Epanova (eicosapentaenoic acid/docosahexaenoic acid) / AstraZeneca - LARVOL DELTA

Pemafibrate and other triglyceride-lowering therapies to reduce risk of cardiovascular and metabolic disease. (PubMed, Curr Opin Cardiol) - "Taken together, HTG is associated with increased risk of CVD and attendant adverse metabolic sequalae. To this end, a potentially promising and evidence-based landscape is emerging for treating a clinical phenotype that in the past has been insufficiently addressed."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Myocardial Infarction • Pancreatitis

Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study. (PubMed, J Atheroscler Thromb) - "The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hypertriglyceridemia

"Actually he did the STRENGTH trial of Epanova which was a mixture. Vascepa has been studied in JELIS, CHERRY, NISHIO, NOSAKA, and RESPECT-EPA ALL positive." (@neeche41)

"My goodness, doctor! Do you still not understand the difference between VASCEPA (pure EPA) & EPANOVA (DHA & EPA)?" (@ra_fun)

"Stop it Steven it is obvious you are still jaded over the failed Epanova Strength study. $AMRN #Vascepa @Amarincorp" (@SirJoke5)

Study Protocol and Baseline Characteristics of Randomized Trial for Evaluating Secondary Prevention Efficacy of Combination Therapy-Statin and Eicosapentaenoic Acid: RESPECT-EPA, The Combination of a Randomized Control Trial and an Observational Biomarker Study. (PubMed, Am Heart J) - "After this study is completed, we will have further evidence on whether a highly purified EPA is effective in reducing cardiovascular events for secondary prevention or not, as well as whether if EPA/AA ratio is a predictor for future cardiovascular events."

Biomarker • Combination therapy • Journal • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Ischemic stroke • Metabolic Disorders • Myocardial Infarction

The 2021 Marine Pharmacology and Pharmaceuticals Pipeline. (PubMed, FASEB J) - "In 2021, new marine-derived drugs were approved by FDA, as well as in Australia and China. The clinical development of marine-derived drugs remained very robust and active with several advancing to Ph III, Ph II and entering at Ph I."

Journal • Dyslipidemia • Herpes Simplex • Hypertriglyceridemia • Oncology • Pain

"AstraZeneca to discontinue Epanova trial, expects $100 million writedown https://t.co/UJLmGENf5h" (@CMichaelGibson)

HEPANOVA: A phase II trial of tumor treating fields concomitant with sorafenib for advanced hepatocellular carcinoma (AACR 2018) - "Sample size was calculated using an Exact test for proportions considering the weighted average of ORR of patients who had either complete or partial response per RECIST criteria in historical studies with sorafenib is 4.5%. A sample size of 25 patients was required to achieve a power of approximately 80% at a one-sided alpha level of 0.05 using a single sample Exact test for proportions."

P2 data • Hepatocellular Cancer

A possible explanation for the contrasting results of REDUCE-IT vs. STRENGTH: cohort study mimicking trial designs. (PubMed, Eur Heart J) - "The contrasting results of REDUCE-IT vs. STRENGTH can partly be explained by a difference in the effect of comparator oils (mineral vs. corn), but not of active oils [eicosapentaenoic acid (EPA) vs. EPA + docosahexaenoic acid], on lipid traits and C-reactive protein. The unexplained additional 13% risk reduction in REDUCE-IT likely is through other effects of EPA or mineral oil."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Immunology • Inflammation • CRP

Update on the omega-3 fatty acid trial landscape: A narrative review with implications for primary prevention. (PubMed, J Clin Lipidol) - "Two recent trials of mixed formulations - STRENGTH (Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) and OMEMI (Omega-3 fatty acids in Elderly patients with Myocardial Infarction) - studied contemporarily treated patients with mixed EPA + DHA formulations at higher doses than before and showed no benefit, thus adding valuable information to our overall understanding of this evolving therapeutic class. In this review, we contextualize the findings of STRENGTH and OMEMI within the existing omega-3 FA clinical trial landscape and look ahead to how future trials can inform existing knowledge gaps, particularly with regards to the applicability of these agents within the primary prevention realm."

Journal • Review • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Myocardial Infarction

How STRENGTH Results Impact REDUCE-IT, with Deepak Bhatt, MD, MPH (Practical Cardiology) - "As part of our coverage of ACC.21, Practical Cardiology reached out to Deepak Bhatt, MD, MPH, to learn about his reaction to the latest analysis of the STRENGTH trial and how it might impact how REDUCE-IT results are interpreted....The analysis also revealed use of the agent was associated with an increased risk of new onset atrial fibrillation, which Nissen noted is not the first study examining a fish oil-based therapy to reach this conclusion."

Video

New STRENGTH Analysis Revives Omega-3 Debate (TCTMD) - "Deepak Bhatt...principal investigator of REDUCE-IT, who was the discussant following Nissen’s presentation, had another theory: 'Alternatively, it could just be different drug, different results.'"

Media quote

Icosapent ethyl: scientific and legal controversies. (PubMed, Open Heart) - "The story of the development of icosapent ethyl has been fraught with challenges, including the invalidation of six core patents on the product, and recently, the completion of a new clinical trial, STRENGTH (Long-Term Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia), that directly contradicts REDUCE-IT and calls into question whether icosapent ethyl is actually effective in the secondary prevention of cardiovascular events. This article traces the course of the development of this fascinating product and discusses its complex medical, regulatory and legal history, which is still continuing to unfold."

Journal • Review • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders

The clinical black, white, and gray lessons. (PubMed, Curr Opin Lipidol) - "A comprehensive review revealed many differences between the trials, which could have contributed to observed divergent results. Consistent findings across multiple trials help strengthen the evidence for specific endpoints or sub-populations, and these findings must be included in guidelines. Large prospective cohort studies with diligent study protocols are warranted in the future to resolve unanswered dilemmas."

Clinical • Journal • Acute Coronary Syndrome • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hypertriglyceridemia

"Clearly libelous to insert a Vascepa capsule and not even mention Epanova." (@louieblouie1)

"Acquiring $AMRN after the EPANOVA disaster? Afterall, the EU version of Vascepa is named vAZkepa. 🙃" (@MnbioMike)

Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease risk: current status and treatments. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "The current management of elevated triglyceride levels and the effect on cardiovascular outcomes is an emerging area of research. New data from fish oil studies suggest differences in EPA vs. EPA/docosahexaenoic acid cardio protection outcomes. The preliminary data from ongoing clinical trials of novel triglyceride-lowering therapeutics are promising. These programs will ultimately provide foundations for future triglyceride-lowering guidelines."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Myocardial Infarction

[VIRTUAL] Marine pharmacology and the marine pharmaceuticals pipeline in 2020 (ASHP 2020) - " In September 2020, the clinical marine pharmaceutical pipeline consisted of 14 marine-derived drugs approved by the United States Food and Drug Administration (FDA) and 1 approved in Australia: for cancer, cytarabine (Cytosar-U, Depocyt, FDA-approved 1969); for Herpes Simplex Virus, vidarabine (Vira-A, FDA-approved 1976); for pain, ziconotide (Prialt, FDA-approved 2004); for hypertriglyceridemia, omega-3-acid ethyl esters (Lovaza, FDA-approved 2004, Vascepa, FDA-approved 2012, Epanova, FDA-approved 2014); for cancer, eribulin mesylate (Halaven, FDA-approved 2010), brentuximab vedotin (Adcetris, FDA-approved 2011), trabectedin (Yondelis, FDA-approved 2015), Plitidepsin (Aplidine, approved in Australia 2018), polatuzumab vedotin (Polivy, FDA-approved 2019), enfortumab vedotin-ejfv (PACDEV, FDA-approved 2019), lurbinectedin (Zepzelca, FDA-approved 2020), belantamab mafodotin-blmf (Blenrep, FDA-approved 2020). It is important to note that the global preclinical marine..."

Dyslipidemia • Herpes Simplex • Hypertriglyceridemia • Oncology • Pain

"How come there is never a mention of the 25% incidence of gastrointestinal distress in the Epanova population in the strength trial? Maybe compliance was another factor." (@hedgiesinvest)

Clinical • Gastrointestinal Disorder

"L’#Epanova (@AstraZeneca), Omega-3 CA, est un composé d’acide carboxylique d’#EPA et de #DHA qui ne nécessite pas d’hydrolyse par une lipase pancréatique et a donc, comparé aux formulations habituelles d’oméga-3, une meilleure disponibilité." (@pierreperochon)

Cleveland Clinic-Led Trial Finds High Doses of a Prescription Fish Oil Do Not Reduce Major Cardiac Events in High-Risk Patients (Cleveland Clinic) - "'These results have prompted the question of why the STRENGTH trial was neutral while a previous trial was favorable,' said Steven Nissen...'These results suggest that a review of the entire class of fish oil products is warranted to determine what labeling changes might be appropriate for these products, including whether high-dose fish oil supplements truly provide benefits given the risk of atrial fibrillation,' Dr. Nissen said. 'These results also have implications for over-the-counter fish oil since many patients take large doses to avoid the expense of prescription drugs.'"

Media quote

Deepak Bhatt, MD: STRENGTH, REDUCE-IT, and DHA (Practical Cardiology) - "Deepak Bhatt, MD, MPH, offers his thoughts on the most important REDUCE-IT analyses released in 2020 and why he disagrees with the notion results of the STRENGTH trial somehow impact the use of icosapent ethyl in clinical settings."

Video

"#Evinacumab #Omemi #Epanova vidéo on https://t.co/zxbmeWAOX3 which summarizes the key points at #AHA2020" (@SABOURETCardio)

"is it rather: different substance (Epanova), so different results? https://t.co/DASveOF3iF" (@tomorrowdaworld)