Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Omega-3 polyunsaturated fatty acids impinge on CD4+ T cell motility and adipose tissue distribution via direct and lipid mediator-dependent effects.
https://www.ncbi.nlm.nih.gov/pubmed/31399738
Vascepa found beneficial to Mom - EPA decreases placental lipid deposition and improves placental oxidative stress homeostasis independent of SIRT1.
https://www.ncbi.nlm.nih.gov/pubmed/31408587
Conclusion
Statin-treated patients with TG levels of 150 mg/dL or greater had worse CV and health economic outcomes than those with well-managed TG (<150 mg/dL) and HDL-C (>40 mg/dL) levels.
https://www.sciencedirect.com/science/article/pii/S0025619619303829
Vascepa MOA eludicated: Eicosapentaenoic Acid (Epa) Inhibits Human Low-Density Lipoprotein Oxidation In A Concentration- And Time-Dependent Manner At Pharmacologic Doses In Vitro
https://www.atherosclerosis-journal.com/article/S0021-9150(19)30687-2/abstract
BB, an interesting idea. So FDA was using threat of Adcom to have Amarin back off label demands. That could explain why FDA asked Amarin to avoid disclosing to investors. Instead, Amarin called their bluff and announced the Adcom as a final decision taking the leverage away from FDA.
Imagine a new PR in a week or so... FDA announces no Adcom
They can do whatever they want, anytime.
Raf, completely agree. It’s 2013 all over again
FDA and Amarin are at war
Will, we’ve been there done that. Here is a website from the 2013 saga (that continues to plague Amarin and stakeholders
Poke around, you’ll find a wealth of info
http://epadruginitiative.com
Marzan, WRONG!
Light paraffin oil = mineral oil
https://www.sciencedirect.com/topics/engineering/paraffin-oil
FFS “Amarin should go nuclear”
They already have
FDA approved drug
ADA SOC
1st Amendment rights to speak on R-I
$400M cash
Sales force
Re the raise - It was prudent to add $400M+ to the war chest for several reasons
1)While we all agree FDA approval is considered “in the bag”, the fact is that nothing is 100% certain, and is especially true with matters concerning FDA. As we see. Amarin is not sitting still and is taking on anyone who is trying to take them down. They are fighting with a vengeance - to protect your investment thesis! Why leave anything to chance? What If FDA becomes befuddled by MO issue, and extends approval date to sort out or issues a CRL for 6 month MO study? With these jokers anything is possible.
2) A big war chest improves negotiating leverage with partners, etc.
3) Reps are a costly necessity, at least for foreseeable future. AMRN would not hire 400 more Reps if V sold itself (as some contend). Uptake resistance comes from mind-share with other CVD related drugs, education and endless stream of Reps - all vying for Docs attention.
4) Docs don’t change SOC easily. It takes a while for a new drug or treatment to take hold. How many Docs remain confused about Fish Oil Supplements, and/or don’t know about Vascepa ? Plenty
Sanofi had 2,000 reps selling its PCSK9 drugs. Reps are a requirement for Rx growth pure and simple. AMRN needs to spend money educating Docs
5) Consumer education - Amarin is producing commercials right now. These will start educating the public of residual risk remaining after optimal Statin therapy. This is brilliant. “Make them sick, then offer a solution” This will be a turbo charger on demand and cause Docs to learn about V and it’s MOA
Nobody likes dilution but the global opportunity is huge - perhaps the largest of any single drug - ever. That is a threat to BP because as V takes mind share, it takes away Rx spend from other drugs. And because of that, a large war chest is warranted - global war is breaking out and Amarin has a very large target painted on its back.
Be thankful their war chest is full
Last year, the World Economic Forum reported almost 90% of the Earth's fish reserves were either fully exploited, overexploited, or depleted. Alyssa Plese, a member of UC Berkeley's Alternative Meats Lab, is confident plant-based fish could be the solution to the overfishing epidemic.
“Current evidence supports the finding that omega-3 PUFAs with EPA?≥?60% at a dosage of ≤1?g/d would have beneficial effects on depression. “
ncbi.nlm.nih.gov/pubmed/31383846
Introduction
Chronic kidney disease (CKD) is a common disease worldwide. A large portion of cases eventually develop end-stage kidney failure, a damaging condition that demands lifelong dialysis or kidney transplantation [1]. A better understanding of the cellular and molecular mechanisms of renal EMT and fibrosis is helpful for developing effective strategies for CKD treat-
ment.
Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, derived from fish oil, was beneficial for inflammatory and oxidative mechanisms involved in atherosclerotic plaque formation and progression [2]. A previous study revealed that the efficacy of polyunsaturated fatty acids, such as EPA and docosahexaenoic acid (DHA), on IgA nephropathy patients with proteinuria depended on the dose and size [3]. EPA inhibited the early progression of tubulointerstitial injury in Thy-1 nephritis models, and the inhibitory effect was related to its regulation of I?Ba [4].
MicroRNAs (miRNAs) comprise a large group of regulatory RNAs with length ~22 nucleotides
EPA attenuates epithelial-mesenchymal transition and fibrosis through the TGF-ß1/Smad3/ILK pathway in renal tubular epithelial HK-2 cells by up-regulating miR-541
https://www.dropbox.com/s/ifrzbjhpvd3rb2u/ijcep0090924.pdf?dl=0
It’s a shot across the bow
Tasty, GS saw the tumultuous markets coming that we’re seeing today and advised accordingly.
The raise is behind us, they have all the cash needed to grow to multi- billions/ yr. It was a smart move. You raise money when you don’t need it. Much harder to raise when you do.
The trade war is being ratcheted up. China won’t fold
?Conclusions:?
?Administered EPA tends to be incorporated from the vascular lumen side and preferentially taken into the thin-cap plaque.?
?More elucidation of Vascepa pleiotropic MOA
?https://www.ahajournals.org/doi/abs/10.1161/ATVBAHA.119.313093?af=R&?
bird, makes sense to me V will be larger than Lipitor - the label will be CVD prevention by being added to each of the following. These compete with each other. For now, Vascepa has no competition
atorvastatin (Lipitor)
fluvastatin (Lescol)
lovastatin (Mevacor, Altocor)
pravastatin (Pravachol)
pitavastatin (Livalo)
simvastatin (Zocor)
rosuvastatin (Crestor)
patent app: Statin dose delivered on the surface of Vascepa
https://www.dropbox.com/s/y5x470b0zd75jkw/16193131%20new%20combo%20patent%20published.pdf?dl=0
another patent app: method of preventing or reducing oxidation of HDL in subject at risk for CVD
https://www.dropbox.com/s/g4cyxrlpzi7ovrc/15998570%20method%20of%20preventing%20or%20reducing%20oxidation%20of%20HDL%20in%20subject%20at%20risk%20for%20CVD.pdf?dl=0
Another nice SE
https://www.ncbi.nlm.nih.gov/pubmed/31349710
Effect of Rosuvastatin and Eicosapentaenoic Acid on Neoatherosclerosis
https://www.ncbi.nlm.nih.gov/pubmed/31334703
The summary estimate showed that EPA intervention significantly reduced systolic blood pressure (SBP) (-2.6?mmHg; 95%confident interval (CI): -4.6, -0.5?mmHg), especially in subjects with dyslipidemia (-3.8?mmHg; 95%CI: -6.7, -0.8?mmHg). The pooled effect indicated that supplemental DHA exerted a significant reduction in diastolic blood pressure (DBP) in subjects with dyslipidemia (-3.1?mmHg; 95%CI: -5.9, -0.2?mmHg). Both EPA (-0.56?mg/L; 95%CI: -1.13, 0.00) and DHA (-0.5?mg/L; 95%CI: -1.0, -0.03) significantly reduced the concentrations of C-reactive protein (CRP), respectively, especially in subjects with dyslipidemia and higher baseline CRP concentrations. Given that limited trials have focused on EPA or DHA intervention on concentrations of interleukin (IL)-6 and tumor necrosis factor (TNF)-a, further RCTs should be explored on these inflammatory factors. The present meta-analysis provides substantial evidence that EPA and DHA have independent (blood pressure) and shared (CRP concentration) effects on risk factors of chronic diseases, and high-quality RCTs with multi-center and large simple-size should be performed to confirm the present findings.
https://www.ncbi.nlm.nih.gov/pubmed/29993265
Docosahexaenoic acid reduces resting blood pressure but increases muscle sympathetic outflow compared with eicosapentaenoic acid in healthy men and women.
Abstract
Supplementation with monounsaturated or ?-3 polyunsaturated fatty acids ( n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and the mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-wk, randomized, double-blind trial examining the effects of orally supplementing ~3 g/day of EPA ( n = 28), DHA ( n = 28), or OO ( n = 30) on resting hemodynamics; MSNA was examined in a subset of participants ( n = 31). Both EPA and DHA supplements increased the ?-3 index ( P < 0.01). Reductions in systolic BP were greater [adjusted intergroup mean difference (95% confidence interval)] after DHA [-3.4 mmHg (-0.9, -5.9), P = 0.008] and OO [-3.0 mmHg (-0.5, -5.4), P = 0.01] compared with EPA, with no difference between DHA and OO ( P = 0.74). Reductions in diastolic BP were greater following DHA [-3.4 mmHg (-1.3,-5.6), P = 0.002] and OO [-2.2 mmHg (0.08,-4.3), P = 0.04] compared with EPA. EPA increased heart rate compared with DHA [4.2 beats/min (-0.009, 8.4), P = 0.05] and OO [4.2 beats/min, (0.08, 8.3), P = 0.04]. MSNA burst frequency was higher after DHA [4 bursts/min (0.5, 8.3), P = 0.02] but not OO [-3 bursts/min (-6, 0.6), P = 0.2] compared with EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA, but not OO, increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic overactivation. NEW & NOTEWORTHY We studied the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and olive oil supplementation on blood pressure (BP) and muscle sympathetic nerve activity (MSNA). After 12 wk of 3 g/day supplementation, DHA and olive oil were associated with lower resting systolic and diastolic BPs than EPA. However, DHA increased MSNA compared with EPA. The reductions in BP with DHA likely occur via a vascular mechanism and evoke a baroreflex-mediated increase in sympathetic activity.
https://www.ncbi.nlm.nih.gov/pubmed/30735073
So Kiwi bullish and Tony terrified? Really?
the world is tipsy turvy - oh well
Sonam,
They have patent apps for combo with almost every cardio drug. I dont recall one specifically for pitavastatin, but I recall seeing one that lists several statins. They also have apps for co-administration of statins and to your question on the size of pill, I've seen apps describing statin sprayed on Vascepa - 4 V pills contain a lot of surface area
The other more important point is less about compliance (although key) rather it is about pharmacological studies showing the clearance of hydroperoxides being accelerated by the combined statin and V. This behavior has been known by Amarin for some time but it wasn't until R-I that USPTO recognized the findings as being novel, unexpected enough to grant a patent.
I can see more studies which elucidate the combined effects which will help reveal MOA that causal to R-I results
Zip, good points, and I agree.
BTW they already have the same IP granted in Europe. Perhaps the recent raise includes funding for some development of AMR102
significant IP milestone on 7/19
AMRN granted new patent: PHARMACEUTICAL COMPOSITION COMPRISING OMEGA-3 FATTY ACID AND HYDROXY-DERIVATIVE OF A STATIN AND METHODS OF USING SAME.
https://www.dropbox.com/s/jzxjixkdavtw92e/14729615%20Allowance.pdf?dl=0
Omega-3 Fatty Acids Survey in Men under Active Surveillance for Prostate Cancer: from Intake to Prostate Tissue Level.
Moussa H1, Nguile-Makao M1, Robitaille K1, Guertin MH1, Allaire J2, Pelletier JF1, Moreel X1,3, Gevariya N1, Diorio C1, Desmeules P3,4, Têtu B1,4, Lamarche B2, Julien P5, Fradet V6,7.
Author information
Abstract
Dietary omega-3 fatty acids (?3), particularly long-chain ?3 (LC?3), have protective effects against prostate cancer (PCa) in experimental studies. Observational studies are conflicting, possibly because of the biomarker used. This study aimed at evaluating associations between grade reclassification and ?3 levels assessed in prostatic tissue, red blood cells (RBC), and diet. We conducted a validation cross-sectional study nested within a phase II clinical trial. We identified 157 men diagnosed with low-risk PCa who underwent a first active surveillance repeat prostate biopsy session. Fatty acid (FA) intake was assessed using a food frequency questionnaire and their levels measured in prostate tissue and RBC. Associations were evaluated using logistic regression. At first repeat biopsy session, 39 (25%) men had high-grade PCa (grade group ≥2). We found that high LC?3-eicosapentaenoic acid (EPA) level in prostate tissue (odds ratio (OR) 0.25; 95% (confidence interval (CI) 0.08-0.79; p-trend = 0.03) was associated with lower odds of high-grade PCa. Similar results were observed for LC?3 dietary intake (OR 0.30; 95% CI 0.11-0.83; p-trend = 0.02) but no association for RBC. LC?3-EPA levels in the target prostate tissue are inversely associated with high-grade PCa in men with low-risk PCa, supporting that prostate tissue FA, but not RBC FA, is a reliable biomarker of PCa risk.
Icosapent Ethyl Reduces Atherogenic Markers in High-Risk Statin-Treated Patients With Stage 3 Chronic Kidney Disease and High Triglycerides.
https://www.ncbi.nlm.nih.gov/pubmed/31306043
Excellent (new) lecture but Dr Mason on biologics of EPA
Reviews causal factors of CVD, inflammation, oxidized lipoprotein, crystalline domains, plaque etc.
Role of EPA to stop inflammation, interfere with creation of Crystalline domains vs DHA in membrane
The remarkable synergy of EPA with Statins in clearance of poisonous hydro peroxide, and resulting reduction of oxidized LDL-C and oxidized HDL.
Explains reason supplements are dangerous and actually worsen CVD
https://reachmd.com/programs/video-library/biologic-basis-epa-reduce-atherosclerosis-burden/10541/
Conclusions: Our findings suggest that AA status may impact depression pathophysiology through effects on serotonin transport. Future studies should examine whether these relationships explain the therapeutic effects of PUFAs in the treatment of MDD.
https://www.sciencedirect.com/science/article/abs/pii/S0165032718330751
DHA does not convert to EPA. EPA converts to DHA
https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqz097/5519526?redirectedFrom=fulltext
Thanks Zip, I know you have direct experience. Moving the flywheel on Vascepa adoption will take human energy. If Amarin could each its sales goals without reps, it would.
Makes sense...
?CONCLUSION:?
??-3 epoxy products from ?-3 PUFA metabolism play a crucial role in inhibiting pancreatic cancer growth, and use of ?-3 PUFAs combined with sEH inhibition is a strategy with high potential for pancreatic cancer treatment and prevention?
?https://www.ncbi.nlm.nih.gov/pubmed/31262891?
“D) is Dr Bhatt going to pull something unforeseen with the RI data? “
Interesting point, as my Twitter interactions with Dr. Byatt on the topic separation of arms revealed his conviction the R-I data as is, understates the RRR and Risk Reduction continues to increase past 4.5 yrs
I’m not exactly sure how, but I would not be surprised if Dr. Bhatt figures out how to produce data that shows the separation trajectory continues and RRR increases with use past 4.5 years. Now that would be interesting.
Sales Reps
Besides the obvious detailing, reps dog the Docs until they “see the light”. But despite stellar results There’s a lot of competition for mind share. Drugs for blood pressure, thinners, diabetes, A-Fib.. on and on. Even if Docs agree with findings, they may see the Vascepa patient profile far narrower than we do. It’s simply not easy as some here would have you believe.
For those who think reps aren’t needed, it’s because we expect Docs to think like us. opinions are biased because of personal conviction. Docs are inherently conservative. Not all, but surely most are and it takes several attempts to get the Doc to begin adoption.
Need proof? If reps were not needed, we’d be doing double the weekly scripts we are.
KOLs are also needed, but organizing talks, speakers and events, is tedious and time consuming work done by reps.
Finally, when a doc goes “all in” and elects to move his SOC using Vascepa, it’s not done as a Big Bang. They move one patient at a time and often times the Doc refers the migration to occur with the rep and office manager working in tandem. Then we have insurance coverage issues.
It would be be great to sell V like a consumer product but it’s not happening it’s not happening.
JT knows what to do