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Off finding other stocks to lose money on!
I got out of ELTP in October 2018. I had a lot of shares but no where near 20 million!
Still alive and kicking!
What about the infamous combo pill? Statin plus Vascepa.
That dead? Couldn't that be a way around some of this?
HIKMA PR
LONDON, Sept. 3, 2020 /PRNewswire/ -- Hikma Pharmaceuticals PLC (Hikma), the multinational pharmaceutical company, announces that the US Court of Appeals for the Federal Circuit today upheld a ruling by the US District Court for the District of Nevada finding that Hikma's generic version of Vascepa(R)1 (icosapent ethyl) 1gm does not infringe any valid claim of six key Amarin-owned patents. Hikma received FDA approval for the product in May 2020 and is working towards a launch.
Vascepa(R) is a prescription medicine that is indicated, in part, as an adjunct to diet to reduce triglyceride levels in adult patients with severe (>= 500 mg/dL) hypertriglyceridemia. According to IQVIA, US sales of Vascepa(R) were approximately $1.1 billion in the 12 months ending July 2020.
"We are very pleased with the Federal Circuit's swift decision and to be one step closer to launching a generic version of this important medicine for US patients and healthcare providers, helping us to continue putting better health, within reach, every day," said Brian Hoffmann, President of Hikma Generics. "Today's decision demonstrates Hikma's ability to successfully challenge patents on important medicines and to provide value to our customers and millions of patients across the United States."
I'd take $7.00 now. Unbelievable.
If JT doesn't sell how much is US market now worth?
They can still sell the branded drug and they can augment that with their own generic. They have Europe and ROW. The drug still works. Can't be completely worthless. Right?
Is there a link to the Jeffries/Yee call?
https://thefly.com/landingPageNews.php?id=3155049&headline=AMRN-Amarin-participates-in-a-conference-call-with-Jefferies
Thinking about the coming months.
Appeal decision is expected in what, Nov/Dec perhaps?
What "negative" news could come between now and then? I don't see much else?
But between now and then we could see any of the following positives:
Covid-19 trial results?
NASH trial results?
Evaporate results?
EU Approval? Could be quite huge.
Settlement w/ Hikma? (small chance but would be a huge needle mover)
DTC launch (seems imminent..but I don't expect that to be a big needle mover)
Seems to me between now and Nov/Dec. it's a good at least short term buy as odds of "good news" coming out outweighs odds of bad news?
Wold appreciate a reality check!
Thanks!
Hike
My wife has CRPS so actually this is quite informative!
Thanks!
Pfizer said it plans to use that cash to pay down its own debt.
Good read on patent issue:
https://www.markmanadvisors.com/blog/2019/12/3/can-amarins-patents-protect-vascepa-from-generics
Can Amarin’s patents protect Vascepa from generics?
Zachary Silbersher
Amarin Pharmaceuticals ($AMRN) will be going to trial soon to protect Vascepa® against generic competition. Amarin has asserted 15 claims from six patents against ANDAs filed by Hikma, Dr. Reddy’s and Teva. What are the issues to be addressed at trial?
This post provides an overview of the issues to be litigated at the upcoming bench trial scheduled for January 2020. There are numerous other questions currently surrounding this case. Will the parties settle before the trial? What dynamics are motivating the likelihood of settlement? Why did Teva settle, and does anything from that settlement read through to the trial? How does the REDUCE-IT study and Amarin’s bid to add a cardiovascular indication to Vascepa® impact this case? Can Amarin use the REDUCE-IT study in the upcoming litigation trial to prevail? If the generics launch at-risk, could they face exposure for off-label prescriptions of the cardiovascular indication? We will potentially address these and other questions regarding Vascepa® in upcoming blog posts.
Background
Vascepa® is indicated to treat patients with hypertriglyceridemia, which are severely high levels of triglycerides (“TGs”) above 500 mg/dl. The active ingredient in Vascepa® is highly purified omega-3fatty acid called ethyl-eicosapentaenoic acid (“ethyl-EPA” or “EPA”).
Amarin was not the first drug to treat hypertriglyceridemia with highly purified omega-3fatty acid. An earlier drug, Lovasa®, also used EPA in combination with another omega-3 fatty acid called DHA, to treat hypertriglyceridemia by lowering TGs. Another drug, Epadel, distributed in Japan, used only EPA to reduce TGs and was supposedly in clinical trial use before the priority date of Amarin’s patents.
Nevertheless, Amarin claims that it was the first to patent a formulation of EPA that lowered TGs without also increasing “bad” cholesterol (LDL-C). Though Amarin’s patent applications faced numerous rejections from the Patent Office as obvious, the patents were eventually allowed after Amarin showed that its dosage regime for pure EPA yielded unexpected results, namely, it allegedly does not increase of LDL-C levels and it reduces apolipoprotein B (“Apo-B”) levels.
Amarin’s case against the generics has been pending since 2016, and the case is scheduled to go to trial in January 2020. In late October, the district court in Nevada, where the case is pending, issued a ruling on cross-motions for summary judgment. That ruling essentially narrowed the issues to be litigated at the upcoming trial down to two principle disputes. First, the generics argue they do not induce infringement of the patents, and second, the generics argue that even if they do infringe, the patents are invalid as obvious.
Infringement
The patents are directed to methods of treatment. Because those methods are technically performed by the administering physician, and not by a generic pharmaceutical drug company, Amarin has been compelled to argue that the generics’ infringement is indirect rather than direct. Specifically, Amarin has argued that the generics will induce doctors to infringe the patents. The generics’ proposed labels are substantially similar to Amarin’s FDA-approved label. Thus, to show induced infringement, Amarin will effectively argue that the generics’ proposed label instructs doctors to perform each claimed element of the asserted patents.
The problem for Amarin, however, is that the patents require administering the drug for at least 12 weeks, but the label does not specify any duration for drug administration. Accordingly, the generics have argued that they cannot induce doctors to infringe the patents—including the 12-week limitation—because their proposed labels, which basically copy Amarin’s label, says nothing about how long to administer the drug.
Amarin’s response is that the label says more than the generics suggest it does. Specifically, the label refers to the Phase 3 MARINE clinical trial, where patients were administered the drug for 12 weeks. Based on that, Amarin argues that prescribing physicians would be encouraged to follow the time-period used in the clinical trial that backed up approval of the drug. Amarin also argues that because hypertriglyceridemia is a chronic condition, thus requiring indefinite treatment, doctors would understand that the drug should be prescribed indefinitely. That would therefore be at least 12 weeks.
The court has ruled that this issue is essentially a fact question on which it must hear expert testimony—namely, would doctors really read the label and determine the drug should therefore be prescribed for at least 12 weeks? More importantly, the court indicated it was persuaded, at least initially, by Amarin’s argument that because hypertriglyceridemia is a chronic condition, doctors would be encouraged to prescribe the drug indefinitely, which could necessarily encompass twelve weeks.
The court cited earlier precedent from a Hatch-Waxman case involving the drug Multaq® that also held that a label lacking a duration for treatment nevertheless induced infringement of a patent requiring 12-month administration for a condition that was also chronic. At the upcoming trial, the court will no doubt pay attention to the expert testimony on this issue, but barring any surprises, the court has for now indicated that it is inclined to side with Amarin on the issue of infringement.
Some of the patents require additional effects, such as specific lipid effects through administration of the drug (e.g., reducing Apo-B). For similar reasons, the court has allowed the issue of inducement on these claims to also go to trial. Either way, it bears emphasis that Amarin is not required to succeed on all 15 patent claims at trial to be entitled to an injunction against the generics launch. All of Amarin’s patents expire in 2030, and therefore, success on only a single patent claim theoretically could suffice.
Invalidity
The patent claims generally require, among others, the following elements: pure EPA, administered to patients with TG levels in excess of 500 mg/dl, 4 grams/day, for 12 weeks, without co-administration of DHA, where LCL-C levels are not increased. Among other things, some of the patent claims also require reduction of Apo-B. To show that the dosing regime and method of treatment was obvious, the generics rely principally on four prior art references: Lovasa®, Mori 2000, Hayashi and Kurabayashi.
During prosecution, Amarin argued that it was “unexpected” that administering pure EPA, without concomitant administration of DHA, to patients with high TG levels, did not increase LDL-C levels. The Examiner initially refused to allow the patents on this basis because the prior art suggested that a former drug, Epadel® (highly purified ethyl-EPA) could be administered to patients with TG levels under 500 mg/dl without a major impact on LDL-C levels. Thus, according to the Examiner, it was not “unexpected” that the same result could occur for patients with higher LDL-C levels.
Instead, the Examiner allowed the claims after concluding that it was “unexpected” that administering 4 g/day of EPA to patients with high TGs would decrease Apo-B levels. In particular, the Examiner concluded that the prior art showed no change in Apo-B levels from administering EPA to patients with TG levels below 500 mg/dl. In addition, Amarin’s MARINE study showed that this result was shown for 4 g/day, but not for 2 g/day, which evidenced certain criticality of the 4 g dose. The Examiner also concluded that there was a long-felt need for a drug for patients with high TG levels that did not also increase LDL-C levels, which is associated with cardiovascular disease, especially given that the two prior drugs approved for treatment of high TGs (Lovasa® and Triplix®) appeared to raise LDL-C levels.
EPA was previously sold as Lovasa® to treat high TGs. Lovasa® was not pure EPA, but rather a combination of EPA and DHA. Lovasa® was apparently administered to patients with high TG levels, with an attendant decrease in those levels. One of Lovasa®’s side-effects was increased LDL-C (bad cholesterol) levels, especially at high TG levels. Amarin argues that increased LDL levels were correlated to the severity of TG levels—thus, higher TG levels led to increased bad cholesterol levels when taking Lovasa®.
The generics rely upon Mori 2000 to show that, allegedly, DHA was responsible for increased LDL-C levels, rather than EPA. Mori 2000 discloses a study in which three groups of approximately 20 men were administered EPA, DHA or placebo, respectively. Thus, Mori 2000 is one of the few studies that examined the differences between individual administration of EPA versus DHA. On the one hand, the study showed lower increase of bad cholesterol with DHA versus EPA, namely, 8% for DHA and 3.5% for EPA. (The decrease of 3.5% for EPA was not considered statistically significant.) Given this, the generics argue that it was obvious that DHA, rather than EPA, was responsible for increasing LDL-C levels for Lovasa®, and thus, it would have been obvious to a person of skill that administering pure EPA would not increase LDL-C levels.
On the other hand, Amarin criticizes the study for its relatively small sample size, where none of the patients allegedly had TG levels in excess of 500 mg/dl, and both drugs yielded increased LDL levels. Specifically, Amarin claims that the baseline TG levels for the EPA group was 11% lower. This was significant, according to Amarin, since they also claim that increased LDL-C levels from taking EPA or DHA (principally from Lovasa®) was a function of baseline TG levels. Thus, the fact that none of the patients in the Mori 2000 study had baseline TG levels as high as required by the claims, according to Amarin, mitigates the showing of obviousness.
Hayashi was a study that disclosed 1.8 gm per day of EPA-E over eight weeks to patients with TG levels of 300 ± 233 mg/dl. (Based on this description, the parties dispute whether the Hayashi study would have statistically included patients with TG levels in excess of 50 mg/dl.) The study showed that TG levels decreased (41%) as well as LDL-C (7%) and apolipoprotein B (7%). Amarin critiques Hayashi because it was a relatively small size, the purity of EPA was not disclosed, and there is no proof that any patients had TG levels in excess of 500 mg/dl, or any data on patients that might fit into this category. This is also likely to be an issue of dispute at the upcoming trial.
Kurabayashi was a study that disclosed pure EPA (96.5%) along with estirol at 1.8 g/day for 48 weeks to women. The results showed decrease in Apo-B levels, and apparently also showed significant reduction in TG levels. Because the patients did not apparently include high TG levels (in excess of 500 mg/dl), Amarin argues the study did not undermine the expectation that purified EPA in patients with high TG levels would not experience a corresponding increase in LDL-C levels. Also, because the study administered EPA along with estirol, which is purportedly itself a lipid-altering agent, that did not change any expectations about the impact of pure EPA on LDL-C or Apo-B. The parties also dispute whether the study actually showed that EPA alone, rather than in combination with estirol, actually showed reduction of TG levels.
The obviousness question in this case clearly involves highly-factual scientific questions and the trial is likely to boil down to a battle of the experts. Whether or not it was “unexpected,” in light of the available prior art, that administering pure EPA to patients with high TG levels would not increase bad cholesterol, while simultaneously reducing Apo-B levels, is going to be a relatively close call. Nonetheless, there are a few obstacles that the generics will face even if they can mount a strong case of obviousness.
First, all of the primary prior art references relied upon by the generics were previously before the Examiner or discussed by the Examiner during prosecution of the patents. That, in itself, is not determinative that the district court will side with Amarin. There is precedent of courts invalidating patents based upon prior art previously considered during prosecution. Nevertheless, it does not help the generics, and adds an extra weight to their load.
Second, the burden of proving obviousness is on the generics, and it is a relatively high one. The generics must show that the patents are invalid based upon a “clear-and-convincing-evidence” standard. In short, if the case really comes down to a close call, and the court correctly applies the standard, that suggests that the court should in theory rule against invalidating the patents.
Overall, there are numerous issues in this case, and we will continue to address them in upcoming blog posts.
#EMDAC views on indication breadth - By my count, 10 members strongly in favor of approval for both secondary and primary prevention; 4 opposed for primary prevention; 2 on fence about primary
— Sue Sutter (@PinkSheetSutter) November 14, 2019
Dr. Konstam is a consultant for Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, and Novartis; and has received research support from
http://heartfailure.onlinejacc.org/content/7/11/913.abstract
https://projects.propublica.org/docdollars/doctors/print/138158
MARVIN KONSTAM
Listed Specialty: Cardiovascular Disease
750 WASHINGTON ST, NEMC BOX 836, BOSTON, MA, 02111-1526
2018 Payments: At a Glance
13
PAYMENTS
$34,168
PAYMENT TOTAL
5
COMPANIES PAID THIS DOCTOR
Types of Payments
CONSULTING
9 $33,472
TRAVEL AND LODGING
1 $593
FOOD AND BEVERAGE
3 $104
Drugs & Devices in 2018
Totals listed below account for all payments from that mention this product. Beginning in 2016, the government began classifying products as drugs, devices, biologics or medical supplies. Below, you will see drugs (drugs and biologics) and devices (devices and medical supplies). If a payment record mentions more than one product, the entire value will be included in each of those products. When no products are listed, they are not included in the list below.
PAYMENTS WITH NO LISTED PRODUCT
N/A
$19,579
VNS THERAPY
Device
$14,575
FABRAZYME
Drug
$14
† May not add up to dollar total at top of page, since a payment record may not be associated with any product or can be associated with several products.
Payment Details
All payments are displayed, the largest appearing on top.
Apr 16, 2018 $10,450 VNS THERAPY Consulting LIVANOVA USA, INC.
Jun 21, 2018 $6,847 No Listed Product Consulting TAKEDA PHARMACEUTICALS U.S.A., INC. Cardiovascular Clinical Science Foundation
May 8, 2018 $4,125 VNS THERAPY Consulting LIVANOVA USA, INC.
Mar 9, 2018 $3,850 No Listed Product Consulting AMGEN INC.
Sep 25, 2018 $3,300 No Listed Product Consulting AMGEN INC.
Oct 4, 2018 $1,750 No Listed Product Consulting IRONWOOD PHARMACEUTICALS, INC
May 2, 2018 $1,500 No Listed Product Consulting IRONWOOD PHARMACEUTICALS, INC Cardiovascular Clinical Sciences Foundation
Apr 25, 2018 $1,100 No Listed Product Consulting IRONWOOD PHARMACEUTICALS, INC
Mar 9, 2018 $593 No Listed Product Travel and Lodging AMGEN INC.
Jul 11, 2018 $550 No Listed Product Consulting IRONWOOD PHARMACEUTICALS, INC
Mar 11, 2018 $61 No Listed Product Food and Beverage AMGEN INC.
Nov 9, 2018 $28 No Listed Product Food and Beverage AMGEN INC.
May 7, 2018 $14 FABRAZYME Food and Beverage GENZYME CORPORATION
Panel live blog updated with some key slides, history, and commentary. $AMRN
— Matthew Herper (@matthewherper) November 14, 2019
Bhatt did a great job.
https://t.co/GDFTJDYeNB via @statnews
Amarin: A Look At The Briefing Docs
https://seekingalpha.com/article/4306245-amarin-look-briefing-docs
Indeed. Feel super confident now. I was thinking there would be one "gotcha" in there and I'd buy back in mid teens. Clearly this gets a favorable Adcom and PDUFA approval looking at these docs. Only slight hangover is patent case now but not concerned about that. We have quite a week ahead of us. Can only imagine what this does after positive Adcom + Evaporate + possible Euro filing. Could be $30 next week.
I played it wrong! But back in pre-market.
At end of call. Something to look forward to.
"After we get through the approval in the U.S., we’ve got a very talented R&D team who will research some of the ideas that they’ve – that they’ve halted in the past. Then we’ll come back with some communication as to what we’re going to be working on next, but right now, there is nothing larger that we could be working on than what we’re doing with Vascepa, and we want to ensure that we provide, that’s the appropriate focus. So we’ll get back to you in the future relative to what we might be working on beyond Vascepa. But Vascepa is pretty big. So let’s get that right."
This is from March 2016...
SA is hanging their hat on the sentence in Amarin PR that states:
"A separate independent, academic cost-effectiveness analysis of Vascepa based on patient-specific data from the REDUCE-IT study will be presented at the American Heart Association Scientific Sessions 2019 on November 16 by William S. Weintraub, M.D., Director of Outcomes Research, MedStar Cardiovascular Research Network. Amarin provided an unrestricted grant for this academically driven analysis, titled “Cost-Effectiveness of Icosapent Ethyl in REDUCE-IT.”
But that is NOT referring to the ICER report.
They say the analysis is "Amarin Funded"!
Ummm...no
The Institute for Clinical and Economic Review (ICER) is an independent non-profit research organization that evaluates medical evidence and convenes public deliberative bodies to help stakeholders interpret and apply evidence to improve patient outcomes and control costs. Through
all its work, ICER seeks to help create a future in which collaborative efforts to move evidence into action provide the foundation for a more effective, efficient, and just health care system. More information about ICER is available at http://www.icer-review.org.
The funding for this report comes from government grants and non-profit foundations, with the largest single funder being the Laura and John Arnold Foundation. No funding for this work comes from health insurers, pharmacy benefit managers, or life science companies. ICER receives approximately 19% of its overall revenue from these health industry organizations to run a separate Policy Summit program, with funding approximately equally split between insurers/PBMs and life science companies. Life science companies relevant to this review who participate in this program include: Janssen Pharmaceuticals, Inc. For a complete list of funders and for more information on ICER's support, please visit http://www.icer-review.org/about/support/.
Says "Abstract embargoed at this time."
Codify Our Active Moiety Approach for New Chemical Entity (NCE) Determinations
The Agency’s regulation implementing the statutory provisions on 5-year New Chemical Entity
(NCE) exclusivity focuses on evaluating a drug’s active moiety. Under this regulation,
eligibility for NCE exclusivity is available only for a drug containing no active moiety that has
been previously approved by FDA. This approach ensures that only the most innovative drugs
qualify for NCE exclusivity, while allowing for earlier generic competition for drugs that do not
qualify. A recent district court decision (Amarin Pharmaceuticals Ireland Ltd. v. FDA)
invalidated an FDA NCE exclusivity decision that applied FDA’s active moiety regulation based
on the court’s interpretation of the statute’s “plain meaning.” This decision has resulted in
uncertainty about FDA’s ability to continue to apply its regulation. This proposal would codify
FDA’s long-standing “active moiety” approach, and would provide clarity about Congress’
intent that only the most innovative new drugs qualify for NCE exclusivity.
Excellent review of Amarin's situation:
Start at about 9:00
https://breakingbiotech.com/2019/08/15/046-fda-announces-last-minute-advisory-committee-for-amarins-vascepa/
Would it be unreasonable to assume that the Vascepa arms may have elevated somewhat also if not for the effects of Vascepa?
Do people on statins perhaps become resistant somehow over time so that their numbers creep up... requiring increases in dosages?
Sorry if this comes off as clueless, as to a large degree I am! (But wanting to learn)
Would they really run a trial that "might" harm the patients taking the mineral oil? I doubt that?
I'm not saying MO would harm them but would you ever run a trial where harm is suspected?
Would you enroll in such a trial if you were on statins knowing that maybe you won't be getting the beneficial dose of statins if MO interfered with absorption?
https://www.newswire.ca/news-releases/hls-therapeutics-announces-q2-2019-financial-results-818092816.html
We believe Vascepa has the potential to transform our business and have conservatively estimated its potential peak revenue range at C$150-250 million, should it achieve regulatory approval. With its Priority Review underway, we expect to receive Health Canada's response toward the end of Q4 2019."
Here's something different:
https://www.eurekalert.org/pub_releases/2019-07/cifs-gch073019.php?fbclid=IwAR3FQM9zaDycXzfwEv0NM13B1OmP_nH24Nlyy-H01V79EOaT06ReKWzrMDU
Glowing cholesterol helps scientists fight heart disease
New research tool has the power to transform our understanding of lipoprotein biology, which will have important implications for future strategies to treat heart disease
Amarin prepared to defend patents against Epanova launch, says H.C. Wainwright After speaking with an intellectual property attorney, H.C. Wainwright analyst Andrew Fein believes Amarin (AMRN) has prepared itself to defend its patents for Vascepa against a possible launch of AstraZeneca's (AZN) omega-3 Epanova. The consultation revealed the FDA's Orange Book includes 25 patents listed for Vascepa, Fein tells investors in a research note. While, according to the IP attorney, Amarin's Orange Book patents do not appear to directly address Epanova, Amarin has a large patent portfolio in this space, says the analyst. Fein points out that Amarin could not hypothetically sue AstraZeneca for patent infringement until Epanova was made, used, or sold in a commercial context. These are not brand-generic circumstances between both companies, he writes. However, Fein thinks Amarin's patents could give it the upper hand and he reiterates a Buy rating on the shares with a $51 price target.
Read more at:
https://thefly.com/landingPageNews.php?id=2939428&headline=AMRN;AZN-Amarin-prepared-to-defend-patents-against-Epanova-launch-says-HC-Wainwright
Here it is folks:
Vascepa Set To Steal Market Share From Statins.
Source: Thailand Medical News Jun 01, 2019
Vascepa ( Icosapent Ethyl) by Amarin Group Of Companies, (New Jersey, US) is the only EPA prescription Omega-3 clinically proven to lower very high triglycerides in adults by 33%, without raising bad cholesterol (LDL-C). Unlike VASCEPA, common Omega Oil and fish oil supplements are not pure EPA and most also contain DHA which can raise bad cholesterol.
The product is already US FDA approved and in the EU but now due to new clinical trial results and studies especially its benefits in Cardiovascular Health, the US FDA is fast-tracking review of the drug’s label expansion, which analysts say will see major sales on the horizon.
The FDA put Vascepa under priority review this week, speeding what could be the first approval to reduce the risk of Cardiovascular (CV) disease in patients previously treated with statins for high LDL cholesterol with elevated persistent triglycerides. The US FDA decision deadline is set for Sept. 30, four months earlier than planned, Amarin Corporation said.
Vascepa’s strong showing in the phase 3 Reduce-It trial, data from which rolled out in September, could lead to a peak share price of $35 in the next year. Vascepa’s Reduce-It data, filed with the FDA in March, showed Vascepa lowered the risk of a major adverse CV event by 26% in previously untreated patients compared with placebo, and by 30% in statin-treated patients at a median follow-up of 4.9 years.
The general sentiment is that an (advisory committee) could be a positive for Vascepa, for example by emphasizing that (Reduce-It) is a validation of Vascepa and not of triglyceride-lowering medications.
With Vascepa on the express lane to approval, Wall Street is showing increased confidence in Amarin, with analysts increasingly impressed by the drug’s sales promise. On Wednesday, Amarin’s share prices jumped from $17.01 per share to $19.64 on the heels of the FDA news, an eye-popping 15.5% increase.
There are also speculations that an Indian Singaporean Group is extensively buying up stocks for possible board seats and control.
By the first week of May 2019, Vascepa’s total prescriptions had jumped 67.1% over the previous year, with new scripts growing by an even larger 77.8%. In a survey of 50 physicians, Doctors already favored prescribing the drug, with only 23% saying they would wait for a label expansion. That support and a label expansion could lead to a significant boost in Vascepa’s sales in 2019, potentially even taking them past Amarin’s forecast of roughly $350 million.
With everything coming up aces for Vascepa, Amarin has had to fight off challengers and charlatans over its trial results. Earlier this month, Amarin settled with two fish-oil supplement makers it claimed piggy-backed Vascepa’s trial data to promote their own products fish oil supplements. After the settlements, Amarin Corporation said it has lawyers on call, in case more supplement makers decided to take a run at the drug’s data or use any trademarks, copyrights or patents.
Medscape article. Confusing (to me anyway!) as it seemingly endorses DHA, OTC etc. in addition to EPA yet it references MESA study & REDUCE IT which studied EPA.
https://www.medscape.com/viewarticle/915674
MESA: http://heartfailure.onlinejacc.org/content/early/2019/07/03/j.jchf.2019.03.008?download=true
Higher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487)
In comments a doctor states:
Dr. Michael Mogadam 1 hour ago
This is a terrific informative study that re-affirms the cardio-protective role of long chain omega-3 PUFA. Most of the previous studies that found no CV benefits have been with low doses of about 1 gram omega-3. Other studies that measured blood levels or adipose tissue levels (on biopsy specimens) have shown that higher levels of omega-3 (both EPA and DHA) are cardio-protective.
So this study with detailed reporting of blood levels of EPA and DHA provides another rational basis to support the use of adequate doses (more than two grams per day) of omega-3PUFA. Since this would require eating several dark flesh (fatty) fish meals per week (salmon, tuna, ..), it would be quite impractical for most populations, hence we should consider very inexpensive over the counter (NOT PRESCRIPTION version) fish oil capsules.
Not all OTC fish oil capsules have adequate omega-3 PUFA or purification. For years I have recommended Nature's Bounty Fish Oil capsules, each having1400 mg total fish oil of which 647 mg is EPA and 253 mg DHA for a total of 980 mg omega-3. In the US at Costco a bottle of 130 odor-less coated softgel capsules sells for <$15, more than 10 times cheaper than the prescription version.
Seems he writes books:
https://www.amazon.com/Healthy-Breakthrough-Program-Prevent-Reverse/dp/0887235174/ref=sr_1_5?keywords=Michael+Mogadam&qid=1563377323&s=gateway&sr=8-5
Amarin’s Vascepa, AstraZeneca’s Epanova theoretical cardiovascular risk reduction class effect possibly stifled
https://www.pharmaceutical-technology.com/comment/vascepa-versus-epanova/
Although Amarin’s Vascepa (icosapent ethyl) is likely to lock in US Food and Drug Administration approval and swift uptake in cardiovascular disease (CVD) risk reduction, there could be future competition with AstraZeneca’s Epanova (omega-3-carboxylic acids).
Vascepa versus Epanova
A potential class efficacy/safety effect is possible as both therapies are approved for hypertriglyceridemia, but Epanova’s dissimilar ingredient list could be a key differentiating element.
Potential differentiation lies with the fact that Vascepa features omega-3 fatty acid eicosapentaenoic acid (EPA), whereas Epanova contains both EPA and docosahexaenoic acid (DHA). There is limited data supporting DHA’s clinical value. DHA could be an efficacy burden as it may impede Epanova in delivering cholesterol and inflammation reductions that are potentially vital for CVD reduction.
However, these differences may be inconsequential if the ongoing Phase III STRENGTH trial (NCT02104817) investigating Epanova matches Vascepa’s positive Phase III REDUCE-IT (NCT01492361) data since it is still unclear how Vascepa’s mechanism is able to deliver positive results. One potential way to find differentiating elements is via posthoc analysis of both Phase III trials, they added said. The 13,086-patient, double-blind, placebo-controlled STRENGTH trial is expected to complete in October 2019 (Nicholls, SJ, et. al, Clin Cardiol. 2018 Oct;41(10):1281–1288).
Nonetheless, if both therapies have comparable efficacy, DHA could still cause more gastrointestinal-related side effects, and Epanova’s potential improved absorption edge may lack real-world value.
Meanwhile, Vascepa’s approval in CVD risk reduction is supported by positive REDUCE-IT data. Uptake will likely be swift, and barriers may be imposed on competing hypertriglyceridemia therapies for off-label use in CVD risk reduction.
Vascepa has a Prescription Drug User Fee Act date of January 2020. Analysts forecast Vascepa will have $1.1 billion peak sales in 2027. Epanova’s estimated launch date has yet to be announced. Amarin has a market capitalisation of $5.8billion, while AstraZeneca’s is $77.1billion.
Class effect possible but DHA could be a key differentiator
A class effect between Vascepa and Epanova in the reduction of CVD risk is possible, according to Jane Armitage, professor, clinical trials and epidemiology at the UK’s University of Oxford, Dr Evan Stein, chief scientific officer at the Medpace Metabolic & Atherosclerosis Research Center, Chicago, Illinois and Dr Eliot Brinton, REDUCE-IT investigator and president at Utah Lipid Center, Salt Lake City.
Vascepa was US Food and Drug Administration-approved for the reduction of triglyceride levels in patients with 500mg/dL or more in July 2012, and Epanova was approved in the same indication in May 2014.
As such, these therapies’ success in CVD risk reduction could come down to marketing, said Stein and Dr Paul Thompson, medicine professor of preventative cardiology at UConn Health, Farmington, Connecticut, US. Vascepa may be at a disadvantage as it comes from a relatively smaller company, noted Dr Kosh Ray, honorary consultant cardiologist at Imperial College NHS Trust, London, UK.
Epanova contains the omega-3 fatty acids EPA and DHA. DHA may have more pronounced positive effects on vascular reactivity, and could be of clinical importance for patients with high CVD risk, an AstraZeneca spokesperson noted. Currently, 1g of generic EPA plus DHA is prescribed for secondary prevention after a heart attack, so there is the possibility of a dose-related efficacy boost with Epanova 4g being investigated in the STRENGTH trial, Armitage noted.
However, it is still unclear if the addition of DHA is valuable in CVD risk reduction due to the lack of any meaningful clinically related data, Brinton said. As per its FDA label, Epanova’s effect on cardiovascular mortality and morbidity has not yet been determined. In the 18,645-patient Phase IV JELIS trial (NCT00231738), the addition of EPA to statins was shown to provide added benefit in preventing coronary events, Thompson noted, adding comparable data is not present with DHA. JELIS data shows 262 (2.8%) EPA patients had a major coronary event with a mean 4.6-year follow-up, versus 324 patients (3.5%) in the control group (p=0.011) (Yokoyama, M, et. al, Lancet. 2007 Mar 31;369(9567):1090–1098).
DHA draws further reservations for a class effect, as it has the tendency to raise high-density lipoprotein cholesterol (HDL-C), Brinton said. DHA is also not as efficacious in reducing low-density lipoprotein cholesterol (LDL-C), Thompson and Amarin CEO John Thero added. This due to DHA’s weaker impact on cellular receptors, Brinton said. DHA also seems to enhance the likelihood of creating cholesterol crystals, Brinton added.
Additionally, DHA is not as efficacious with regards to easing inflammation in the body based on studies using the C-reactive protein blood test, Brinton noted. This could be crucial, as there seems that other mechanism elements led to the positive REDUCE-IT data, including reducing inflammation, said Amarin’s Thero and REDUCE-IT investigator Dr Michael Miller, professor of cardiovascular medicine at the University of Maryland School of Medicine, Baltimore, Maryland, US.
Vascepa mechanism still unclear
However, these differences could be inconsequential if the STRENGTH trial matches the REDUCE-IT data, Stein said. The STRENGTH trial data would clarify the clinical relevance of these differences, Thompson and Miller noted. It is still unclear how Vascepa’s mechanism was able to deliver positive REDUCE-IT results, Thompson and Ray said.
REDUCE-IT results do not seem to be linked to reducing triglyceride levels alone since reduction by Vascepa is modest, Thompson said. Vascepa was approved in hypertriglyceridemia based on its triglyceride 27% reduction from baseline, versus 10% in placebo, an FDA press release shows. To see such CVD risk reduction results, LDL-C reduction with Vascepa should have been notable, but it was not, Stein said.
One way to find any differentiating elements would be in posthoc analysis of Phase III data, as comparing these trials directly may be inappropriate due to trial design nuances, Stein added. For example, in REDUCE-IT, there seemed to be greater benefit in patients under the age of 65 years with Vascepa, said Brinton, adding this age frame could be worth exploring once Epanova’s own results come out.
However, Armitage noted this age-based differentiation may be superficial. More clinical assessments in the study protocol were conducted on the younger patients, which can lead to the perception of greater benefit in this patient cohort, she added. REDUCE-IT enrolled patients ages 45 years and older.
If both therapies have comparable efficacy profiles, Epanova’s DHA could be relevant regarding side effects, Brinton said. Epanova seems to have more gastrointestinal side effects due to free fatty acid present in the intestine, he added. The most common Epanova side effects include diarrhoea, upset stomach, abdominal pain and discomfort, and Vascepa’s most common side effect being joint pain, according to their respective FDA labels.
Epanova’s advantage is that it could provide better absorption, so it has a potential convenience edge, the AstraZeneca spokesperson, Stein and Brinton said. REDUCE-IT patients were dosed at 2g twice daily, while STRENGTH patients are dosed at 4g once daily. However, this has little real-world value as better absorption may only be noticeable after a 12-hour fast, Brinton said.
Vascepa approval likely, leading to positive uptake
Nonetheless, all experts agreed the REDUCE-IT data are promising for FDA approval. A total of 17.2% of Vascepa patients experienced the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization or unstable angina, versus 22% in the placebo group (p<0.001) (Bhatt, D. et. al, N Engl J Med 2019; 380:11–22).
This is impressive considering it has always been challenging to show CVD event reduction on top of statins, as demonstrated by many failed trials, Thompson said. PCSK9-based therapies have only been able to show 15% CVD risk reduction, Stein added.
The aforementioned nebulous Vascepa mechanism in CVD risk reduction is unlikely to be an FDA approval obstacle since there are many therapies in other indications that have been approved with unclear mechanisms, Thompson and Stein said. Vascepa has a positive side-effect profile that supports approval, Stein added.
While Vascepa has some bleeding side effects, this could be a sign for a potential impact to prevent clotting, Stein noted. The reported atrial fibrillation could be a class effect as this has also been reported with GlaxoSmithKline’s Lovaza (omega-3-acid ethyl esters), which is also approved for hypertriglyceridemia, Brinton said.
Once approved, Vascepa will be embraced by clinicians, Thompson said. Payers may establish reimbursement and prior authorisation barriers, Miller said, adding payers are also likely to relent due to positive REDUCE-IT results. Educating clinicians could be a challenge since the market is large and has had limited innovation beyond available cholesterol management, Amarin’s Thero said.
by Reynald Castaneda in London
Reynald Castaneda is a Senior Reporter for Pharmaceutical Technology parent company GlobalData’s investigative journalism team. A version of this article originally appeared on the Insights module of GlobalData’s Pharmaceutical Intelligence Center. To access more articles like this, visit GlobalData
https://www.acc.org/latest-in-cardiology/articles/2019/06/05/07/40/eagles-eye-view-03june2019/?utm_medium=social&utm_source=twitter_post&utm_campaign=twitter_post
Starts at 55 seconds....
"Very impressive trial"
No, that's just the address of the domain proxy company.
Medical Research Collaborative, LLC
https://www.whois.com/whois/medicalresearchcollaborative.com
Registered On:2019-03-22
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Product Code: AMRN Report
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"Furthermore, the subject matter entailing our focus can at times be controversial, and the publication of reports on such result in the provocation of ad hominem attacks that distract from the work itself. Also, a truly zealous antagonist that misconstrues he has been harmed by our reports could even in some instances jeopardize the careers of certain members of the Collaborative by harassing the establishments at which they work (not to mention their family members). It would be different if our chosen path was journalism, as journalists revel in controversy--but it was not. For these reasons, the identities of the members of Medical Research Collaborative, LLC shall remain anonymous. "
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Give me a break!
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8:29 AM - 29 May 2019
$AMRN operational execution has been flawless. Since last year, John Thero has offered a master class in the CEO art of underpromising and overdelivering.
— Adam Feuerstein ✡️ (@adamfeuerstein) May 29, 2019