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HDGabor: I never said it was rational. On the
contrary. It was a huge blunder.
mrmainstreet: I'd much prefer to talk NFL
football and what a great talent R Wilson
is. They should be able to run against
the Pack. Good luck !
sts66: guidelines which show Trigs are associated
with Cariovascular risk and hopefully approve the
Anchor indication. This is just my trying to be
positive. The recent publications also give FDA
cover to reinstate the SPA, and saving face is
is FDA's mantra. This is just a guess, as I have
no knowledge what their thinking is.
sts66: I hope so, though I have no idea. Optimist
that I am, the FDA can now state recent publications
showing elevated Trigs to be a risk factor, quote
The E
alternate: In all due fairness all FDA wanted
was to revise the SPA. This is not opinion or
conjecture. This was predicated on tying the
Anchor approval to Red-it results. This would
allow the Co to sell Vascepa for Trigs between
199-499mg/dl, but not allowing them to market it
other than lowering Trigs. There would be a Boxed
warning that Vascepa has not been shown as reducing
CVE. Straight forward, and essentially a partial
win for FDA, without deviating from AHA/ACC guidelines.
JL : Giving you the benefit of the doubt I assume
your IQ is north of 50. Aren't you the same guy who pushed
for No Sales Reps, GIA , and supportive of Mgmt. What is
it you don't understand about Thero believing he was in
a negotiating process with FDA, not being fluent in FDA
speak, and without prior FDA experience, it never dawned on
him how FDA dialogue works. They are known to pull the plug
on a Friday after the other side continues to stick to a
original position. Anchor or nothing. He wound up with nothing. His own CMO tried to get him to agree to a compromise, but he stood firm. AMRN will never admit to this and I hear the CMO will be let go. This is not just my opinion. Perhaps, considering your stock losses on AMRN, you ought to try finding new sources that are reliable.
THIS IS NOT CONJECTURE !
ladavis23: It should read "Incompetent Egomaniacs"
Kiwi: You are absolutely correct. I was really
referring to Jupiter, done and data mined by
AZN. PROVE-IT was done about 10 years ago. My
recall was late 90's. See what happens when
you get older.
Ziploc: What you state makes a lot of sense but the
timing is questionable. If FDA knew they were not
going to approve Biomarker results, they would have
been obliged to let AMRN know long before Adcom. The
PCSK9's are using reduction od LDL as a primary endpoint.
AMGN,PFE, REGN, SNY. They have agreed to do PH IV Outcome
Trials, but as agreed with FDA, only following approval.
BioChica: Not to worry, there's only been one
high dose Statin study that showed positive
results since the 90's. That said, the trial
was done by AZN using Crestor,(2006) and not
sanctioned by FDA, or reviewed by FDA. People
have been somewhat suspect of the results, because
it's never been replicated.
Freak: The fat lady hasn't sung yet !!!!
HD: Thank you for your thoughts ! I must say we're
on the same page, though the time schedule is very
different. The bottom line of clinical trials that
those that are event driven,usually take longer
than everyone thinks. Time is not our ally. I am
discouraged by the 5000 enrolled patients you state with
low LDL's. That raises the bogey for efficacy to be shown
with the Power and Hazard Ratio. Lets assume we do well
and get 18% efficacy, that's the kind of number we need.
The only thing we need is a compelling P value that shows
unequivocal efficacy.
HDGabor: Questions ? I wonder whether you share my concern
about an early interim look of Red-it by DSMB ? My issues
are as follows.
1- The first 2000 patients were enrolled with Trigs around
150mg/dl, and then moved up to over 200mg/dl.
2- The Power and Hazard ratio are such that all of the
8000 patients need to on board. I'm not sure this is the
case, either because AMRN is cash strapped, or has not fully
enrolled to give them leverage against FDA re completion of
the trial. I assume FDA wants a final answer to whether lowering
Trigs lowers the incidence of CVD.
3- By a back of the envelope calculation I personally doubt
whether there will be results before late 2018 or possibly
early 2019. Do you concur ?
Thanks
BioChicaL•
"Notwithstanding the preceding, the issue should have been a non-issue, as it was identified by Dr. Iffat Chowdhury of the FDA in her review of the earlier MARINE trial (with identical protocols). She concluded that the data submitted supported the assertion that light mineral oil does not increase serum TG levels. She also noted in her review notes that “similar increases in TG levels were observed in the placebo groups from the Lovaza clinical trials of hypertriglyceridemic patients.”
sts66: I believe if you go back and check
the Marine placebo, you'll find it was
mineral oil.
JL: My take of the PCSK9 drugs is analogous to
Vascepa's getting the Marine approval first. For
Trgs over 500mg/dl. I believe the PCSK9 went after
HF first and will do the necessary trials so as to
file sNDA's for plain old Hypercholesterolemia. They
certainly lower LDL substantially. If it were just
for FH, I doubt PFE,AMGN, SNY, REGN would all be chasing
a $1B market opportunity. I'd like to hear your thoughts
Kiwi: Check out the PCSK9 results I posted.
Hopefully they maybe a G-d send for you.
The CEPT article I sent you was the wrong
article. I meant to send you the PCSK9
data set,
dmicento: These are most likely sealed, and came
about as private discussions between FDA and the
Congressman. Suffice it to say, I know that the
info is both accurate and true. I apologize for
this vague answer, but I'm unable to say any
more. Some wont like this response, but confidentiality
trumps all else.
ladavis23: I honestly don't have a clue. The
results of the PCSK9s and CEPT Inhibitors are
both LDL lowering agents , and have stolen the
headlines this past week. Since they fit the
new ACA/AHA guidelines, the FDA if they continue
to give AMRN short shrift, can find cover in the
new guidelines. I am hoping that with all the mistakes
made by both sides, and FDA's style of saving face,
a win, win for both sides would be the compromise
as you suggest.
JL: I also believe that the CEPT Inhibitors
will eventually replace the PCSK9s. What is
your thought. Dezima, curiously of Dublin
is in the lead with CEPT Inhibitors
JL: The FDA vetted mineral oil during the Marine
approval process. Their own expert Dr Iffat Chowdhury
identified the Mineral Oil issue during the Marine
review, and concluded that it was an acceptable placebo,
and further referenced that there were also small elevations
of Trgs in the Lovaza placebo approval as well. If the FDA
accepted mineral oil in both the Lovaza and Marine trial,
and then recommended it's use in the Anchor indication; I
have a big problem with their penalizing AMRN for its
usage. Btw, as you must recall, this was Cong Waxman's
main point in his meetings with FDA and the result was
FDA putting Anchor back on the table. Taking this at face
value is my best guess as to the up coming decision. As
you know, FDA, can literally change their minds on a whim,
but I believe that legally, this is their achilles heel.
JMO.
JL: As our resident Lipidologist, do you believe
that the AHA/ACC change in guidelines has anything
to do with these new agents ? They show a lowering
in CVD of 54% "large study' having any effect on
Red-it hitting a lowering of CVD of say 20% ? I'm
really uncertain of what to make of this. I do believe
you're right about Statins. Non compliance was huge.
Thanks
FYI cognitive Disorders:
Doctors see CV risk reduction encouraging. 54% relative reduction in CV risk was seen in LONG- TERM trial
They see LDL goal achievement at low dose very encouraging
Do not see any major issues with the safety of Alirocumab
The neurocognitive disorder events were small and similar in both treatment and control groups
Detailed Data
#1 Odessey combo- 51% ldl reduction at wk 24 and 50% at week 52
77% achieved ldl goal of below 70
Patients were evaluated at wk 8 to decide to dose up to 150mg. 80% pts did not need higher dose
Treat to target trial design
Mean achieved ldl was 53 at week 24
We need novel drugs for statin intol, HeFH and high risk patients. Also lower LdL is better.
4 neurocognitive disorders in treatment arm and 3 in the control arm- similar in both trials
Most SAE were injection site reactions with PsCK9
Self administered alirocumab had good compliance
#2 FH-1 and FH-2 trial
Same treat to target design at wk 8
Younger population -
Baseline Mean ldl 145 in FH-1 135 in FH-2
49% ldl reduction
Only 50% patients had dose increase
71% in FH1
Neurocognitive disorders 1 in alirocumab 3 in control.
Major events higher in alirocumab arm were Injection reactions and common cold.
Fh1 more 70% were diagnosed clinically but in FH2 more 80% were diagnosed genotypically. Results were same for both trials
Absolute reduction is 2mmol/dL
Cv events 6 in treatment arm vs 3 in treatment arm. Numbers are very small however
#3LONG- TERM trial
Combines patients with HeFH and high risks
Patients got 150mg or placebo
Baseline ldl 122 mg/dL
61 % reduction at week 24.
79% achieved ldl goal of less than 70 at wk 24
Neurocognitive disorders balanced at 4% in both arms
Major difference was in injection site reactions
54% relative risk reduction in Cv risk when plotted on KM curve
Chd death 0.2% vs 0.8% control
Penalist comments
Great news for patients. Regulators will have tough job after these strong data
Only caution is anything less than 100 events should be seen as encouraging but with caution
Lpa also was reduced significantly. Not many drugs do that
BioBill: The statin you're looking for is
Livalo, which has the highest compliance
rate of all statins. I switched from Lipitor
to Livalo almost 3 years ago, and all my
musclo-skeletal symptoms vanished one week
after discontinuing Lipitor. Btw, Kowa has the
rights to Livalo as well as Vascepa. Somebody
at AMRN or Kowa should pay attention.
BioBill: The PCSK8s are the future. As far as
the "Cognitive Disorders" mentioned on this site,
the incidence showed no difference from control
groups, and in one study just released from the
Barcelona meetings, showed no difference from
placebo group. I only wish that applied to the
mineral oil issue.
sts66: Excellent post. Extremely well written.
One caveat. Considering the myriad functions
of FDA, including Meat an Poultry inspections,
Bio/Pharma manufacturing inspections, reviewing
new drug applications, and all the budgetary
short falls, they need restructuring from within,
not a complete overhaul, starting from scratch.
I believe Waxman's 1997 signature legislation,
(Hatch Waxman) has leveled the playing field
and that trend continues. If not for AMRN, none
of us would be upset with FDA. Considering other
Govt Agencies, IRS, NSA, CIA etc, FDA IMO, is
doing a reasonable job. The only thing we have
to acknowledge is that all Govt Agencies, here
and abroad, particularly the sacrosanct Oval Office,
are all corrupt and inept. That is the only given
in a world run amok.
FYI Presentation From Barcelona Meetings:
9-01-14
New guidelines expand the scope of statin therapies
The theme of all the presentations was that even with all the treatment options available there exists a substantial proportion of patients who do not reach LDL goal of 70.
An analysis of patients coming with ACS indicates 31.4% pts with ACS had no indication of primary prevention. If they would have gone one day prior to the ACS event.
A vast majority of patients 80-90% that should have been on statins were not on that.
In another study of 1000 pts, only half of the patients get to the goal of reducing 50% ldl with high intensity statins plus zetia. Statin plus zetia gets 43% pts to goal lower than 70 vs statin alone 35%
Doctors believe that they need to have LDL target. The goal of 70 is difficult to achieve. Still this should be the goal.
Meta-analysis- to what extent high intensity statins reduce ldl- analysis of 32k patients from clinical trials- overall reduction in LDL levels was approximately 45-55% in overall population.
1/3 patient is still not on target.
Another study in high risk patients looking at patients achieving the goal- DYSIS study 68K patients - 26K were at very high risk- most were on moderate statins (72%). Only 21% were below goal of less than 70. Mean ldl was 100.6 even after statin treatment. In patients not at goal, they were 34mg away from target.
Compliance is an issue with statins. After 5 years compliance went down to 60% in pts with documented coronary artery disease.
Common question was - is ldl goal of 70 un-achievable in patients with high risk.
DYSiS study- addition of Zetia or increase in statin dose - reminder with statins alone 21% reached ldl goal of below 70 mg/dL. The model suggests 1) use of higher dose statins you would get to 27-33% 2) add zetia w/o changing statin dose we would get 45% to goal. Highest dose statin plus zetia will get 60% patients to goal of 70 m
jpsebasti: Interesting thought, though tossed around
for a couple of years. What makes it more intriguing
is that AZN, despite all the noise on this site, is
preparing for a 2ND major bid from PFE. Pfizer's
first priority is to reinvent itself, lower it's
tax rate through inversion, and pick up a pipeline.
PFE would IMO, be more amenable to pick up AMRN,
as their loss of Lipitor revenues could be easily
restored, albeit not at the $17B/yr, by marketing
Crestor and Vascepa for Mixed Dyslipidemia. They
could also ramp up Red-it, and get earlier results
and approval,by a cash strapped AMTN.
FYI
Dezima CETP inhibitor meets endpoint in dyslipidemia trial
Dezima Pharma B.V. (Naarden, the Netherlands) said TA-8995 (DEZ-001) alone or in combination with statin therapy met the primary endpoint vs. placebo in the 364-patient Phase IIb TULIP trial to treat dyslipidemia. The primary endpoint was a composite of the change from baseline in LDL-C and HDL-C at week 12.
Dezima plans to publish full data in the coming months and start a Phase III trial next year. The company has exclusive, worldwide rights, excluding certain Asian territories, to the cholesteryl ester transfer protein (CETP) inhibitor from Mitsubishi Tanabe Pharma Corp. (Tokyo:4508) (see BioCentury, Jan. 28, 2013).
Two other CETP inhibitors are already in Phase III trials: anacetrapib (MK-0859) from Merck & Co. Inc. (NYSE:MRK) and evacetrapib (LY2484595) from Eli Lilly and Co. (NYSE:LLY
hamky: It may seem o you a weak theory; however,
it is fact and not theory. Happens all the time
when there is the potential for a directional move.
When these funds were seriously involves, they owned
M's of shares ( SAC owned over 5M ). 384,000 is in
fact a speculative move. At least for myself and a
few other PM's I've spoken to.
ladavis23: I hope you're wrong as well.
That said. the most important fact that
the Board is missing is the rational of
share purchases by Funds, SAC etc. Funds
look at the share price and for them it
is really like buying Calls with no time
erosion. If the funds would be purchasing
Millions of shares , that would be of greater
significance. Buying 384,000 shares is chump
change to large funds. They are in essence buying
call options with no erosion related to time.
This is purely a speculative play, and I have
also bought shares, for the very same reason.
In a worst case scenario , the downside is
quite limited.
BioBill, BioChica: BB, thank you for your kind words
and appreciation. I want to also thank you for pointing
out my inappropriate note to BioChica. I am publically
apologizing for my lack of cool. I come to the Board
about once every month or so in an attempt to try and
fill in some of the blanks. I was beyond annoyed at
getting poked in the eye with a stick to prove or reveal
my sources, in a sense being asked to verify my comments.
Again, my apologies.
Invest83838: Fair enough. My meeting with Waxman
came about after ADCOM. The purpose was to help
him see the bogus science rational for voting down
ANCHOR. Since Waxman's signature legislation was
the 1997 Hatch/Waxman Bill, in essence creating
"The SPA" to level the playing field between Small
Cap Biotech and Large PHRMA, as well as establishing
exclusivity periods,(NCE, NME) he was obviously the man
to speak to. Yes he is retiring, and No , I never worked
with him or for him. Coincidentally I am a constituent
of his, living in Beverly Hills, and have financially
supported his Political efforts in Congress for many,
many years, I knew him personally and was able to
get right through to him. I know that following our
meetings he went directly to FDA and that's how the
SPA was put back on the table. I also enlisted the
aid of Senator Chuck Grassley who was of enormous help
to Waxman and AMRN. Had we had a real Mgmt Team, all of
this could have been avoided. Thank you for your interest
and persistence.
HDGabor: You seem like a well informed , bright
guy. What is so difficult about respecting what
I deem as a confidential source that is business
related. I would never breech a confidentiality.
Suffice it to say that that FDA requested ( Public
information)a significant revision of the SPA .
Obviously by the result, AMRN must not have agreed.
BioChica: Let go of the Bull Shit.
I am usually forth coming except
when it violates a confidentiality.
Besides your inane posts contribute
absolutely nothing to this site.
Back off !!!
ggwpg: It does seem logical, but the FDA
has never been accused of being logical.
I can't comment on your 2nd question
Quote
From FDA Minutes
'Notwithstanding the preceding, the issue should have been a non-issue, as it was identified by Dr. Iffat Chowdhury of the FDA in her review of the earlier MARINE trial (with identical protocols). She concluded that the data submitted supported the assertion that light mineral oil does not increase serum TG levels. She also noted in her review notes that “similar increases in TG levels were observed in the placebo groups from the Lovaza clinical trials of hypertriglyceridemic patients.”
stanglish: The exact statement (Quote) from the
FDA minutes of the meeting. They gave FDA's expert
witness Dr Iffat Chowdury's testimony word for word
Mineral Oil : One major point about mineral oil
that has not been brought up a very long time is
that with both the Marine and Anchor protocols,
FDA Twice blessed Mineral Oil as the comparator.
This was a major point in my discussion, presentation
to Congressman Waxman. The FDA called in their own
Mineral Oil expert Dr Iffat Chowdury. She testified
to FDA that Mineral Oil has no effects on Trigs,
and other Lipid metrics. If memory serves me, the FDA
made a statement that Mineral Oil was the Comparator
for both Marine, and subsequently Anchor Clinical
Protocols. I stressed to Waxman that how can Sponsor
or Comparator be questioned about this issue when Agency's
own expert stated it had no interaction with Lipids.
Their argument and the proof that I supplied to Waxman,
was one of several catalysts that got Waxman involved
in behalf, of Amarin, and had FDA put the SPA back on
the table. He had never been of the opinion that a SPA
could be rescinded, specifically for following FDA guidelines.
Having been a CEO in Biotech I can honestly
tell you that you are wrong. A CEO gets paid
for execution. He works the BOD, rides shotgun
of the CMO or CSO, and basically makes every
important decision pertaining to executing the
mission statement. NoFan is spot on ! One of the
few on this site. No Senior Mgmt Team has ever
had a more dismal track record on execution as
JT, and team. They were put together for the sole
purpose of JZ selling the Co after the Marine
approval. He BS'd The Street, publically stated
"THAT HE HAD MORE OFFERS THAN EMPLOYEES" . He
drove the stock up to $19 and promptly sold $M
of his own stock. He never had an offer, Thero
told me that personally. He poisoned the FDA well,
and was a no show at the ADCOM meeting because he
was persona non grata. JT was along for the ride
and found himself CEO without any management experience,
and executed the irrational decision of GIA. Then
he stuck to his guns, stating it was Anchor SPA
or nothing on the Friday before MLK weekend. FDA
pulled his plug the following Business day. Kiwi
I didn't even mention his again selling millions
of dollars of his stock into the Marine approval.
That is a first on Wall Street, a Biotech CEO selling
his stock into his first FDA drug approval. Give me
a break if you just think a CEO is a cheer leader !
That is PLAIN AND SIMPLE wrong headed.