OT...NASH failure by NGM
_______________________________________________________________________


May 24, 2021 07:00 AM EDTUpdated 07:59 AM R&D
NGM concedes key failure for their lead NASH drug, closing the door on a pivotal followup — and asking analysts to look past the wreckage into the pipeline


John Carroll
Editor & Founder
Amber Tong
Senior Editor


A little more than a year ago NGM whipped up considerable enthusiasm for its anti-fibrotic NASH drug aldafermin based on a cohort of patients who showed a marked response to the treatment. But its great expectations — backed by some enthusiastic analysts — failed to pan out at the primary endpoint in the crucial Phase IIb that followed among people with with stage 2 or 3 fibrosis. And while another trial in more severely afflicted patients is continuing, NGM is taking its $400 million in cash reserves and shifting focus to the rest of the pipeline, ending any hopes for a pivotal in this group — and blasting the beliefs they had inspired earlier.

NGM CEO David Woodhouse isn’t applying any spin on the data. The primary — an improvement in fibrosis with no worsening of NASH among the 107 patients taking a 0.3 mg, 1 mg or 3 mg dose — flopped badly, with a p-value of 0.55. The 1 mg dose fell behind the placebo as well as the 0.3 group, while undercutting expectations of efficacy overall. There was a significant improvement in NASH resolution (at the 3 mg dose) and “multiple non-invasive measures of NASH,” including liver fat content reduction, reductions in the liver enzymes ALT and AST; and-reductions in Pro-C3, a biomarker of fibrogenesis.

But that wasn’t good enough to stake a Phase III pivotal roll of the dice on.

“It is disappointing for not only us but for patients too,” Woodhouse told me in a late-night preview of the readout this morning. “There’s a big unmet need with nothing available for treatment. What we see here is that there continues to be activity and consistency around many of the things we measure around NASH. This key endpoint, that seems to be quite a variable endpoint.” It’s early days for NGM with the data, he added, and this was a well conducted trial, but: “It does seem like this variability around this endpoint didn’t work in our favor.”

NASH is an incredibly complicated disease, he adds, involving patients with a host of problems. “This is a really difficult disease to measure progression and reverse of; there’s a frustration being beholden to the biopsy,” says Woodhouse, when a combination of noninvasive measures could be used — but need to be validated.

Looking at the percentage of patients who saw their fibrosis improve by at least 1 stage without worsening of NASH, the biotech reported 31% and 30% response rates for the 0.3 mg and 3 mg groups, respectively. But among the middle, 1 mg dose cohort, only 15% reached that threshold — an even smaller percentage than placebo (19%). The four groups each had similar numbers of patients.

The data look similarly messy across secondary endpoints. The key figure that carried statistical significance involved the observation that 22% of patients who received aldafermin 3mg achieved NASH resolution with no worsening of fibrosis. None of the doses spurred both fibrosis improvement and NASH resolution in a large enough number of patients.

In addition to biopsies, investigators also reviewed biomarkers measured by non-invasive means, and noted a reduction in liver fat at the 1mg and 3mg doses.

Analysts had painted this one as a key catalyst for the stock $NGM, making this a painful morning for the biotech. Its shares plummeted 51% ahead of the bell on Monday. That’s a wipeout of more than $1 billion in market cap.

While investors and analysts have been zeroing in on NGM’s NASH program, though, the company has been steadily building a pipeline with new drugs aimed at cancer and ophthalmology — arenas where they hope to do better.

That pipeline includes several drugs now in human trials. One of the top drugs in that category is NGM120, a cancer therapy that is being tested for pancreatic cancer and cachexia — a wasting disease that afflicts patients.

NGM707, meanwhile, blocks 2 receptors in the tumor microenvironment, looking to improve immune responses by inhibiting both the ILT2 and ILT4 receptors. And there’s a drug called NGM621 that blocks complement C3, targeting geographic atrophy with a potential dosing regimen of every 8 weeks.

NASH drugs in general have been under a considerable cloud. The field, which kept collecting sizable venture checks betting on a comeback after repeated disappointments, saw the two leading biotech efforts implode up close, with Genfit failing a closely-watched Phase III and Intercept getting unexpectedly slapped down at the FDA after submitting positive results on one of two primary endpoints (notably, Intercept’s drug did help patients improve fibrosis, making it the lone winner in the late-stage race). Both, like NGM, signaled that they will be getting out of NASH altogether — even as earlier-stage players carry on with their pipeline while bigger ones like Gilead and Novo Nordisk team up to try a combo approach following stinging setbacks.

NGM had sold their 2019 IPO on the notion that the anti-fibrotic NASH drug — formerly NGM282, a take on human hormone FGF19, which researchers had explored for its ability to diminish liver fat content and quell bile acid — could be a game-changer in the field.

One good thing the execs can say about it now is that it looks safe: Only 2% of patients in each of the three arms dropped out of the trial because of a treatment-released adverse event, compared to 5% for placebo. While one patient died in the 1mg arm 30 days after the last aldafermin dose, the site investigator concluded it was unrelated to the therapy.


Cheers!
Flubber

@ meowza...IP rights and COVID vaccines...

https://www.bloomberg.com/news/articles/2021-05-05/u-s-to-back-waiver-of-vaccine-ip-protections-at-wto-tai-says?srnd=premium&sref=i4qXzk6d


and Mr. Spock's classic line in StarTrek, The Wrath of Khan...

@ raf...

Not sure about scrips. COVID has obviously affected visits to physicians. This morning I read an article about an increase in cancer diagnoses due to the fact that many individuals afraid of COVID, had cancelled their normal cancer screening tests....mammograms, etc.

Share price? With a positive ruling by Du, I feel we would at least be in the $20s. Just a guess, but what do I know? I thought we would have been bought out 2 years ago in the upper $30s or low $40s.

It's all a blur now!


Cheers!
Flubber

@ Invest83838...unfortunately I think you are correct. AMRN will never get a monkey off of its back. It's always one thing or another.

AMRN is always fighting against something....

Complete Response Letter
AdCom
Mineral Oil
Insurance denials
'fish oil'
Generic patent infringement
Adverse patent ruling
Appeals denied
Anti-trust lawsuit


WHEN DOES IT END???

The days of hoping for a stock price of $30+ are long gone in the rear-view mirror.


Cheers!
from a weary Flubber

@ ralphey....a little late today to respond to your comment, but since day #1 I always thought that the choice of Nevada was made so the legal counsel of Covington could have a nice fling at the Reno casinos or a trip down the Tahoe ski slopes on AMRN's dime.

No one will ever change my mind. It was an egregious error to file in the 9th Circuit when New Jersey is in your backyard with a boatload of pharma companies and judges that are experienced in drug patent cases.

The decision to have the case filed in Nevada has to be the dumbest decision ever for AMRN. It destroyed the company.

Stock market is at all-time highs and AMRN is still foundering.


Cheers!
Flubber

OT...Novamax...If only this could happen to AMRN

Cheers!
Flubber

________________________________________________________________________


April 30, 2021 07:26 AM EDT PeopleCoronavirus
Stanley Erck bagged $48M in pay as he guided Novavax on a remarkable turnaround in the hunt for a Covid-19 vaccine
Kyle Blankenship
Managing Editor



Among pandemic success stories, only Moderna rivals Maryland-based Novavax’s remarkable rise from the bowels of obscurity to vaccine player. Driving that change was CEO Stanley Erck, who helped build the biotech’s supply chain from scratch — and he was paid handsomely to do it.

Erck scored a $48 million pay package in 2020, underscored by his work leading Novavax from near-bankruptcy to one of the remaining frontrunners for a Covid-19 vaccine, according to an SEC filing.

Erck’s pay skyrocketed from just $2.4 million in 2019, primarily tied to a whopping options package worth $44.1 million. Meanwhile, his base salary only slightly bumped up to $657,000 with $2.7 million in stock awards and $11,400 in a 401(k) match.

The fact that Novavax’s executives have profited mightily off the pandemic has been reported before and underscores the biotech’s gangbusters rise over the past year and change from a $4 penny stock on Jan. 1, 2020, to its current share price of $237.53 and $17.54 billion market cap. At one point, Novavax’s shares nearly topped $300.

According to our Jason Mast’s profile of the company’s recent work, Novavax is mostly on track to hit its stated goal of 2 billion doses of its recombinant Covid-19 shot despite the challenge of building a supply chain from scratch and running into raw material shortages that included bioreactor bags and Chilean tree bark.

Novavax was also the unfortunate recipient of a US government eviction in the summer from Emergent BioSolutions’ Baltimore Bayview site in favor of J&J — a decision that now reads as fortuitous given the production concerns that would later crop up at that site. Novavax, like J&J, accepted US government support for its manufacturing efforts but didn’t use US dollars to pursue R&D for its shot.

Now, with both J&J and AstraZeneca facing repeated safety concerns and production delays, Novavax is poised to become a third go-to option after Moderna and Pfizer/BioNTech’s mRNA vaccines. The biotech’s pivotal US trial is expected to read out in Q2.

But it’s not just Erck that has come out sitting pretty on the back of the pandemic. Gregory Glenn, Novavax’s president of R&D, notched $24.9 million in pay and CCO John Trizzino earned $21.3 million. Those pay packages would rank both men among the highest paid in biopharma in a non-pandemic year.

But the benefits also extended down to Novavax’s rank and file: The company’s median salary for employees was just slightly above $400,000 in 2020.

Investment in AMRN has been dead money for most everybody except swing traders on small moves. I would imagine that the majority of iHub commenters have an un-booked loss on their AMRN stock holdings. I have a loss and I have been invested for over a decade.

Do I think the stock is a dog? It's tough so say that it is not when compared against the general moves of the overall market. AMRN is just treading water and able to keep its head above water for now. How long can it hold out and be able to make it to the promised land?

The company has overcome multiple hurdles while JT was at the helm. Did he personally make the positive decisions that caused us to leap those hurdles? I really don't know. Looking back on it, the secondary offering appears to be a fortuitous decision. I believe that occurred when the stock was trading in the upper teens. Do you think AMRN would be able to float an offering today to garner the same amount of cash? I doubt it.

Vascepa? Great drug. AMRN? Bad luck. Judge Du's patent decision, even if overturned, has set this company back by a minimum of 2 years and the patent clock is still ticking.

I am still holding stock because I believe in the drug. Unfortunately, you can lead a horse to water, but you can't make him drink. Sales have been lackluster. Maybe a good portion of it is attributable to Covid. Insurance coverage still seems to be problematic. Entry by generics is a crushing blow.

I will not be adding to my current position even at today's depressed pricing. If anything, with AMRN, I have learned not to invest in a company that only has one product. It's do or die, depending on the ability of that product to penetrate the marketplace. So far, AMRN with Vascepa has been deficient on that metric.

I hope our new CEO has fire in his belly to shake things up and uses his European expertise in cardio drugs to push Vazkepa to the masses.

As always with AMRN, it is wait, wait, wait, until the next big pivot point, whether it be clinical trials, AdCom, ICER, FDA vote, patent case, patent appeal, Rule-60, Teva ruling, Covid test results, ad infinitum. It certainly tries one's patience. Somehow I see a horse pulling a wagon with a carrot suspended in front of his nose...that's AMRN.

As commenters have recently posted..."Hope is not an investment strategy". How true. We need our new CEO to get the ball rolling in the right direction. I have nothing but respect for JT and wish him well in his retirement. I do think it was time for a change to bring fresh blood in because whatever plan is currently in place, obviously was not impressing Wall Street.

Sorry for my long-winded take. I have to pose one question though. If any of the BPs were actually interested in AMRN, do you think the CEOs are breathing a sigh of relief that they did not offer BO in the range of $30+ per share 2 years ago? I think they must be saying to themselves..."I dodged a bullet".

Going to bury my head in the sand until more prominent events take place.

Cheers!
Flubber

@ Mf1979....Thero will certainly benefit from a buyout considering he has to be one of the highest individual shareholders in the company. But I have known other CEOs over the years. All of them very fine individuals, but they like control. I think if I was directing a company I would like to see it thru fruition to maximize shareholder value. I, as most on this board, see it, maximum shareholder value at this time can only be realized thru a buyout.

The company has been dealt a lot of blows over the years and seems to have overcome them all, except possibly the devastating Du decision on the patents. It' pretty obvious that the past 16 months have been dismal for shareholders. I am still holding original shares, hoping for the best (which would be break even for me), but am getting weary of seeing this stock greatly lag the general market. The opportunity costs are astronomical and the clock has been ticking on the now defunct patents.

Cheers!
Flubber

@ Bill B....unfortunately we have way too many of these 'interesting days'


Cheers!
Flubber

I would think that Thero's retirement indicates that there is not a BO on the horizon, or else he would have stuck around to bask in the glory.

Cheers!
Flubber

"Justice delayed is justice denied" eom

Cheers!
Flubber

OT...@jasberg & invest2992...Drop mic moment

Agree that Celine is terrific. My wife's favorite vocalist, but I think a relatively unknown to the USA singer, Floor Jansen from Holland, is the best. Kind of like Grace Slick on steroids times two! She sings for a heavy metal band called Nightwish...awesome, and I don't care for heavy metal.

This girl definitely has the pipes...the real deal. If you put 'Floor Jansen' or 'Nightwish' into a youtube search, more videos will pop up critiquing her singing than any other performer on the site.

Here are 2 video clips that show her range. First is from a European TV show singing a duet from Phantom of the Opera. The second is from live performance from outdoor concert in Waken, Germany. The song is quite long and worthwhile, but you can skip to the 8:00 mark to listen to an awesome 'drop mic' moment. I get goosebumps listening to this part of the song. This is one concert I would have paid big bucks to attend...unreal. The whole concert is available on youtube...about 1-1/2 hours.

Cheers!
Flubber

@ ramfan60 & ralphey....stock options

The selling of held stock to accumulate more share options at a lower designated price is common practice. The sales may be for tax purposes, but I doubt it.

I used to see it happen all of the time in a defense publication I used to receive. It would say so-and-so VP at Lockheed, Raytheon, or whatever, would sell 5K shares at $100/share and then buy 20K shares at granted option price of $25.

This is standard operating procedure when executives decide to exercise granted options. No money out of their pocket and they pick up additional shares. That is part of their compensation that was voted to them.

Forgive me if my knowledge of tax law is not up to snuff, but they would then pay any necessary capital gains tax at tax time on the proceeds of the 5K shares. Taxes would not be applicable on the newly bought shares until they are sold at a later date, their cost basis being the option price that was granted to the executive.

Cheers!
Flubber

@ couldbebetter....I think Amarin management has yet to wake up from their coma induced after being cold-cocked by the patent ruling.

Heck, my mind has been in a fog since that disastrous ruling. Thankfully marjac & HinduKush are clear-headed and pressing on with the case in pursuit of justice for shareholders (and to protect the integrity of scientific fact).


Cheers!
Flubber

OT...Bristol/Myers Irish patent and IRS troubles.

FWIW.

Cheers!
Flubber
________________________________________________________________________



April 1, 2021 10:01 AM EDT
PharmaRegulatory

Bris­tol My­ers faces $1B+ tax fight af­ter ac­ci­den­tal dis­clo­sure re­veals al­leged off­shore patents scheme — re­port
Kyle Blankenship
Managing Editor


The IRS has bat­tled Big Phar­ma for years over off­shore patent trans­fer schemes, which it said have bilked the pub­lic in­ter­est by bil­lions of dol­lars. Now, loose lips at the agency have re­vealed its pur­suit of an­oth­er drug­mak­er — Bris­tol My­ers Squibb — that it says is on the hook for more than $1 bil­lion in back tax­es.

Bris­tol My­ers could face near­ly $1.4 bil­lion in back tax­es the IRS be­lieves it evad­ed pay­ing as part of a scheme to move its patent rights from the US to an Irish sub­sidiary and reap the in­come write-offs, the New York Times re­ports.

The dis­pute was re­vealed as part of an ac­ci­den­tal dis­clo­sure from the agency last spring, the Times said, which was al­most im­me­di­ate­ly pulled from pub­lic view.

At the cen­ter of the IRS’ claims is Bris­tol’s ef­fort in 2012 to es­tab­lish an Irish sub­sidiary as a ve­hi­cle to shut­tle US drug patent rights over to a coun­try with low­er cor­po­rate tax rates. In a scheme known as amor­ti­za­tion, com­pa­nies can write off the val­ue of an as­set — patents, for in­stance — from their tax­able in­come over a pe­ri­od of time. Bris­tol had al­ready writ­ten off the val­ue of its patents in the US, the IRS said, and set up a plan to move those rights to Ire­land, where that val­ue had not yet been writ­ten off.

The out­come? Around $1.38 bil­lion in back tax­es, the IRS said.

“Bris­tol My­ers Squibb is in com­pli­ance with all ap­plic­a­ble tax rules and reg­u­la­tions,” the com­pa­ny said in a state­ment. “We work with lead­ing ex­perts in this area and will con­tin­ue to work co­op­er­a­tive­ly with the IRS to re­solve this mat­ter. Be­yond that, we don’t com­ment on on­go­ing reg­u­la­to­ry mat­ters.”

The scheme was lu­cra­tive, the Times re­port­ed. The com­pa­ny’s ef­fec­tive cor­po­rate tax rate was -7% in 2012 com­pared with 25% in 2011. The dif­fer­ence was so stark that an­a­lysts re­port­ed­ly quizzed ex­ec­u­tives on the dis­par­i­ty dur­ing a Q4 2012 earn­ings call — ques­tions that Bris­tol re­fused to an­swer.

Mean­while, Bris­tol My­ers’ plan re­port­ed­ly got a sign-off from two cor­po­rate au­di­tors, PwC and White & Case, in late 2012. Both firms sent lengthy let­ters to Bris­tol es­sen­tial­ly clear­ing the scheme — even af­ter Mer­ck had been cit­ed by the IRS back in 2006 for a sim­i­lar off­shoring ef­fort that saved it $1.5 bil­lion in fed­er­al tax­es over 10 years.

In that case, Mer­ck of­floaded its US patents to a Bermu­da sub­sidiary, which it then turned and paid for ac­cess to those patents, the IRS said. The amor­ti­za­tion scheme wasn’t even unique to Mer­ck: Oth­er big-name drug­mak­ers such as J&J, Pfiz­er and Ab­bott have all been im­pli­cat­ed in sim­i­lar plans in the past.

In a 2018 re­port, Ox­fam es­ti­mat­ed that off­shoring schemes were sav­ing those four drug­mak­ers around $2.3 bil­lion per year in US fed­er­al tax­es. In to­tal across nine de­vel­op­ing coun­tries in­clud­ing the US, Ox­fam es­ti­mat­ed the firms were writ­ing off around $3.7 bil­lion per year.
________________________________________________________________________

@ marjac....I think this is a better description of your scholarly efforts to rectify the disastrous 9th Circuit ruling...LOL!

OT...AdComm / Biogen's aducanumab

Interesting that AdCom board is writing letter to FDA recommending that aducanumab be pulled due to conflicting statistics in the clinical trials.

For those suffering from Alzheimer's Disease, I was hoping for anything that works to stem the cognitive decline. Although years off, also hoping that the BRAVE study at Wisconsin VA hospital will show positive results of Vascepa restraining the effects of Alzheimer's.


https://endpts.com/in-highly-unusual-op-ed-3-aducanumab-adcomm-members-again-call-on-fda-to-reject-biogens-alzheimers-drug/


Cheers!
Flubber

@ golden flyer....'execution'...

In the immortal words of the late John McKay, when coach of the lowly Tampa Bay Buccaneers, he was asked by a reporter what Coach McKay thought of his team's execution....

McKay' deadpan response...."I'm all for it"

CLASSIC!!


Cheers!
Flubber

OT @ ralphey....My wife was a juror years ago on an assault & battery case...

One female crackhead claimed another female crackhead busted her over the head with a tire iron to steal her crack cocaine.

I died laughing when I heard that this even made it to trial.


Cheers!
Flubber

@ golden flyer...You may be right, but what do the amount of shares have to do with it? It's total value and that is all. Do a reverse stock split... you receive 1 for 10 and you reduce the number of outstanding shares to 40 million....value is still the same

Cheers!
Flubber

@ Pterion....Love your enthusiasm, but not sure how long you have been invested in AMRN. We have all heard enthusiastic claims for years about AMRN and Vascepa only to get a punch to the gut every single time.

This stock never catches a break. It just kills me watching AMRN while other sketchy stock issues without fundamentals catch fire and their share price rockets to the moon.

I've been invested for over a decade. I am holding my current position. Have booked losses on call-options (stupid me!).

To be honest, I still see major upside potential in the stock if things fall our way for a change, but I am too shell-shocked to add to my current position. This stock has made me weary.

If one piece of investment advice that was handed to me thru my plunge into AMRN, it is to invest in a company with more than one product. It is 'do-or-die' with AMRN and its only drug, Vascepa.

As always,
Cheers!
Flubber

@ Number sleven....Thank you very much for your explanation regarding infringement based upon the labeling.

Cheers!
Flubber

OK....can someone explain in layman's terms the infringement...

I may be wrong, but this is the way I see things...

1. AMRN produces Vascepa and markets it for both trigs and CVD.
2. Hikma produces generic vascepa and can ONLY market it for trigs.
3. I go to the doctor. He says I have a heart condition and my heart condition would be helped by taking 4grams daily of icosapent ethyl.
4. He writes a prescription for me.

Question? Is the doctor obligated to write down "VASCEPA ONLY....NO SUBSTITUTIONS" ??
Or can he be a nice guy and try to save me (or my insurance company) some bucks by writing prescription for "4 grams of icosapent ethyl" or "generic Vascepa OK".

I get the drift of the infringement, but if Hikma labels their product for trig control only, how are they infringing?

We all know that the 'wink-wink' substitution will take place, but I am trying hard to see the infringement by Hikma. Would not the infringement be in the hands of the doctor?

Sorry for the long winded question.

Cheers!
Flubber

OT..@ lizzy241 & marjac "Who was Pink & Floyd?"

Here's your answer...

https://images.app.goo.gl/EKZf3iVyxYy2cMzn7


Cheers!
Flubber

@ meowza....Tocopherol and anti-oxidant properties

Any chemists out there???

https://www.researchgate.net/publication/240804014_Vitamin_E_Mechanism_of_Its_Antioxidant_Activity



Cheers!
Flubber

OT @ jasbg RE: singer Floor Jansen

Just to show you the range of Floor Jansen, here is a link showing her singing Phantom of the Opera with the guy that played the lead in the Dutch version of the musical. This is taken off of some TV show from Holland.

She kills this along with her male counterpart. I read somewhere that Floor Jansen has had operatic training. She has a strong voice and a great range.

Enjoy!

@ marjac....LOL...too funny.

In all seriousness, thank you and HK for all you have been doing behind the scenes to try to rectify what we all see as a grave injustice to AMRN due to the adverse legal decision regarding the patent.

I have been away from this board for quite some time to cleanse the soul. Believe me when I say it does wonders to give your mind a break from the continuing drama that surrounds our little AMRN investment.

Sincere good luck in your endeavors with the legal filings. I must admit that I have learned quite a bit by being on this board that covers a myriad of subjects such as statistics, CVD, clinical trials, corporate dealings, patent law, the workings of the judicial system, etc. I'll chalk up all of that learning as something positive going forward, but in reality I would have just preferred "SHOW ME THE MONEY" as stated in the movie 'Jerry Maguire'.


And for those on the board that are discussing music, you should check out the heavy 'symphonic' metal band out of Finland....Nightwish. Absolutely incredible female lead singer, Floor Jansen. She is the second coming of Grace Slick on steroids (times 2). For anybody interested, the attached is link to 2013 live concert in Wacken, Germany. Best damn stage show I have witnessed. Sound quality is awesome for a live concert. Disclaimer: I'm not a metal fan, but I love this band. Best to listen to video with headphones if you have them.

@ marjac and hk....thank you

https://www.micechat.com/118815-reasons-to-celebrate-2/5738dc204513cfbbc794ebe37c1961daaccfd3c16a58a588774862aac2388414/


CHEERS!
Flubber

I came back to the AMRN iHub board yesterday with my first post in quite some time. I actually stopped following the stock until a business acquaintance who is taking V recently mentioned that he was considering establishing a position again after selling at a loss last year. He asked my thoughts.

I told him as much as I want AMRN to succeed, I think his cash would be better positioned with just about any firm other than AMRN. Unfortunately AMRN is a one-trick-pony with only Vascepa in its stable. It lives and dies on the performance of Vascepa. Judge Du effectively killed the company with her adverse ruling last March.

AMRN had just about every hurdle tossed at them and cleared them all until the fiasco with the 9th Circuit in Reno. I will go to my death believing that the incredible screw-up of filing the lawsuit in the liberal 9th Circuit was due to Covington most likely suggesting to file in the 9th. It was mentioned on this board that a member of the Covington team was a former clerk in the 9th Circuit. I'll bet my bottom dollar that the Covington team thought the lawsuit had extraordinary odds in AMRN's favor and why not go to out west in January to experience the casinos in Reno and the ski slopes in Tahoe on AMRN's dime?? Heck, the clerk knew of all of the hot spots to hit.

I've been in this stock for over a decade and am currently underwater. I guess like many here, I was hoping for the best. For me, this stock has been worse than dead money during the greatest bull run the stock market has ever seen. Due diligence?? I wish I was like my brother that bought 10K of Novavax (NVAX) back in October 2019 for about $4.50/share. Stock is at $275 today. He bought it based upon vaccine for the normal winter flu season. Little did he know that COVID would hit and NVAX would get gov't funding and the stock took off to the moon.

He gets all of the luck. I get stuck with AMRN...SHEESH! So frustrating. Sell the company to try to get us long term investors a few more bucks. Nobody is getting rich off of this company. Even JT with all of his options would have been far better off cashing out in the $20s.

As always,
CHEERS!
Flubber

@sts66 re: generic V ingredients

Yes, it appears that generic V has a real mish-mash of ingredients as compared to the real Vascepa. I guess the ingredients are FDA approved. What caught my eye was the number of alcohol formulations in Hikma's product.

It was mentioned that AMRN has specific patent covering encapsulation to prevent oxidation of the product. I wonder if Hikma has gotten around that troublesome issue by adding alcohol as a preservative. I am not a chemist, but per attached white paper, that might be the case.

https://www.researchgate.net/publication/318380276_Antimicrobial_Preservatives

(I've been away from the iHub board for a number of months and is has been soul-cleansing....Now my interest is piqued once again viewing the trials and tribulations of our favorite drug company, AMRN!)

Cheers!
Flubber

@ jasbg....Do you mean the Global Organization of EPA & DHA (GOED) ??

Here is link if that is what you are looking for...

https://goedomega3.com/


Cheers!
Flubber

Cytokinetics cardio drug reports so-so findings....

Cheers!
Flubber

____________________________________________________________________
Updated: Amgen's big cardiovascular bet with Cytokinetics hits PhIII primary but dramatically disappoints investors




Jason Mast
Associate Editor




A closely watched heart drug from Amgen and Cytokinetics has both hit the primary endpoint on a major trial and dramatically disappointed investors.

In the 8,250-person study, the drug reduced the odds of hospitalization or other urgent care for heart failure by 8%, a statistically significant result. But the drug failed to help high-risk patients live longer, an endpoint that analysts had been following as the key marker for whether the drug could make a large impact.

“Trial technically worked,” Mizuho’s Salim Syed wrote in a note to investors, “but failed on what was really needed here to be a foundational medicine, in my view, which is CV death.
”
Cytokinetics shares fell 43% on the news, from $23.66 to $15.33, wiping away a major spike the company had seen in May, when a MyoKardia drug with similarities proved successful on multiple endpoints. Amgen was down 4.6%, from $257.67 to $245.82.

The two companies have collaborated on cardiovascular R&D since 2007.
A Cytokinetics spokesperson said in an email that the data is only a few days old and that they hoped sub-group analyses set to be unveiled at the American Heart Association show how best to use the drug. Syed suggested that it was possible the inpatient population, which is sicker and represented 25% of the trial enrollment, had driven the results down.

“Company believes this is still an approvable drug, saying we need to wait for AHA,” he said. “How effective will this drug be commercially if approved? In my view, without CV death benefit, the drug probably won’t be a foundational medicine and do the $4Bn in WW end-user sales that we had originally thought (consensus is ~$3.5Bn). But is it a zero? Maybe not.”

That sub-group data could only yield an approval, though, if they had defined the sub-group ahead of time, SVB Leerink’s Geoffrey Porges argued. He said that the study was well-powered to find a result on cardiovascular death.

“We believe the future for omecamtiv is highly uncertain unless the company finds a subset with clear benefit (particularly if prospectively defined),” he said, adding that he expects Amgen to discontinue other ongoing studies.

Analysts raised concerns not only about the lack of mortality data but also about the effect size on the primary endpoints, which they widely expected to be larger. Syed said it “barely” crossed significance, with the confidence interval approaching 1.

Baird’s Brian Skorney compared that effect to the 26% reduction AstraZeneca’s Farxiga saw in a recent, 4,700-person study, calling it “deeply disappointing.” He noted Farxiga is available for less than $10,000 per year.

“While cross-trial comparisons always should be taken with a grain of salt as patient populations and clinical endpoints often slightly differ,” he said, “we believe the top-line results from GALACTIC-HF suggest omecamtiv mecarbil is unlikely to be a commercially attractive product even if it should gain approval (which we view as unlikely.)”
The drug, omecamtiv mecarbil, works by targeting myosin, a protein that converts chemical energy into mechanical force in the heart. The drug was supposed to activate the protein, helping the heart contract.
MyoKardia’s drug, mavacamten, also targeted myosin but inhibited it, helping correct a rare cardiomyopathy. The company, acquired this week by Bristol Myers Squibb, also has a myosin activator in Phase II.

This would not be the first significant disappointment for Cytokinetics, a company that has worn the vicissitudes of biotech over its 23-year history. The South San Francisco-based company invested in two ALS drugs over the last decade, but struggled to hit key endpoints in trials for the difficult-to-treat conditions. One ALS drug, reldesemtiv, is still in development and set to enter Phase III this year.

In public statements, neither executives from Amgen and Cytokinetics touted the study as a success nor indicated whether they would submit for FDA approval. Cytokinetics’ R&D chief Fady Malik said the trial “provides insight” and that “they look forward to further data analyses.” Amgen R&D chief David Reese said simply they “further the understanding of treating heart failure.”

“The outcomes observed in GALACTIC-HF further the understanding of treating heart failure, a devastating disease in which half of heart failure patients will die within five years of initial hospitalization,” Reese said. “At Amgen, we remain committed to developing and delivering transformative medicines that improve the lives of patients with cardiovascular disease.”

Full data will be presented at the AHA in November, but the early readout also spells bad news for one other company, Royalty Pharma. In 2017, the company paid $90 million for a 4.5% royalty.
Correction: An earlier version of this article misstated the terms of a royalty deal with RTW. It does not cover omecamtiv mecarbil.

New article regarding cardio drug development...

I like you guys so much "I'M BACK"...with an article I thought you might like regarding cardio drugs (basically overlooking of cardio drugs in preference to cancer drugs).

Still holding tight to my AMRN shares hoping for a miraculous turnaround.

Cheers!
Flubber

https://www.biopharmadive.com/news/pharmacquired-heart-drug-deals-myokardia/586434/?utm_source=Sailthru&utm_medium=email&utm_campaign=Issue:%202020-10-08%20BioPharma%20Dive%20%5Bissue:30137%5D&utm_term=BioPharma%20Dive

Endpoint News article....

Cheers!
Flubber


Amarin loses patent appeal and their brief grip on a cardiovascular, fish oil empire

Jason Mast
Associate Editor



Amarin’s briefly-held fish oil empire has slipped from its grasp, and now appears gone for good.
A US federal appeals court refused on Thursday to overturn a March ruling that stripped the Irish drugmaker of its patents on the fish oil-based heart drug Vascepa, opening the door for generic alternatives to hit the market. The ruling means that Amarin’s chance of turning an expanded approval from last December into blockbuster revenues has essentially vanished.

Investors responded accordingly, with the stock falling 7% from $5.04 to $4.67. The drop-off likely would have been steeper, but high odds of a patent loss had already been baked into the stock’s price, with Wall Street beginning to signal its skepticism in the winter and the stock dropping 70% when the first patent ruling came down on March 30. Vascepa is their only product.

The announcement yesterday of the judges that would serve on the appeal panel provided the final nail. Analysts considered the judges collectively unfavorable toward Amarin, and the stock sold off 30%.
In a statement, Amarin CEO John Thero said it will “vigorously pursue available remedies,” which could include one last form of appeal, but analysts have largely moved on. In a note, Stifel’s Derek Archila said the questions that Amarin now face center on Europe, where Vascepa remains under patent protection. He estimated $650 million in peak sales there, but noted that the drug still has to be approved and the company still has to secure reimbursement.

“So we don’t think 2021 sales of Vascepa in the EU are likely to be meaningful,” Archila said. “We think the fact AMRN was not able to partner the EU rights for Vascepa for a meaningful sum and chose to go-it-alone could mean partners viewed this opportunity to be a more modest one or challenging to execute on, thus, we are conservative with our peak sales estimates and sales ramp in the EU.”

Still, there are questions about how much market Vascepa could still grab in the US. Archila noted that Vascepa is complex to make, potentially limiting how much generic competition emerges. And Amarin said in a statement that given how current competitors may likely have limited supply, they will for now maintain their sales and promotional infrastructure.

Archila cautioned, though, that cutting in the US sooner might be “prudent” to prepare for the costs of launching in the EU. While saying they will continue to fight in the states, Thero emphasized the opportunities elsewhere. “We are particularly excited about the anticipated commercialization opportunities for Vascepa in Europe as we prepare for expected approval and launch in early 2021,” he said, also noting markets in China and the Middle East.

The court ruling caps a rollicking two years for Amarin. In September 2018, the specialty pharma outlet first announced positive data from a Phase III trial showing its omega-3 fatty acid product had reduced the risk of a cardiovascular event — such as a heart attack — in a large group of at-risk patients. That sent the stock soaring 288% as analysts talked about a $2 billion market opportunity.

As more detailed data came back, the stock stayed high and buzz started forming around a possible buyout from a larger company. Amarin decided to go it alone, perhaps in part because questions around the company’s intellectual property hovered over its success. On December 12, the FDA handed a blockbuster expanded approval. The patent suit, which pitted Amarin against generic drugmaker Dr. Reddy’s and Hikma Pharmaceuticals, started a month later.

A judge decided against Amarin, ruling that claims in its patents that Dr. Reddy’s and Hikma infringed on were “obvious.” The appeal court did not hand down a formal opinion.

@ RobinF…..my take on the judges...

The appeal panel of judges rubber stamped Judge Du's opinion because it required no work and now they can make their tee-time at the golf course

I also think that the terrible mistake of picking the liberal 9th Circuit to file the lawsuit was done so that the legal team could have a nice winter vacation in the casinos of Reno and head to Tahoe for some skiing. I'm not being cute with this last statement.

Cheers!
Flubber

I'M BACK!!! (sorry to say)

I took a hiatus from this board most of the summer figuring that not much would be happening until the appeal arguments. Sheesh...what a disaster. Great drug...terrible company and patents.

I must admit that I enjoyed taking time off from the iHub board but I did miss you guys and girls. I learned quite a bit from all members, but unfortunately like many here, my investment is underwater. I still say that whomever decided to file the lawsuit in the 9th Circuit should be drawn and quartered.

I look at my investment today in AMRN which I have had for a decade vs. the investment my brother made less than a year ago in NVAX and I want to throw up.

Not sure if I will throw in the towel and move onto something else. I guess we can hold out for the European market, but I expect it will take years for the stock to approach $10/share.

It's hard to admit our investment analysis was wrong and that everything hinged on one judge's decision. It's crushing to admit defeat when so many positive aspects can be associated with Vascepa. Cripe, I'll probably have to go on the stuff now after the roller coaster ride we have been on for what seems like an eternity.

I'll probably monitor this board from time to time. I want to thank everybody for all of the wisdom they tossed out there. I wish I had a better response of hope but I think this is the last dagger for the US market, a sizable one at that.

Cheers! (tear rolling down the cheek)
Flubber

@ ziploc-1...'Overcoming Obviousness Rejections'



https://www.finnegan.com/images/content/2/5/v2/255327/PUBLISHED-Lexis-Practice-Advisor-Obviousness-Overcoming-Obvi.pdf


https://www.finnegan.com/images/content/2/0/v2/205749/PUBLISHED-TLI-SDL-2018-Midwest-IP-Institute-Top-Tips-for-O.pdf


https://www.lexology.com/library/detail.aspx?g=bf2505e2-707b-4c05-bb1e-ef60c0e063dc



Cheers!
Flubber

OT...Sanofi has $23 billion of cash to burn...

And AMRN is just flapping in the wind....sheesh...
I'm starting to think 'Sell in May and go away"

Article is from Endpoints.

Cheers!
Flubber

________________________________________________________________________

May 27, 2020 07:03 AM EDT BioregnumR&D


Sanofi CEO Paul Hud­son has $23B burn­ing a hole in his pock­et. And here are some hints on how he plans to spend that



Bioreg­num Opin­ion Col­umn by John Car­roll

Sanofi has reaped $11.1 bil­lion af­ter sell­ing off a big chunk of its Re­gen­eron stock at $515 a share. And now every­one on the M&A side of the busi­ness is fo­cused on how CEO Paul Hud­son plans to spend it.

Af­ter get­ting stung in France for some awk­ward pol­i­tick­ing — sug­gest­ing the US was in the front of the line for Sanofi’s vac­cines giv­en Amer­i­can fi­nan­cial sup­port for their work, ver­sus lit­tle help from Eu­ro­pean pow­ers — Hud­son now has the much more pop­u­lar task of man­ag­ing a ma­jor cash cache to pull off some­thing in the or­der of a big bolt-on. Or two.

Which is per­fect for Hud­son’s pur­pos­es in spurring a turn­around at the slug­gish gi­ant — an­oth­er top­ic he’d like to fo­cus on more.

Ge­of­frey Porges at SVB Leerink did the math. With around $10 bil­lion in cash re­serves in the bank and $13 bil­lion lined up on the Re­gen­eron stock, Porges is ex­pect­ing some quick move­ment on the buy­out front fol­low­ing Hud­son’s deal to ac­quire Syn­thorx for $2.5 bil­lion — putting them on the trail for more on­col­o­gy as­sets to go with the new R&D strat­e­gy.

As GSK and Gilead would demon­strate, you can make a quick splash in can­cer these days, so it’s a pop­u­lar M&A fo­cus af­ter years of record biotech in­vest­ments in the field.

Porges likes gene ther­a­py tech as the tar­get this time.

On the Q1 earn­ings call, Sanofi’s CEO Paul Hud­son al­so in­di­cat­ed that his per­son­al con­trac­tu­al re­stric­tions that pre­vent­ed him from be­ing in­volved in a non-No­var­tis gene ther­a­py in­vest­ment end­ed in late Feb­ru­ary, which sug­gests that a sig­nif­i­cant in­vest­ment in a gene ther­a­py plat­form could be pos­si­ble. We cer­tain­ly ex­pect a M&A deal of de­cent size ($5bn) in the com­ing months for Sanofi.

All the oth­er an­a­lysts have been do­ing the same kind of cal­cu­la­tions, along with a mob of small in­vestors look­ing for a nice score. Pick the right tar­get, and you can pick up a nice pre­mi­um overnight.

Of note, Sanofi’s de­ci­sion to sell off its Re­gen­eron shares 7 months be­fore the lock­up ex­pired al­so frees up the top ex­ecs at Re­gen­eron for their own M&A moves. And that will help fur­ther bol­ster val­u­a­tions for biotechs which have the cash re­serves, R&D buzz and share prices nec­es­sary to raise mon­ey.

Far from be­ing bio­phar­ma’s Wa­ter­loo, the in­dus­try is look­ing pret­ty good dur­ing the pan­dem­ic. More sig­nif­i­cant M&A now — not the bot­tom-feed­ing ex­pe­di­tions we’ve seen at the likes of Alex­ion — would on­ly im­prove that pic­ture.

AUTHOR
John Carroll
Editor & Founder
john@endpointsnews.com
@JohnCendpts
John Carroll on LinkedIn

OT...NEJM 'Preliminary Report on remdesivir'

https://www.nejm.org/doi/full/10.1056/NEJMoa2007764


Cheers!
Flubber

OT @sts66...Stalingrad surrender

sts...attached is recent youtube video detailing the surrender by General Paulus to the Russians. His first interrogation is quite fascinating. The guy was between a rock and a hard place. Hitler wouldn't let Paulus break out of the pocket. The Russians were prepared to annihilate every last remaining German soldier. As has been mentioned..."war is hell."

This little documentary is a first hand eyewitness account with notes taken as to the conversation between Paulus and the Russian generals. The eyewitness was a Russian photographer.