Amarin - The Science Of Lipid Therapy (Seite 144)

[Cyberhexe]

...und wieso Fake News?
Die Fakten, bspw. dass Mineralöl bei den Plazebos verwendet wurde, ist doch keine Fake. Und wenn ein Kardiologe (Ethan Weiss) äussert, dass ihn dies irritiert, dann entspricht dies wohl auch der Wahrheit.

Ich weiss nicht, weshalb diese Nachricht dich veranlasst, unter die Decke zu hüpfen?

Obschon kurzfristig immer eine Reaktion auf solche Nachrichten möglich ist, wird die mittelfristige Kursentwicklung dadurch sehr wahrscheinlich nicht beeinflusst.

Deswegen ... Keep Cool!

[Magnetfeldfredy]

https://investor.amarincorp.com/static-files/2e95e517-3545-4…

Das ist der Beweis für die Fake news, armes Amerika, da haben Sie eine Waffe gegen Herzinfarkt, Schlaganfall, Tod....so gut wie ohne Nebenwirkungen und Dreckskapitalisten ala Feuerstein, Herpes von Forbes

[Magnetfeldfredy]

Das Placebo war von Anfang an bekannt und als leichtes Mineralöl deklariert und von der FDA akzeptiert, der letzte Versuch der shorts die phantastischen Daten kleinzureden!
Die Konkurrenz wird alles versuchen die bahnbrechenden Ergebnisse mit dem Mineralöl-Fake kleinzureden, wird nicht gelingen!

[Cyberhexe]

In einer Pressemitteilung von gestern hat Amarin die neusten Erkenntnisse zu VASCEPA veröffentlicht und auf einen kontrovers zu diskutierenden Umstand hingewiesen:

https://investor.amarincorp.com/news-releases/news-release-d…

Landmark Cardiovascular Risk Reduction Benefits Demonstrated in REDUCE-IT Are Largest of Any Major Cardiovascular Outcomes Study of a Drug Intended to Address Residual Cardiovascular Risk Remaining After Cholesterol Management

Cardiovascular Death Reduced by 20%
Fatal or Nonfatal Heart Attacks Reduced by 31%
Fatal or Nonfatal Stroke Reduced by 28%
Urgent or Emergent Coronary RevascularizationReduced by 35%
Hospitalization for Unstable AnginaReduced by 32%
Number Needed to Treat for Primary Composite Endpoint: 21
Patient Years of Study Support Favorable Benefit/Risk Profile in REDUCE-IT
Affordably Priced Vascepa Positions Amarin with Potential to Help Millions of Patients

Anbei eine Zusammenfassung der wichtigen Punkte (AUF DEUTSCH!):

-Detaillierte Ergebnisse der Studie --> REDUCE-IT, zeigen, dass Vascepa das Risiko für Tod, Herzinfarkt und Schlaganfall um 26 Prozent reduziert

- die Daten, so Deepak Bhatt, Kardiologe am Brigham and Women's Hospital in Boston und Studienleioter der REDUCE-IT-Studie, seien "extrem stark" ... "Diese Daten haben das Potenzial, ein Paradigmenwechsel zu sein, genau wie vor Jahrzehnten, als die Statine zum ersten Mal auf den Markt kamen", fügte Bhatt hinzu. "Als Akademiker versuche ich, einen gemessenen Ton zu halten, aber es ist schwer, die Begeisterung über diese Ergebnisse einzudämmen."

- die Ergebnisse wurden von Bhatt am Samstag auf einem medizinischen Treffen der "American Heart Association" in Chicago präsentiert und werden ebenfalls im NEJM ( New England Journal of Medicine ) veröffentlicht

- es gibt anscheinend eine Unstimmigkeit in den vorgelegten Daten, dessen Aufarbeitung auf Montag angekündigt ist --> die Daten der VASCEPA-Studie enthalten ein verwirrendes * (Asterisk), welches darauf hindeutet, dass den Placebo-Kandidaten der Studie eine mit Mineralöl gefüllte gleich aussehende Pille appliziert wurde. Diese könnte im Kontrollarm verstärkt Herzprobleme verursacht haben.
Dr. Ethan Weiss, Kardiologe an der University of California, San Francisco, Medical Center wird hierzu folgendermassen zitiert: "Ich kann mir einreden, dass diese Frage keine große Sache ist, aber sie ist da und das macht die Daten unordentlich und ein wenig enttäuschend."


Bin gespannt, welche Auswirkungen diese Diskussion am Montag auf den Aktienkurs haben wird. Sicherlich wird es etwas abwärts gehen.

[Magnetfeldfredy]

What is Amarin’s perspective on the use of mineral oil in its clinical trials?
All information below has been previously disclosed
other than Figure
s A and B
.
A placebo comprised of light liquid paraffin oil, or mineral oil, was used in the MARINE, ANCHOR and
REDUCE-
IT clinical trials
of Vascepa. Mineral oil was selected as the appropriate placebo to mimic the
color and consistency of Vascepa.
No strong evidenc
e for biological activity of mineral oil was
identified
•
in connection with FDA
approval of Vascepa
in July 2012 based on the MARINE phase 3 clinical
trial,
•
in connection with FDA review of the ANCHOR phase 3 clinical trial or
•
after several years of quarterly review by the Data Monitoring Committee, or DMC, for REDUCE
-
IT cardiovascular outcomes trial after FDA requested the DMC to periodically review unblinded
lipid data to monitor for signals that the placebo might not be inert.
Each of the three Vascep
a clinical trials
, MARINE, ANCHOR and REDUCE-
IT,
was conducted under a
special protocol, or SPA, agreement with FDA in which mineral oil was agreed
with FDA as an acceptable
placebo. A SPA is an evaluation by the FDA of a protocol with the goal of reaching
an agreement that the
trial protocol design, clinical endpoints, and statistical analyses are acceptable to support regulatory
approval of the drug product candidate with respect to effectiveness for the indication studied.
MARINE
FDA approval
of Vascepa
in 2012 was based primarily on
efficacy data from the MARINE trial. As part of
this approval, Amarin submitted
to FDA data from both
the
MARINE
and ANCHOR trials
for consistency
of results and review of safety data. C
onsideration of external
data regardin
g characteristics of mineral
oil
was also assessed by FDA before FDA’s approval.
ANCHOR
During the October 16, 2013 public advisory committee meeting held by FDA as part of its review of our
ANCHOR sNDA, a discussion was held regarding observed, nominall
y statistically significant changes in
the placebo group from baseline of certain lipid parameters in an adverse direction, while on
background statin therapy. Nevertheless, the discussion raised questions about the possibility that the
mineral oil placebo
in the ANCHOR trial (and then at use in the REDUCE
-IT trial) might not be biologically
inert and might be viewed as artificially exaggerating the clinical effect of Vascepa when measured
against placebo in the ANCHOR trial. It was ultimately concluded that the between
-group differences
likely provided the most appropriate descriptions of the treatment effect of Vascepa and that whatever
factor(s) led to the within
-group changes over time in the placebo group were likely rando
mly
distributed to all treatment groups.
From May 2015 through March 2016, in connection with the First Amendment litigation with FDA and
the related settlement agreement that allowed us to promote the results of the ANCHOR study, FDA did
not dispute the
veracity of the ANCHOR trial data
or
seek to require that we include any qualification in
our promotion of ANCHOR data related to the mineral oil placebo.
REDUCE
-IT
Early on in the course of the REDUCE
-IT trial, FDA
directed the D
MC
for REDUCE
-IT to perio
dically review
unblinded lipid data to monitor for signals that the placebo might not be inert. After each such quarterly
unblinded safety analysis and review meeting, the DMC recommended to continue the REDUCE
-IT study
as planned. Each of these DMC recomm
endations was shared with FDA.
In August 2016, we announced an amendment to our REDUCE
-IT SPA agreement with FDA that
reaffirmed FDA concurrence on key elements of the study
. In this amended REDUCE
-IT SPA agreement,
FDA agreed that, based on the informati
on submitted to the agency, the critical elements of the revised
REDUCE-
IT protocol and analysis plans adequately address the objectives necessary to support a
regulatory submission.
As published within the main presentation of the REDUCE
-IT results (Bhatt
DL, Steg PG, Miller M, et al. N
Engl J Med. 2018.), at baseline, the median LDL
-C was 75.0 mg/dL. The median change in LDL
-C was 3.1%
(+2.0 mg/dL) for VASCEPA and 10.2% (+7.0 mg/dL) for the mineral oil placebo arm; placebo
-corrected
median change from bas
eline of -
6.6% (
-5.0 mg/dL
; p < 0.001). If mineral oil in the placebo might have
affected statin absorption in some patients, this might have contributed to differences in outcomes
between the groups. However, the relatively small differences in LDL
-C leve
ls between groups would not
be likely to explain the 25% risk reduction observed with VASCEPA, and a
post hoc
analysis suggested a
similar lower risk regardless of whether there was an increase in LDL
-C level among the patients in the
placebo group.
See
Figure
s A and B
.
Figure
s A and B
Although open label, Japan EPA Lipid Intervention Study (JELIS) previously demonstrated a 19% risk
reduction without a mineral oil placebo.
Summary
The use of mineral oil placebo in REDUCE
-IT cannot
explain
the
significant 25% risk reduction in the
study
, even if one assum
es the placebo was not fully inert
. The independent Data Monitoring
Committee
review throughout the almost seven
-year study
and reviewers at
The New England Journal
of Medicine
, after careful
review
of relevant data,
concluded
that the results of the REDUCE
-IT study
reflect that VASCEPA significantly lowered the risk of ischemic events, including cardiovascular death
.
Amarin stands behind these results as presented at The American Heart Associ
ation and published in
NEJM.
Amarin looks forward to the results of this landmark study being used to help many at
-risk patients

[Magnetfeldfredy]

Wie geil, nochmals die unglaublichen Ergebnisse:


Nov 10, 2018

Landmark Cardiovascular Risk Reduction Benefits Demonstrated in REDUCE-IT Are Largest of Any Major Cardiovascular Outcomes Study of a Drug Intended to Address Residual Cardiovascular Risk Remaining After Cholesterol Management

Cardiovascular Death Reduced by 20%
Fatal or Nonfatal Heart Attacks Reduced by 31%
Fatal or Nonfatal Stroke Reduced by 28%
Urgent or Emergent Coronary RevascularizationReduced by 35%
Hospitalization for Unstable AnginaReduced by 32%

Number Needed to Treat for Primary Composite Endpoint: 21

Patient Years of Study Support Favorable Benefit/Risk Profile in REDUCE-IT

Affordably Priced Vascepa Positions Amarin with Potential to Help Millions of Patients

Conference Call Scheduled for Today, Saturday, November 10, 2018 at 7:15 pm CT/8:15 pm ET

[Magnetfeldfredy]

https://www.nbcnews.com/health/heart-health/drug-fish-oil-cu…

[Magnetfeldfredy]

https://www.youtube.com/watch?v=6NsUfLAy0DM

[Magnetfeldfredy]

wso_0_407a69c1ad01bbd48e76f9b83fc45bf5

[Magnetfeldfredy]

Jefferies: Amarin Corporation (AMRN): Strong CV Data at AHA at High-End of Expectations - Minor Debate Expected - BUY


Amarin Corporation (AMRN): Strong CV Data at AHA at High-End of Expectations - Minor Debate Expected - BUY


Rating BUY

Price Target $30.00

Price $21.05

Bloomberg NASDAQ: AMRN

*General: Estimated fully diluted sharecount includes all stock options, RSUs and preferred stock

*General: Pro Forma debt value assumes that the $30M of senior notes were exchanged (per AMRN's Oct 19th announcement)

Key Takeaway

The long-awaited REDUCE-IT was presented at AHA with new robust 26% benefit on key MACE-3 endpoint (in context much higher than PCSK9) and 20% benefit on CV mortality with a strong safety. The presentation was met w/ applause and well received by the audience when MACE data went up w/ extreme statistics of p<0.0000007...minor debate as expected on placebo will likely go on but results are strong nonetheless...**EMAIL us for SLIDES and related VITAL study**

Overall near best case scenario on efficacy and safety: In the landmark REDUCE-IT study, Vascepa showed stat sig on (1) an overall 25% reduction of MACE CV events w/ p=0.00000001, and importantly, new info including (2) 26% reduction in MACE-3 (death, MI, stroke) which are the most important CV events at w/ p=0.0000006, (3) significant 20%-35% reduction across all other major pre-specified hierarchical testing endpoints including CV death (20% benefit), hospitalization (32%), MI (31%), and stroke (28%). On all-cause mortality there was a trend at 13% at p=0.09 but driven by no difference in death outside of CV events which would be expected since the drug is treating CV events.

Notable survey at AHA session somewhat summed this up: At the end of the AHA session which presented the VITAL study (a failed generic fish oil study at low 1g dose showing minor trends) and then showed the REDUCE-IT study (high dose 4g pure EPA) an interactive survey was presented to attendees that perhaps summed up the general feedback. As a result of this session: 11% would prescribe any triglyceride lowering agent to all high-risk pts, 2% would prescribe any fish-oil prep to high risk pts, and 87% noted they would prescribe exclusively EPA 4mg daily in all high risk pts with moderate TGs. These two presentations and prior historical data may suggest that AMRN's high dose 4g of pure EPA has significant benefit beyond low dose 1g non-pure EPA mixtures and other drugs. This is an important point that KOLs have suggested is a key difference and that is notable vs other failed studies.

Yes there will be some debate on whether placebo is helping the drug effect but it's not likely to drive the overall view 4g EPA is beneficial. In the study and consistent w/ an old debate around use of mineral oil in placebo (to look like active drug), the placebo had changes early on but moderated by the end. Per comments from the lead presenter - he noted importantly when the data is cut by whether LDL goes up or down in control group - the Vascepa magnitude of benefit is the same so change in LDL in placebo doesn't matter (and suggested various public comments in other media outlets by docs may have an agenda or bias). Of note in the results (1) placebo had a modest TG increase of +2%-3% at Year 1 but still ended -7% at last visit vs Vascepa -19-22% and in line, (2) LDL-c for placebo was +9%-11% first year and +7% at end vs. Vascepa minor -1-2% changes through the study. Of note - we have a "comparator" chart (email us) showing all major recent CV/TG studies showing LDL does increase in pbo in most studies including PCSK9 by 2%-9% even within a few months and markers such as hsCRP went up +30% in placebo p<0.01 while Vascepa hsCRP went down 13%-14%.

Bear feedback: Placebo impact on lipid parameters and inflammation markers may have confounded results and add question to validity or magnitude of effect; results could be viewed disappointing relative to high expectations; M&A is not a likely scenario given valuation, capital/balance sheet requirements. Bull feedback: Data is home run and results were high end on all major CV parameters; mineral oil question is fake news and old news and cannot drive a gigantic benefit to say that is causing so much harm; value proposition for $3B-$8B drug is very attractive to big pharma.

Michael J. Yee *, Equity Analyst



* Jefferies LLC / Jefferies Research Services, LLC