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Ridker is advocating for Esperion’s BA (Bempedoic Acid - Nexletol) and was lead author of recent CLEAR harmony paper
https://pace-cme.org/bempedoic-acid/
https://www.sciencedirect.com/science/article/abs/pii/S1933287423000326
Journal of Clinical Lipidology
Available online 14 February 2023
Effects of bempedoic acid on CRP, IL-6, fibrinogen and lipoprotein(a) in patients with residual inflammatory risk: A secondary analysis of the CLEAR harmony trial
Paul M Ridker MD, Lei Lei PhD, Kausik K. Ray MD, Christie M. Ballantyne MD, Gary Bradwin MS, Nader Rifai PhD
This study was sponsored by Esperion Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02666664; https://clinicaltrials.gov/ct2/show/NCT02666664.
CRP More Predictive of Future Events Than LDL in Statin-Treated Patients
An adjuvant anti-inflammatory might offer more protection than additional lipid-lowering, a meta-analysis hints.
MARCH 14, 2023
https://www.tctmd.com/news/crp-more-predictive-future-events-ldl-statin-treated-patients
More than half of the trial participants had hsCRP ≥ 2 mg/L. This criterion alone put them at greater risk of MACE, CV death, and all-cause death, irrespective of whether they had an LDL cholesterol ≥ 70 mg/dL.
“While these data must not be construed to diminish the proven and crucial role of adjunctive lipid-lowering for those with persistent or refractory health hypercholesterolemia, our data do suggest that targeting of LDL alone is unlikely to completely reduce atherosclerotic risk and that inflammatory pathways have yet to be fully exploited to really address this issue,” Ridker concluded.
“I would argue, as I have for quite a few years, [that] we all should be measuring CRP,” Ridker concurred. “We measure LDL so we know what we’re doing. We measure blood pressure so we know what we’re doing. If you’re not measuring CRP, you have no idea that your patient even has this problem, and clearly in these 32,000 patients this was rather important.”
…
———————
Ridker doesn’t mention Vascepa/IPE as a treatment option although it is the drug used in one of three trials in meta-analysis! He was also lead author of the biomarkers analysis that Bhatt & others said reviewers/editors blocked inclusion of important additional analysis from. Perhaps the recently presented favorable hsCRP data is part of the blocked added analysis? Seems Ridker has a bias against IPE.
dogn
New Study Indicates Inflammation Could Be Major Driver of Atherosclerotic Risk
Mar 9, 2023
https://www.hcplive.com/view/new-study-indicates-inflammation-could-be-major-driver-of-atherosclerotic-risk
An analysis of the PROMINENT, REDUCE-IT, and STRENGTH trials provides insight into the atherosclerotic cardiovascular risk associated with high-sensitivity C-reactive protein.
one more...
https://medwatch.com/News/hearing_health/article15342694.ece
15/03/2023 at 11:16
HEARING HEALTH
Departing GN chair: An organizational split would be unwise
Per Wold-Olsen, who is stepping down as chairman of GN Group today, says that competitors have started copying the company’s unique business model.
https://photos.watchmedier.dk/watchmedier/resize:fill:1080:0:0/plain/https://photos.watchmedier.dk/Images/15342219/wk6imh/ALTERNATES/schema-16_9/GN-billede3.jpeg
Per Wold-Olsen speaking at GN Group's AGM in Ballerup, Denmark | Photo: Christopher Due Karlsson
BY CHRISTIAN BUNDGAARD, CHRISTOPHER DUE KARLSSON & STINE LØCKE NIELSEN, TRANSLATED BY DANIEL PEDERSEN
It didn't take long before outgoing chairman of GN Group, Per Wold-Olsen, took to the podium at the company's annual general meeting, which was held on Wednesday. Here, he addressed the rumors about GN Group's future.
[rest of article behind paywall]
GN chairman: "Many external factors affected the company last year"
MarketWire
Wednesday 15 March 2023 at 10:38
https://ugebrev.dk/marketwire/gn-formand-mange-eksterne-faktorer-ramte-selskabet-sidste-aar/
via Google translate
GN had a difficult 2022 – both when it comes to the financial results and the share price, which during the year fell by a good 61 per cent.
And it was a large number of external factors that gave headwinds on the cycle path and hit GN, according to the company's outgoing chairman of the board, Per Wold-Olsen, in connection with Wednesday's ordinary general meeting.
However, he feels convinced that GN must also get back on track and be able to create positive returns for the shareholders, he says in an introductory speech in connection with the general meeting.
- There were an incredible number of external factors that gave GN significant headwinds in 2022. First of all, the terrible war in Ukraine, which affected us all in one way or another. It has also led to sky-high inflation in large parts of the world, and we have seen a sharp decline in consumer confidence. We are still waiting to see if the world will be hit by a real recession. Covid-19 disruptions also still affected – not least in China. We experienced continued disruptions in the supply chains, and we had to pay very high prices for transport, says Per Wold-Olsen.
- Despite the quite strong headwinds and the external circumstances, the business still delivered a turnover of DKK 18.7 billion. DKK and an adjusted operating result (EBITA) of approximately DKK 2.2 billion. DKK. The organic growth was negative, which of course none of us likes to see. But compared to the external headwinds we were working under, we got away relatively easily, the chairman continues.
HAS EXPERIENCED MANY CRISES IN HISTORY
As a company, GN has more than 150 years behind it, and throughout its long history the company has experienced a large number of different crises.
But unlike in the past, GN is today better equipped to make a strong comeback, reads the assessment from Per Wold-Olsen.
- This company has been in crisis many times in its more than 150-year history. At the latest in 2008/09, when the whole world went through a serious financial crisis, there was a crisis in GN. Back then, it wasn't just the economy that caused problems, but also GN itself. GN did not function as a professional company, says the chairman of the board, who is expected to be replaced by Jukka Pekka Pertola in connection with Wednesday's general meeting.
- Today, GN is a professional and well-run company that stands out with a unique profile. The markets we operate in have been declining in the short term, but we feel very confident that they will come back strongly – and as a result our ability to generate returns for shareholders, says Per Wold-Olsen.
.\\? MarketWire
Per Wold-Olsen stepped down as GN Store Nord chairman of the board at today's general meeting.
https://www.euroinvestor.dk/nyheder/gn-formands-afsked-blev-overskygget-af-heftig-kritik-jeg-er-fandeme
via Google translate
NEWS
March 15 2023 - 16:21
The GN chairman's resignation was overshadowed by fierce criticism: 'I'm damn disappointed'
Sigurd Pedersen
Despite 15 years in the post, GN 's chairman's resignation was overshadowed by criticism and takeover speculation.
On Wednesday, the shareholders in GN Store Nord had to say goodbye to long-standing board chairman Per Wold-Olsen. However, it was not the big and touching farewell that the outgoing chairman might have hoped for.
The farewell was overshadowed by the recent actions of the GN Store Nord board.
The board had proposed a capital increase on 9 February, but on Tuesday – less than a day before the general meeting – the board withdrew the proposal.
Read also: Shareholders' association thunders against the GN board at the general meeting
The reason was that it was already clear from the votes cast in advance that the proposal would not achieve the necessary support.
Although the proposal was withdrawn, it did not prevent several shareholders from taking to the podium to criticize the proceedings.
Per Wold-Olsen had started the meeting by talking about the year 2022, which GN Store Nord had escaped well, according to him, despite headwinds from external factors.
This got one of the shareholders up in the red.
"You shouldn't sit and praise yourself. I'm damn disappointed as a shareholder,' said the shareholder from the podium.
The shareholder was very dissatisfied with the price development for GN Store Nord , which has fallen by around 25 per cent. since the board proposed the controversial capital increase. The shareholder continued his criticism with several profanities along the way.
It was a clearly moved Per Wold-Olsen who responded after the shareholder's great criticism.
Read also: GN chairman puts words to the speculation: We do not want to sell
"We are all dissatisfied with the price development," said Per Wold-Olsen to the shareholder.
The voice broke during the outgoing board chairman's answer, but the criticism of the board's direction did not stop there.
The outgoing chairman of the board had previously rejected the idea of a full or partial sale to the competitor Demant at the general meeting.
However, that line was also criticized by a shareholder from the podium.
"No company lives forever. If we can get involved in something bigger, we must do it,' said a shareholder on the platform.
It was a comment that brought applause from many of those present.
Read also: Tordner against GN: They didn't think about the shareholders
A possible sale to the competitor was brought up by several shareholders along the way, and it was met with applause each time. However, not everyone applauded it.
A more personal attack came from a member of the Danish Shareholders' Association's general meeting committee, Søren Svendsen.
He highlighted that the market had welcomed the news of the chairman's departure, which was announced on 26 January. On the same day, the share rose by more than 10 per cent.
However, Søren Svendsen rounded off by thanking Per Wold-Olsen for his efforts for GN Store Nord over many years.
The entire general meeting was also rounded off with a round of applause in honor of the outgoing chairman. It was a brief round of applause that sent Per Wold-Olsen on to the world after 15 years as chairman of GN Store Nord .
COWEN ANNUAL HEALTH CARE CONFERENCE
Mar 8, 2023 at 1:30 PM EST
https://investor.amarincorp.com/events/event-details/cowen-annual-health-care-conference
While looking at the TA charts and “wondering why the price has just traced an ominous triple top”, can you explain how this price action “reality” can reasonably ignore unique real world & significant external events that may completely alter the future trajectory of the company? Curious how you accept a seemingly total lack of awareness with TA of what’s driving the price up & down at each point… eg uncertainty regarding who wins the proxy, whether forward path continues to be GIA or packaging for a sale? I believe TA can be a useful tool, and enjoy your charts, but not when used while blind to other real world events to sow fear and doubt, which I still perceive as your aim.
Recalling this, 2 days before proxy win announcement, Sarissa’s previous PR:
https://www.businesswire.com/news/home/20230227005345/en/Sarissa-Capital-Condemns-Amarin-Board-for-Frontrunning-Results-of-Proxy-Contest-With-Egregious-Equity-Grants-to-Executives
makes today’s resignations seem like a direct result of Sarissa holding these 7 accountable as was foreshadowed:
“Bear in mind that at last year’s annual meeting more than a majority of the outstanding stock either abstained or voted against “Say on Pay,” yet this board determines to change the timing of and significantly increase the quantum of executive equity grants. We believe the answer is simple — this board is violating its fiduciary duties and applicable law. Accordingly, we intend to hold each director personally liable to the fullest extent permissible under applicable law.”
Site I use for tracking after hours price & volume
https://www.marketwatch.com/investing/stock/amrn
All relevant ACC abstract & links
Mar. 4, 2023, 9:45 AM - 9:55 AM
1008-03 - SERUM LEVELS OF EICOSAPENTAENOIC ACID BUT NOT DOCOSAHEXAENOIC ACID CORRELATE WITH REDUCTION IN CORONARY LIPID PLAQUE VOLUME IN PATIENTS ON STATIN OR STATIN PLUS OMEGA-3 FATTY ACID THERAPY
John Patrick Sheppard, Suvasini Lakshmanan, Sion Roy, Deepak L. Bhatt, Matthew J. Budoff, John R. Nelson, Yale New Haven Hospital, New Haven, CT, USA, Lundquist Institute/Harbor-UCLA Medical Center, Torrance, CA, USA
https://www.abstractsonline.com/pp8/#!/10674/presentation/10774
Mar. 4, 2023, 10:45 AM - 11:30 AM
1255-029 - EICOSAPENTAENOIC ACID (EPA) MODULATED EXPRESSION OF PROTEINS LINKED TO PLATELET ACTIVATION AND THROMBOSIS IN VASCULAR ENDOTHELIAL CELLS DURING INFLAMMATION
Samuel CR R. Sherratt, Peter Libby, Deepak L. Bhatt, R. Preston Mason, Elucida Research, Beverly, MA, USA
https://www.abstractsonline.com/pp8/#!/10674/presentation/20318
Mar. 5, 2023, 10:21 AM - 10:31 AM
909-08 - BENEFITS OF ICOSAPENT ETHYL IN PATIENTS WITH RECENT ACUTE CORONARY SYNDROME (ACS): REDUCE-IT ACS
Philippe Gabriel Steg, Deepak L. Bhatt, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Steven Ketchum, Lixia Jiao, Armando Lira Pineda, Ralph T. Doyle, JR, Jean Claude Tardif, Christie M. Ballantyne, the REDUCE-IT Investigators, Brigham and Women's Hospital, BOSTON, MA, USA
https://www.abstractsonline.com/pp8/#!/10674/presentation/10983
Mar. 6, 2023, 9:45 AM - 10:30 AM
1691-005 - COMPARING THE EFFECTS OF PHARMACEUTICAL GRADE MINERAL OIL, CORN OIL, EICOSAPENTAENOIC ACID (EPA) AND DOCOSAHEXAENOIC ACID (DHA) IN A MODEL OF ATHEROSCLEROSIS IN VITRO
Samuel CR R. Sherratt, Peter Libby, Deepak L. Bhatt, R. Preston Mason, Elucida Research, Beverly, MA, USA
https://www.abstractsonline.com/pp8/#!/10674/presentation/17061
Mar. 6, 2023, 10:00 AM - 10:10 AM
1082-05 - PHARMACEUTICAL GRADE MINERAL OIL AND CORN OIL DO NOT INFLUENCE PHOSPHOLIPID MEMBRANE OXIDATION RATES COMPARED TO OMEGA-3 FATTY ACIDS IN VITRO
Samuel CR R. Sherratt, Peter Libby, Deepak L. Bhatt, R. Preston Mason, Elucida Research, Beverly, MA, USA
https://www.abstractsonline.com/pp8/#!/10674/presentation/11360
Mar. 6, 2023, 1:00 PM - 1:10 PM
411-10 - Residual Inflammatory Risk In Contemporary Statin Treated Patients: A Collaborative Analyses Of 31,197 Participants In The Prominent, Reduce-it, And Strength Trials
Paul M. Ridker, Aruna Das Pradhan, Deepak L. Bhatt, Steven E. Nissen, on behalf of the PROMINENT, REDUCE-IT, and STRENGTH Investigators, Brigham and Women's Hospital, Boston, MA, USA
https://www.abstractsonline.com/pp8/#!/10674/presentation/20488
Session 411 - Featured Clinical Research III
411-10 - Residual Inflammatory Risk In Contemporary Statin Treated Patients: A Collaborative Analyses Of 31,197 Participants In The Prominent, Reduce-it, And Strength Trials
March 6, 2023, 1:00 PM - 1:10 PM La Nouvelle B
Authors
Paul M. Ridker, Aruna Das Pradhan, Deepak L. Bhatt, Steven E. Nissen, on behalf of the PROMINENT, REDUCE-IT, and STRENGTH Investigators, Brigham and Women's Hospital, Boston, MA, USA
Abstract
Abstract is embargoed at this time.
https://www.abstractsonline.com/pp8/#!/10674/presentation/20488
http://investor.amarincorp.com/ still takes you to the “old & improved” website (& still shows current info).
Here’s page with link to tomorrow’s earnings webcast:
https://investor.amarincorp.com/events-and-presentations/events
Direct link: https://www.webcaster4.com/Webcast/Page/2037/47584
dogn
Mitigate - today is “Estimated Study Completion Date”
No clue when results will be made public
https://clinicaltrials.gov/ct2/show/record/NCT04505098
Estimated Study Completion Date
February 28, 2023
Estimated Primary Completion Date
February 28, 2022 (Final data collection date for primary outcome measure)
FFS, you say
As both white & blue cards are now universal proxy cards (UPCs), I gather the only difference is recommendations on how to vote (Amarin on white card recommends voting AGAINST all proposals; Sarissa on blue card recommends voting FOR all proposals), but it seems with UPCs, anyone can vote as they choose on either card. I’ve just been pondering this because I have Fidelity documents eDelivery & always vote online through proxyvote.com, which Fidelity provides a link to (still not available). So I’ve been wondering if & how these two separate colored proxy “cards” will appear electronically.
Following “The Second Universal Proxy Card Hits EDGAR” by Michael R. Levin
3 months ago
https://clsbluesky.law.columbia.edu/2022/10/26/the-second-universal-proxy-card-hits-edgar/
notes “Why would each acknowledge that shareholders might vote for the other’s nominees, and suggest they could do so using their own proxy card? We’d think they would do everything it could to discourage this.
It appears each wants to receive as many proxy cards as it can. They can thus track which shareholders have already voted. If AIM receives proxy cards with votes for L&B nominees, and L&B for AIM nominees, then each can easily contact those shareholders, and attempt to persuade them to change their votes. Clever…”
So apparently votes are tracked in real time as they come in and perhaps only Amarin sees white card votes & only a Sarissa sees blue card votes from their separate proxy card solicitors? So they may each want you to vote on their card to track how they’re doing…and prevent other party from knowing your vote until the meeting?
What the Universal Proxy Card Means for Directors
September 1, 2022
https://blog.nacdonline.org/posts/universal-proxy-card-directors
What is the practical effect of the universal proxy on negotiations with activists?
One concern is that the rule change will make it more difficult to come to a reasonable, amicable resolution with activists. If activists expect they will win one or two seats anyway and are able to threaten to take control of the board, they will believe they have more leverage. There also appears to be almost no downside to “over nominating” a large slate of candidates that is disproportionate to the case for change. This in turn will make it harder to achieve a limited settlement with activists.
ISS Provides Guidance on the Universal Proxy Card, Puts “Weakest” Directors on Notice
From Proxy advisor Institutional Shareholder Services
August 24, 2022
https://www.sidley.com/en/insights/newsupdates/2022/08/iss-provides-guidance-on-the-universal-proxy-card-puts-weakest-directors-on-notice
As discussed in a previous Shareholder Activism Update (https://www.sidley.com/en/insights/newsupdates/2021/11/sec-dramatically-changes-the-rules-for-proxy-contests), the new rules have the potential to lead to increased proxy contest threats and less challenging campaigns for activists.
The second prong — “how much change?” — will come into sharper focus, given that shareholders will now be able “to more precisely adjust board composition.” ISS expects activist slates to be “proportionate” to the issues identified by the activist and implicitly cautions activists not to overreach in the number of directors they nominate, noting that doing so could “backfire” by undermining the overall quality of the dissident slate.
More videos, now from Amarin board members
https://www.youtube.com/@amarin-corporation/videos
Lizzy,
This website https://investor.amarincorp.com/financial-information/sec-filings I think shows the latest filings on top… the one you refer to, Sarissa’s PRRN14A seems to have been filed after Amarin’s DEFC14A which is definitive. I found that interesting.
Looking at EDGAR time stamps from “Filing” links at https://www.sec.gov/edgar/browse/?CIK=897448&owner=exclude
DEFC14A Accepted 2023-01-31 07:59:59
https://www.sec.gov/Archives/edgar/data/897448/000119312523019715/0001193125-23-019715-index.htm
shows Amarin’s was filed after Sarrisa’s
PRRN14A Accepted 2023-01-31 06:02:40
https://www.sec.gov/Archives/edgar/data/897448/000114036123003464/0001140361-23-003464-index.htm
dogn
ggwpq, I did see that Glass Lewis has supported Sarissa nominees in past proxy wars (March 2017 against Innoviva). But haven't seen GLO on Sarissa's other activist investments.
https://www.prnewswire.com/news-releases/glass-lewis-supports-sarissa-capitals-nominees-for-innoviva-board-300436088.html
I agree, but think Sarissa didn’t argue with this voting solution proposed by Amarin because they are confident POW WILL be voted out making it unlikely that Diana Sullivan will get the short end of the stick
Incorrect interpretation… only last of 7 candidates, Diana Sullivan (unfortunately last by alphabetical order) would not be put forth for a vote… that’s how I read it.
Thank you for your post. As you agree with PharmacyDude & other’s preference for “not more than 2-3 seats,” how would you see this happening apart from the BOD settling with AD before the vote (and is this getting at you mean by their not seeing the forest for the trees)? If it goes to a vote, even though proxy has been corrected to put forth individual votes on each of the 7 Sarissa candidates, voters will all likely pull the “straight ticket” levers - I can’t see retail holders or proxy advisers successfully advocating for just 2 or 3 preferred candidates.
PDude wrote “Bottom line: I want AD on the Board just not more than 2-3 seats (every seat will cost half million share dilution)” yet AD himself is not one of the 7 candidates, so I assume that we just mean here Sarissa representation. I speculate that part of their strategy is that if POW is removed and all 7 elected, they could then appoint AD as new COB (or at least the threat of this possibility is the reason to put forth 7, to increase negotiating leverage).
Regarding what others have noted as a Jan. 23 share ownership recording date, this date appears only in a “draft” “Proxy soliciting materials. Revised preliminary material proxy statement form PRER14A” filed on Jan. 27, and a second, assumed later one on Jan. 27 (at top in list at https://investor.amarincorp.com/financial-information/sec-filings) still has no Date information: https://investor.amarincorp.com/sec-filings/sec-filing/prer14a/0001193125-23-016842
dogn
Aren’t we all
wallmine clearly has some inaccuracies, stating at one spot that on 13 June 2022 POW bought 55,000 shares of GILD, in another that it was 55,000 of AMRN.
https://wallmine.com/people/10880/olsen-per-wold
Assuming the latter is correct, and going by the wallmine info at end of linked page, here is total value of POW's holdings for both compared to Sarissa Capital:
FWIW, Recalculating total value with TODAY'S closing prices:
Market value of Per Wold-Olsen holdings:
AMRN 55,000 shares @ $1.80 = $99,000
GILD 102,060 shares @ $83.23 = $8,494,454
Market value of Sarissa Capital holdings from whalewisdom:
AMRN 25,210,000 shares @ $1.80 = $45,378,000
GILD 1,273,100 shares @ $83.23 = $105,960,113
PWO retired from GILD BOD effective annual meeting of May 12, 2021.
https://www.sec.gov/Archives/edgar/data/882095/000120677421000908/gild3818501-def14a.htm#CorporateGovernanceHighlights
"Richard J. Whitley, M.D., and Per Wold-Olsen are retiring effective at the Annual Meeting, and our Board size will be reduced from eleven to nine members effective after the conclusion of the Annual Meeting, provided that our director nominees are elected by stockholders at the Annual Meeting."
GILD is Sarrisa Capital's 4th largest holding
https://whalewisdom.com/filer/sarissa-capital-management-lp#tabholdings_tab_link
with "Qtr 1st Owned" of Q1 2021.
From same GILD proxy statement, Stock Ownership Information:
Per Wold-Olsen 179,878 shares (with footnote: Includes 79,754 shares subject to stock options exercisable within 60 days of February 26, 2021.)
Thanks for this information, North. Would love to see JPM upgrade to buy Monday morning.
Ropes & Gray LLP is a separate law firm from the other… there are 2 involved, 2 that have partnered on 2 $1.5B M&A deals I saw just last year (see my prior post).
https://www.ropesgray.com/en/newsroom/rankings-awards/2022/11/ropes-gray-named-the-american-lawyers-law-firm-of-the-year-honored-for-life-sciences-and-health-care
I think you are likely correct that behind the scenes different parties may favor different potential, eventual BP suitors (Pfizer who sells Vascepa in Canada, Novartis to whom Denner orchestrated sale of The Medicines Company, Merck where PWO and KM once worked, Bristol Myers Squib where Deepak Bhatt recently joined board, etc.). We don’t know 1% of all the jockeying going on. Each has different timelines, price targets, trigger milestones to first meet.
It interested me recently to see Denner’s mentor Carl Icahn 5 years ago took an undisclosed stake in BMY https://www.wsj.com/articles/carl-icahn-takes-stake-in-bristol-myers-squibb-1487710151, with speculation then that they may be sold to Pfizer, Gilead Sciences (where POW was then on the board), Novartis AG or Roche. https://www.biospace.com/article/serial-investor-b-carl-icahn-b-takes-stake-in-bristol-myers-squibb-stock-jumps-/
Gilead didn’t buy BMY - is this connected to Denner’s disdain for POW… all baseless speculation on my part, but I have to believe there are such things at play.
This fight may be more about which BP gets the prize that is Vascepa and at which price than how soon AMRN ends playing the game “it’s GIA (until it’s not).”
AMRN may be forced to disclose what non-GIA plans they are entertaining while pretending it’s GIA or bust if they hope to win a proxy battle. Nobody wants to show their cards, but how else can they convince shareholders their preferred suitor provides a greater return.
Otherwise, settle with Denner winning some board representation, and likely POW stepping down, before it gets to that. Because with the overwhelming support voiced here for Sarissa, it seems they have much more to lose if they enter the ring. It would seem if there are well evaluated reasons to believe one path is more lucrative, all parties should openly listen to each other’s ideas. Unfortunately it probably comes down to greed as in one’s path is more lucrative to said party than to the other.
It’s very hard to discount the arguments that current management wants the path that keeps feeding them free shares. They could counter that by enacting different performance-based compensation policies.
dogn
It on one hand appears favorable that the company is being advised by the street’s top bank, but on the other hand inconceivable that we see no direct measures of obvious support (an investment stake, an analyst upgrade). How can mgmt ask us to support them when JPM will not? They certainly have the resources and influence to impact shareholder opinion if they choose to. Without such their financial advice is open to skepticism.
Puzzled by stance and role of J.P. Morgan & new legal advisors
Just some observations I've been mulling about. Anyone else notice or have thoughts on this? I've not seen discussed the following
STS, I share your thinking & concerns. Thanks for stating them so clearly and eloquently.
dogn
American College of Cardiology 2022 Top Journal Scans & Clinical Trials
Dec 23, 2022 ACC News Story
https://www.acc.org/Latest-in-Cardiology/Articles/2022/12/15/01/2022-Top-Clinical-Trials-and-Journal-Scans
Top Clinical Trials
Deepak L. Bhatt, MD, MPH, FACC
Senior Associate Editor, Clinical Trials and News, ACC.org
Under "Top Clinical Trial Updates"
REDUCE-IT (Update): Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial
Highlighted text has been updated as of August 26, 2022.
Reduction in MI: Overall MI incidence for IPE vs. placebo: 8.6% vs. 12.0% (p < 0.0001); ST-segment elevation MI (STEMI): 2.7% vs. 3.9% (p = 0.0008); NSTEMI: 5.9% vs. 7.8% (p = 0.001); fatal or nonfatal MI: 6.1% vs. 8.7% (p < 0.0001). At least one bleeding event among STEMI patients: 19.4% vs. 14.5% (p = 0.41).
References:
Presented by Dr. Deepak Bhatt at the European Society of Cardiology Congress (ESC 2022), Barcelona, Spain, August 26, 2022.
Eicosapentaenoic acid vs. docosahexaenoic acid for the prevention of cardiovascular disease
Current Opinion in Endocrinology, Diabetes & Obesity
https://pubmed.ncbi.nlm.nih.gov/36562280/
Dec. 26, 2022 doi: 10.1097/MED.0000000000000796. Online ahead of print.
Ty E Sweeney, Sean P Gaine, Erin D Michos
Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Abstract
Purpose of review: Populations with greater fatty fish intake have lower risk of coronary heart disease. However, trials testing omega-3 fatty acids (FA) on cardiovascular outcomes have yielded inconsistent results. In this review, we summarize the major cardiovascular trials examining omega-3 FA supplementation, and compare differences with eicosapentaenoic acid (EPA) alone vs. docosahexaenoic acid (DHA) combined with EPA.
Recent findings: The JELIS and REDUCE-IT trials both demonstrated significant reduction in cardiovascular events with high dose EPA in the form of icosapent ethyl (IPE), with a similar trend seen in the RESPECT-EPA trial. In contrast, the ASCEND, VITAL, STRENGTH, and OMEMI trials examining EPA+DPA combinations failed to demonstrate benefit. Beyond the difference in omega-3 FA formulations (IPE vs. omega-3 carboxylic acid), other differences between REDUCE-IT and STRENGTH include the achieved EPA levels, differing properties that EPA and DHA have on membrane stabilization, and the comparator oils tested in the trials.
Summary: The totality of evidence suggests EPA alone, administered in a highly-purified, high-dose form, improves cardiovascular outcomes among patients with elevated triglycerides at high cardiovascular risk, but EPA and DHA together does not. Current guidelines endorse the use of IPE in statin-treated patients at high cardiovascular risk who have triglycerides >135 mg/dl.
Emphasis on Icosapent Ethyl for Cardiovascular Risk Reduction: A Systematic Review
Cureus Open Access Review Article published December 09, 2022
https://www.cureus.com/articles/114415-emphasis-on-icosapent-ethyl-for-cardiovascular-risk-reduction-a-systematic-review
DOI: 10.7759/cureus.32346
Cite this article as: Sutariya B, Montenegro D M, Chukwu M, et al. (December 09, 2022) Emphasis on Icosapent Ethyl for Cardiovascular Risk Reduction: A Systematic Review. Cureus 14(12): e32346. doi:10.7759/cureus.32346
37 articles were reviewed and 12 articles (One Non-Randomized Clinical Trial, Three Systematic Reviews, Three Randomized Controlled Trials, and Five Reviews) were included in the review
Abstract
Despite the widespread use of lipid-lowering agents such as statins, cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Icosapent ethyl (IPE) (Vascepa), an ethyl ester of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), has gained widespread popularity as an adjunctive agent that targets multiple and additional mechanisms linked to the incidence of cardiovascular (CV) events and the causative pathway of atherosclerosis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 standards were used to conduct this systematic review. In this review, we assessed various studies from PubMed, PubMed Central (PMC), and Google Scholar to evaluate the mechanisms of action and beneficial effects of IPE in the reduction of CVD outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) has demonstrated a significant reduction in CV mortality with 4 g/day IPE as compared to placebo. All other trials and observational studies have supported the role of Vascepa in hypertriglyceridemia and CV risk reduction. In conclusion, the use of IPE has been shown to significantly reduce triglyceride levels and reduce CV risks in patients receiving optimal statin therapy.
Introduction & Background
According to the 2017 Global Burden of Diseases, Injuries, and Risk Factors Study, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality worldwide and poses a significant danger to global health [1,2]. Cardiovascular disease was responsible for over 17.8 million deaths in 2017, and by 2030, that number is anticipated to rise to 22.2 million [3]. An estimated 18.2 million Americans over the age of 20 have coronary artery disease, and 7.0 million have had a stroke [4]. While the widespread use of statins in primary and secondary prevention has greatly improved cardiovascular (CV) outcomes, a substantial residual CV risk remains elevated despite such evidence-based lipoprotein lowering treatment and may require additional therapy to lower this risk [3,5]. Several studies have demonstrated a causal link between high triglyceride (TG) levels and residual CV risks [6-9]. Prior medications targeting TG levels or high-density lipoprotein cholesterol levels, such as fibrates and niacin, have not sufficiently reduced adverse outcomes [3]. That emphasizes the need of identifying a medication that targets multiple and additional mechanisms linked to the incidence of CV events and the causative pathway of atherosclerosis [10].
Icosapent ethyl (IPE) has gained significant recognition as an additive agent recently. IPE is an ethyl ester of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) that works in the manner of a plasma-binding protein in the blood [11]. Through its effects on the onset of plaque development and plaque rupture, EPA plays a beneficial role in the pathophysiologic cascade of plaque development [12]. A number of specific salutary actions on atherosclerotic plaque factors have been reported including antioxidant effects, anti-inflammatory effects, decreased macrophage accumulation, improved endothelial function, decreased foam cell accumulation, decreased adhesion of monocytes, increased fibrous-cap thickness, and an increase in resolvins, a class of pro-resolving lipid mediators [10,13,14]. EPA is scientifically plausible as a potential anti-atherosclerotic agent based on mechanistic, pathophysiologic, outcomes, and plaque-imaging studies [12].
The IPE compound within the drug known as Vascepa has been shown to decrease the plasma level of atherogenic parameters such as TGs, non-high-density lipoprotein cholesterol (non-HDL-C), oxidized low-density lipoprotein particles (ox-LDL), and remnant cholesterol remnant-like particle cholesterol (RLP-C) without raising low-density lipoprotein cholesterol (LDL-C) levels in patients with very high TG levels and statin-treated patients with high TG levels and high residual CV risk [15,10,13]. Significant reductions in important ischemic events were reported with IPE in the international, double-blind, randomized, placebo-controlled Reduction of Cardiovascular Events with Icosapent Ethyl Intervention Trial (REDUCE-IT) study [16]. The primary endpoint (composed of CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization), the important secondary endpoint (composed of CV death, nonfatal myocardial infarction, or nonfatal stroke), and individual components of those endpoints all had lower incidences following IPE treatment [16,17]. Since the publication of REDUCE-IT, the usage of IPE has been recommended by the American Diabetes Association (ADA), National Lipid Association (NLA), and the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), to further decrease ASCVD risk in selected patients [18]. In this systematic review, we will summarize the clinical benefits of IPE and its role in CV risk reduction.
[See link for detailed Review Methods, Results, Discussion, Limitations sections]
Conclusions
IPE, a novel FDA-approved agent, has been proven effective in significantly lowering TG levels and reducing CV risks in patients who are already on optimal statin therapy. Although its mechanisms have yet to be fully explained, IPE, being the first drug of its class to be approved, is believed to exert its cardioprotective effect through its anti-inflammatory and anti-thrombotic properties. From a deeper comprehension of the chemical mechanism of action to practical application and cost-effectiveness, there is still much to learn about IPE. In summary, we herein support the consideration of IPE as an important adjunct therapy for the reduction of residual ASCVD risk in high-risk patients already on statin therapy.
Deepak Bhatt makes the case that RESPECT-EPA was a "positive trial"
From MedpageToday on Dec. 6
https://www.medpagetoday.com/meetingcoverage/ahavideopearlslipidmanagement/102089
"Icosapent Ethyl Linked to Reduced Risk of Cardiovascular Events"
— Deepak Bhatt, MD, MPH, makes the case that RESPECT-EPA was a "positive trial"
by Greg Laub, Director, Video, MedPage Today December 6, 2022
Use of icosapent ethyl (Vascepa), a highly purified eicosapentaenoic acid (EPA), may be associated with a reduction in risk of adverse cardiovascular events in Japanese patients with chronic coronary artery disease (CAD) who were also being treated with statins, according to results from the RESPECT-EPA trial presented at the American Heart Association annual meeting.
In this video, Deepak Bhatt, MD, MPH, the director of Mount Sinai Heart at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Health System in New York City, discusses the study.
Following is a transcript of his remarks:
This was a study done in Japan, randomization to 1.8 g a day of icosapent ethyl versus not. That's what open label means, that there wasn't a matching placebo, but it was randomized. These were patients, again from Japan, who had known cardiovascular disease, but actually who ended up having essentially normal triglycerides, unlike say, REDUCE-IT, where everyone had high triglycerides. And these were patients with, I'd say, reasonably well controlled LDL average -- LDL baseline was like 80 mg/dL or something like that.
So these patients were randomized, it was a bit of an underpowered study outta the gate, about 1,200 or so patients in each arm. So, perhaps a bit optimistic in terms of powering in this trial as well. But the overall primary endpoint was a composite of cardiovascular death, nonfatal MI, nonfatal ischemic stroke, unstable angina, coronary revascularization.
And I'll say the primary endpoint was met, but, you know, one could quibble about the statistics. The P value was 0.054, the upper bound of the 95% confidence interval was 1.001, I think. So, one could say, strictly speaking, that's not a statistically significant value because it's not 0.05 or less. But again, I thought pretty close for that primary endpoint -- a hazard ratio of 0.785.
The secondary endpoint, which was sudden cardiac death, MI, unstable angina, coronary revascularization, there, the hazard ratio was 0.73. There, the P value was 0.03. So that was clearly statistically significant. Looking at the Kaplan-Meier curves for both the primary endpoint and the secondary endpoint, it was clear that a few years after randomization, the curves were clearly separating.
So, my assessment was that it was a positive trial, that there's something there that, in this population, this dose worked.
I'll just point out, compared with REDUCE-IT, this was a lower dose of icosapent ethyl, 1.8 g a day, REDUCE-IT used 4 g total per day. As well, these are Japanese patients and their EPA levels are higher than in Western populations. They did do some sort of enrichment here based on EPA:AA ratio, but even still their levels are like an order of magnitude higher than in Western populations. And I think the lack of high triglycerides here, I mean, that's a powerful risk factor. One can debate whether it's a modifiable risk factor per se, but for sure if your trigs are elevated despite statin and dietary counseling, you're at higher risk. So, much lower risk population than REDUCE-IT.
But, qualitatively, in other, I'd say, positive trials, much like JELIS (Japan EPA Lipid Intervention Study), a prior Japanese trial, also open-label with some limitations, but there as well a hazard ratio that favored the study drug. Once more, that was a lower dose, 1.8. So, to me, you know, it's a consistency across multiple different trials. And, you know, I think there's something there to EPA-based therapy.
Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.
RESPECT-EPA story published today (Editor's pick in Hospital Pharmacy Europe): Highly purified EPA decreases adverse cardiovascular events in patients with CAD" https://hospitalpharmacyeurope.com/news/editors-pick/highly-purified-epa-decreases-adverse-cardiovascular-events-in-patients-with-cad/