higher baseline sdLDLc group. Maybe a good initial compromise in Germany would be to reimburse based on this sdLDL-c threshold.
Thank you! I see it now. Yes hopefully vazkepa will be included in the discussion. Italy reimbursement is probably the only important event for the remainder of the year.
This was for 2022 no?
Riunione Comitato Prezzi e Rimborso (CPR)
Riunione Comitato Prezzi e Rimborso (CPR) del 21-22-23 settembre 2022.
In any case, we should be getting on one of the next reimbursement meetings with a decision by year end.
Thanks for posting, was this announced recently? Been searching the AIFA website for vazkepa but haven't seen anything since meeting in July.
Good to see you posting Pdude, informative as always. Doldrums for now until hopefully the Italy reimbursement decision later this year.
Amarin's least speculative value is locked in the major EU countries and their reimbursement decisions. Unfortunately there's not much to see until Italy and France decides on reimbursement. We should see Italy's decision within this quarter or perhaps a little after, and France's decision first half of next year. If Italy says no again, that would really worry me.
Not seeing anything as far as I can search. I'll do a deeper look on the AIFA website later today.
Posted last week by @evila on ST. Vazkepa reimbursement discussions by AIFA (Italy) week of July8th through 12th.
https://www.aifa.gov.it/documents/20142/2468753/ODG_CSE_del_8-9-10-11-12_luglio_2024_HTA.pdf
Sorry if this was already posted, I don't recall seeing this on Ihub.
good researching! appreciate it
Posted on ST. More RWE for EPA: https://pubmed.ncbi.nlm.nih.gov/38879457/
"Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log-rank P=0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log-rank P=0.021)."
Small N (673 patients), but was a 5 year followup (retrospective study, like the recent VA study).
Setting aside the obvious motive to knock down the price of Vazkepa, and doing my best to follow the G-BA's logic:
They claim that IPE's efficacy is unproven for patients who have lowered their LDL-c to 55mg/dL (Reduce-IT's median LDL-C before and after was roughly 70mg/dL IIRC). If this claim is true, IPE's benefit would not "stack" with ezetimibe, and the two compete. This still leaves a problem for the German argument, because IPE confers 25%RRR vs ezetimibe's 6% RRR. This is the part where they throw in the mineral oil uncertainty to further "level the playing field" between the two agents.
Anyways, regarding the LDL-c arguments, I believe at the time of submission and discussion, there wasn't an official < 55mg/dL subgroup analysis. Looking at the NEJM article for Reduce-IT, I see this tertile breakdown, where the lowest tertile is <67 mg/dL. The trend strongly suggests <55mg/dL wouldn't make a difference, but that info hasn't been analyzed and published.
That's why Bhatt's presentation in April is so important, it directly challenges the G-BA's point, to the digit. As for the mineral oil arguments, we've accumulated more evidence since (RESPECT, Bhatt's mediation analysis at ESC 2023, in vitro studies by Mason comparing corn oil/MO/epa/dha). I'd love to see something become of the real world data done by the VA hospital researchers, and obviously you and I both want to see MITIGATE.
I'm with you that UK/EU is what will drive the valuation for the eventual BO. Italy/France/Germany and then sold.
Good discussion. One of Germany's criticism was that LDL levels should have been more aggressively lowered in Reduce-IT (ideally <55mg/dL for very high risk to match European guidelines).
I believe Amarin asked Bhatt to help further address that criticism, hence this presentation earlier at ACC 2024 back in April:
https://www.biospace.com/article/releases/new-reduce-it-analyses-show-vascepa-vazkepa-icosapent-ethyl-benefit-in-high-risk-cardiovascular-disease-patient-subgroups/
"Among statin-treated REDUCE-IT patients with baseline LDL-C data, 1,058 (12.9%) had LDL-C <55 mg/dL and 7,117 (87.1 %) had LDL-C ≥55 mg/dL. The primary outcome rate among patients with LDL-C <55 mg/dL was 16.2% in the IPE group and 22.8% in the placebo group, HR 0.66 (95% CI 0.50-0.87; P=0.003). Findings were consistent in the LDL-C ≥55 mg/dL subgroup, with rates of 17.4% in the IPE group and 21.9% in the placebo group, HR 0.76 (95% CI 0.69-0.85; P<0.0001). No significant interaction by baseline LDL-C was observed."
We all already intuitively understand that V has no true comparator, because it's not an LDL-C therapy, and only has a marginal impact on LDL-C (about -5% reduction in ANCHOR). The reduce-it analysis shows that further lowering LDL-C does not make V's benefit wane (if anything, it's slightly more pronounced).
ESC 2024 Late Breaker submissions closed last Thursday.
Call for Late-Breaking Science is now closed
We thank all the Submitters for their contribution.
The results will be announced late June, each submitter will be notified by email.
https://www.escardio.org/Congresses-Events/ESC-Congress/Call-for-Science/Late-Breaking-Science
A congress in London, seems opportune for Amarin to stack this event best they can to help with UK scripts, as well as the rest of EU reimbursement.
I think the reversal of dismissal is pretty much a sure shot. (we got the dream team in Moore, Albright, Lourie and they clearly thought dismissal was premature.) The big question is what happens when it lands back on Judge Andrew's docket. We'd have to survive summary judgement before we get to a jury trial.
Just an FYI regarding the P-value, the VA study had a P value < .05, it's implied by the 95% confidence intervals. (95% CI .56 - .69) They should be able to easily produce the P value if in the actual publication.
Regarding Kaiser, one more real world data set in the form of MITIGATE and that should be all the additional evidence we need for Germany/France.
Kiwi, the details will be presented tomorrow April 8th. I'll try to see if I can find out more tomorrow. The next steps would be to get the study pear reviewed and published before it can be given more weight in the discussions in the EU.
Regarding reduce-it, I was speaking only from memory, so forgive me if it's not exactly a match with this study. But here's a slide showing the total events separation in Reduce-IT. As you can see, total events separated very early (well within the 1st year).
38% reduction in 9.4 months is quite amazing, but probably quite in line with Reduce-IT results if you look at the high risk subgroups and use Total Event Analysis.
If MITIGATE produces similar results, I think we can be done here with the Real world evidence. At some point, we no longer need a confirmation of a confirmation. (these RWE studies already being the confirmation of Reduce-IT, which is already amply supported by Jelis/Respect).
JRoon, I still think there's a chance. In my view, it's not over yet until I see something posted on clinical trials.gov. The VA retrospective study was only for 9.4 months, 2144 patients in each arm (IPE vs Lovaza i'm assuming), and we see a 38% RRR in mace. MITIGATE would be 1500 vs a much bigger control group, and the mean followup should be closer to 12 months or longer.
RWE of Icosapent Ethyl at ACC 2024. 38% MACE relative risk reduction IPE vs OM3. The authors are not even Amarin affiliated, so a truly independent study.
With Bhatt's vascular progenitor study, the new science continues to build in favor of IPE. ESC 2024 will be in London this year end of August. If we get more RWE in the form of MITIGATE, that should make a big difference for the remaining EU reimbursements. Happy to hear Amarin finally PR their European patent wins and exclusivity strength.
JRoon, the same researchers had presented at ACCP last year (this was the RWE study of IPE vs OM3 on just Afib/major bleeding). They are now presenting again at ACC 2024 in April, but this time on RWE for IPE vs OM3 efficacy in MACE.
https://www.abstractsonline.com/pp8/#!/10973/session/1196
I don't have much to go off of here. This is from their part 1 study: "Overall mean follow up time was ~6 months."
https://www.accp.com/meetings/am23/posters.aspx?aid=62711
Their abstract for ACC 2024 is embargoed, so we don't know what follow-up duration they used for part 2. Anyways, I'm not expecting anything eye-popping from these researchers, and I hope they don't have an angle here (the omega-3 index, dietary supplemental cabal out there, trying to "prove" mixed O3 is as good as IPE).
Dar, yes I pulled this from the ACC 2024 schedule planner (April 2024).
The RWE abstract is interesting but the results are not likely to be a homerun IMO. It's the only abstract with researchers not affiliated with Amarin, and they are comparing IPE to an active comparator (Lovaza?) rather than IPE vs no-IPE. We also won't know the duration of observation, but looking at their Part 1 study (for safety findings), the median observation was only 6 months, way too short for efficacy findings. Hope I'm wrong though, and the data proves useful .
I would much rather prefer Amarin/Kaiser also present their MITGATE CVD data, which was at least still a randomized controlled trial, with ~15 month minimum followup.
Anyways, overall not a bad showing for the IPE gang at the first major congress of the year. Glad to finally see IPE-Prevention finally being presented.
Seems like the abstract being presented at ACC is a part 2 followup to something they presented before (they compared incidence of AF/bleeding, IPE vs mixed OM3):
https://www.accp.com/meetings/am23/posters.aspx?aid=62711
The one they will present at ACC will be efficacy on MACE.
Hope you're able to get back on Brand Vascepa. In the meantime, let us know if you feel/notice any differences taking the generic.
Thanks for keeping up with this Kiwi. I'm sure there is RWE for Vascepa, but I'm guessing cleaning/normalizing the messiness of real world data is not a trivial process. The best hope of hearing anything with respect to RWE is Mitigate. Let's keep our fingers crossed for an ACC 2024 presentation. I'm monitoring the programming and will post when it updates.
JR, Kiwi, we might see MITIGATE as a late breaker at ACC 2024 (so around end of this month is when the programming would be announced).
Jasb, yes the bottom line is that it's all about slowing the rate of cognitive decline, ideally to a rate matching those without Alzeimers disease. That is the endgame.
But when we're talking about screening for therapies that could potentially achieve the above, especially in short duration trial, you have to be open to the possibility that drugs that improve outcomes in the near term (whether that's scores on cognitive tests or cerebral blood flow) will be good candidates to achieve the ultimate goal stated above.
Here was the result from a recent clinical trial involving EPA rich oil vs DHA rich oil (and vs Olive Oil). We actually see an improvement in cognition over 6 months. The hope is that signal translates into slowing cognitive decline in the long run.
If BRAVE was supposed to succeed based solely on slowing the rate of decline, then it was badly underpowered (both duration and sample size).
Looks like Sleven/Pdude had correct info. It's a bummer. Hopefully there might still be some hints in the fully analyzed data. For my part, I'm curious if the cohort studied was too healthy and there was a lack of meaningful clinical progression. Of course, I was really hoping the IPE arm would show improvements from baseline, so that a positive readout wouldn't rely on the placebo arm getting much worse.
Here's a look at PACC scores for pre-clinical patients (so a similar risk cohort to Brave) in the failed A4 study. Brave would only be at the 78 week mark, to give a sense comparison.
I believe most of the recent headline making Alz trails these past years have been in patients with mild cognitive decline, and "success" is measured by how much they slow that decline, rather than actual improvements to cognition.
Kiwi, no worries, I enjoy a good conspiracy theory. If you remember Amarin's email to Raf a few months ago regarding MITGATE, they make it pretty clear they don't run the trial.
In general, IIT's may receive funding and drug product from a pharmaceutical company, but all trial data, protocol, and publishing rights usually resides with the PI's institution (usually a university or a research clinic).
"As an Investigator, if your IIT proposal is accepted, Novartis may provide you with financial support and/ or Novartis product(s). However, you will retain full responsibility and control of the design, initiation, management, data analysis, monitoring, and reporting, as the sponsor of the study."
...
As part of Novartis’ commitment to publishing
research, you are encouraged to publish the results of
IITs. As the Investigator, the content of any publication
is your responsibility, and Novartis will not be involved
in authorship selection or writing and should not be
included as a co-author of IIT publications.
https://www.novartis.com/sites/novartis_com/files/novartis-investigator-initiated-trials-guide-prospective-investigators.pdf
This is very standard as far as IIT's go.
Kiwi, Amarin is a collaborator, but they are very clearly not the sponsor, Kaiser is. Here's a side by side of MITIGATE vs Reduce IT on clinical trials.gov. Kaiser/Ambrosy get to call all the shots here in terms of presentation/publishing timeline, venue, or even to do it at all. Of course, Dr. Ambrosy would prefer to present/get published for his own reputation, but Amarin can't force him do anything, especially to make study results disappear, which he is obligated to submit to clinical trial.gov eventually.
Kiwi, JRoon71, the total mystery of what happened to MITIGATE frustrates me as well as I agree there must be some useful data from 1500+ ASCVD patients taking Vascepa over the course of 15 months+.
Kiwi, I don't think Amarin would have any legal authority to silence Ambrosy/Kaiser. They supply the study drug and perhaps some limited funding, but they are not the trial sponsor. If you recall the biomarkers study last year that gave everyone a scare, Amarin didn't have any power to prevent Ridker from publishing the results.
I don't think MITIGATE results can be buried without violating FDA regulations and ethical principles in general. Perhaps we'll finally see the trial results at ACC 2024.
Pdude, here's a link to the Agenda for the March 2024 Alzheimer's conference:
https://alz.org/media/Documents/scientific-conferences/Tau-Agenda_Alzheimers-Association.pdf?_gl=1*1uer3x5*_ga*MTI4OTUzNzIwMS4xNjk5Mjg1OTY3*_ga_QSFTKCEH7C*MTcwMzc5MTI5Mi43LjEuMTcwMzc5MjUxNS42MC4wLjA.*_ga_9JTEWVX24V*MTcwMzc5MTI5Mi43LjEuMTcwMzc5MjUxNS42MC4wLjA.
I don't see U. of Wisconsin and or Carol Van Hulle/Cynthia Carlsson as a presenter, although I don't know when this document was posted or if the presenters correspond to accepted abstracts. They were accepting abstracts up until Dec 5th 2023, and apparently would notify the acceptance decision end of December.
https://www.alz.org/media/Documents/scientific-conferences/Tau-2024_Call-for-Papers_Alzheimers-Association.pdf
If in fact Brave is not being presented at this conference, that might be supportive of the hypothetical situation you posed. To be very clear, I still think there's enormous value in Amarin without Brave.
FDA publishing pre-notices of noncompliance to clinical trial sponsors.
We'll should see MITIGATE on this list if results are not posted soon to clinical trials.gov. They might've filed for a time extension though
https://www.fda.gov/science-research/fdas-role-clinicaltrialsgov-information/pre-notices-potential-noncompliance
https://www.statnews.com/pharmalot/2023/12/14/fda-nih-clinical-trial-transparency/
Agreed. Sleven has only been a constructive poster, and has also been doing DD on Brave for years.
For my part, I didn't realize Sleven was working with new information (albeit not fully confirmed), and is trying to find out more. Unfortunately for us retail investors, we have to fight for every ounce of intel, so I appreciate Sleven sharing and would very much prefer he continues posting.
If Brave is truly a cleanly null result, perhaps we can add it to our bundle of evidence that mineral oil placebo isn't detrimental.
I agree. I believe there were emails from Hannah Zylstra (Brave clinical coordinator) to multiple people on both Ihub and stocktwits confirming Brave data hasn't been fully processed, and that they were potentially looking to present at a conference a few months out.
Pdude opined a while ago they likely scheduled this conference way in advance, without knowing if they'll be ready or not with results.
Sleven, correct me if i'm wrong, but this seems like old news? I recall all of us discussing this back in November, and the conclusion was that it's likely nothing material was presented at that conference and results are still be processed at that time.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=173156717
Interestingly, in the >500 Trigs study in China, apparently there was 1 case of acute pancreatitis that happened to occur in the 4g IPE arm, while none in the placebo.
"Due to TEAEs, three patients in the IPE 4 g/day group (2.4%; one patient each with abnormal hepatic function, urticaria, and severe pancreatitis) and one patient in the placebo group (0.8%; hypersensitive response) terminated the trial. "
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257163/