•Every 33 seconds someone in the United States dies from cardiovascular disease, which is roughly the equivalent of a September 11th-like tragedy repeating itself every 24 hours, 365 days a year.
•More Americans die of heart disease than of AIDS and all cancers combined.
•In 2013, more than 920,000 Americans will have experienced a heart attack, nearly half of them occurring without prior symptoms or warning signs.
•250,000 Americans (680 every day of the year) die annually of Sudden Cardiac Death.
•One-half of the victims of Sudden Cardiac Death are under the age of 65.
•An estimated 80 million Americans have one or more types of heart disease.
•Each year, about 8.9 million Americans have chest pain (angina) caused by reduced blood flow to the heart muscle, which occurs when the coronary arteries become blocked with a build-up of plaque.
•While the cost in terms of human suffering is incalculable, in 2008, the total financial cost of cardiovascular disease (coronary heart disease, hypertensive disease, heart failure and stroke) in the U.S. was estimated at $448.5 billion (this includes direct costs such as costs of doctors, hospital services, medications, etc., and indirect costs such as lost productivity). In comparison, the estimated economic cost of cancer in 2007 was $219 billion.
The American Heart Association acknowledges that the amount of triglycerides (or blood fats) in the blood is an important indicator of metabolic health; high TG levels are associated with coronary heart disease, diabetes and fatty liver disease.
Vascepa has demonstrated a remarkable efficacy in lowering TG levels. In ANCHOR, the largest trial ever conducted of an Omega-3 therapy in patients with high TGs on background statin therapy, a 4-gram dose of Vascepa was shown to reduce TG levels by over 21% (p 6% was also achieved. (con'd below)
•The FDA completely ignored subgroup analyses from these trials, which showed that patients •The FDA completely ignored subgroup analyses from these trials, which showed that patients with high TG and low HDL had a reduction in CVD risk of 28% and 37% in ACCORD-Lipid and AIM HIGH, respectively.
•Ironically, analyses of the data from these subgroups support Vascepa’s approval for high TGs based on the effectiveness of these other TG lowering agents in achieving robust CVD risk reduction outcomes for patients already on background statin therapy. This is exactly the ANCHOR population.
The Agency has the opportunity to re-evaluate the data from these studies under the appeal currently underway.
A second key principle of SMG9001.1, “Shielding the Agencyʼs science and its scientific staff from political influence”, should be taken into account relative to the competitive landscape for Vascepa’s parent company, Amarin Corp. Amarin is a much smaller company than the large pharmaceutical companies whose drugs would compete with Vascepa. Large pharmaceutical companies are constantly accused of attempting to influence FDA decision-making. EPADI hopes this has not occurred during the FDA’s review of Vascepa and urges senior Agency officials to be sure this policy has indeed been vigorously enforced.
We contend that denying patients on background statin therapy theproven and safe TG and LDL-C lowering effects of Vascepa makes absolutely no sense given the epidemic nature of heart disease, the associated costs and toll in terms of human suffering, and the undesirable side effect profile associated with statin therapy. Furthermore, while statins have been shown to reduce CV risk, patients on such therapies continue to have significant residual risk of a repeat event, such as a heart attack.
•Heart disease is the number one cause of death for both men and women in the United States, claiming approximately 1 million lives annually. (con'd below)
FOR IMMEDIATE RELEASE
Consumer Group Challenges FDA to Abide by Its Own Guidelines
Urges Reinstatement of SPA for Heart Drug Vascepa
The EPA Drug Initiative (EPADI) asserts that the FDA did not live up to its own scientific integrity standards in rescinding the Special Protocol Assessment (SPA) related to the “ANCHOR” sNDA for the triglyceride (TG) lowering drug, Vascepa, and urges that the Agency adhere to its own policies in the appeal of the SPA rescission decision.
Specifically, EPADI believes that in drawing conclusions from three other failed triglyceride-lowering studies (ACCORD-Lipid, AIM HIGH and HPS2 THRIVE) — each of which involved drugs, objectives/endpoints and patient characteristics different from those in the ANCHOR study — the Agency’s integrity has been compromised severely.
Consistent with the Agency’s own Staff Manual Guide issued on February 3, 2012 (SMG 9001.1), EPADI urges the FDA to strictly adhere to its own stated policy of placing scientific integrity at the forefront of its mission.
The first key principle of scientific integrity listed in this guide states “Maintaining a firm commitment to science-based, data-driven decision-making.” Maintaining scientific integrity is especially important given the very high legal threshold required to rescind a SPA. EPADI believes the Agency has not lived up to this policy commitment, in that:
•As most of the patients in ACCORD-Lipid, AIM HIGH and HPS2 THRIVE had normal or borderline elevated TG levels, these trials could not answer the question of whether TG lowering would be beneficial in patients with high TG levels. Thus, the Agency’s reviewing division erred in extrapolating that these three outcome trials proved that TG lowering therapy would not be beneficial in patients with high TG level (~ 200 and
BEDMINSTER, N.J., and DUBLIN, Ireland, Jan. 15, 2014 (GLOBE NEWSWIRE) -- Amarin Corporation plc (AMRN:$2.40,00$0.33,0015.94%) , a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health, announced today that the Division of Metabolism and Endocrinology Products (DMEP) within the U.S. Food and Drug Administration (FDA) notified the company today that a determination on Amarin's (AMRN:$2.40,00$0.33,0015.94%) request for reconsideration of DMEP's October 2013 decision to rescind the ANCHOR clinical trial Special Protocol Assessment (SPA) agreement will be delayed. FDA previously notified the company that it planned to convey its decision to Amarin no later than January 15, 2014. In today's communication, DMEP provided no definitive date for its planned response. Based on dialogue with DMEP, Amarin (AMRN:$2.40,00$0.33,0015.94%) does not expect the delay to be for a significant period of time.
Insiders filed Form 4s reflecting exercises of long-dated options and selling only so many of the new shares as were needed to pay for the exercises. Apparently holding the remaining shares. Bullish imo.
From Nature Genetics (note language "causally influence risk for CAD"):
Common variants associated with plasma triglycerides and risk for coronary artery disease
Ron Do, et al
Nature Genetics 45, 1345–1352 (2013) doi:10.1038/ng.2795
Received 20 February 2013 Accepted 13 September 2013 Published online 06 October 2013
Triglycerides are transported in plasma by specific triglyceride-rich
lipoproteins; in epidemiological studies, increased triglyceride levels
correlate with higher risk for coronary artery disease (CAD).
However, it is unclear whether this association reflects causal processes.
We used 185 common variants recently mapped for plasma lipids
I just submitted a comment to Dr. Ma's Citizen's Petition on the FDA website and in which I discussed the paper, quoted its results, and gave the citation. So, FDA now has it. May take several days for FDA to post the comment.
No approval is "automatic" with FDA, even where there is an (unrescinded or reinstated) SPA the terms of which have been met. To that extent, I disagree.
FDA is addressing Amariin's appeal from FDA's rescission of the SPA (separately from its disposition of the sNDA) likely because its lawyers advised them it would be prudent to do so. Possible reasons include: the SPA, and particularly the one stating grounds upon which one can be rescinded, are distinct from the regs relating to the sNDA; the SPA provides most of the framework by which the evidence offered in support of the sNDA must be evaluated; and the regulations' wording iimply that FDA, not AMRN, has the burden of showing grounds for the SPA's rescission, in contrast to AMRN's having the burden of proof/persuasion re it having met all requirements for approval of the sNDA.
AMRN's pressing their appeal from the SPA rescission was an important strategic move that ultimately was successful. FDA now has to sustain its burden of proof re the substantial scientific issue underlying the rationale for ANCHOR indication (that elevated trigs (200-499) is likely a reliable biomarker of CV disease such that lowering them to normal range likely lowers CV disease risk). If you have read the Citizen Petition or Dr. Ma's SA article you know that the 3 studies relied upon by Coleman et al at FDA are very weak support for FDA's position and, if anything, support (subgroup analysis) AMRN's position.
It's also a shot across the bow, with AMRN letting FDA know any further mistakes of a substantial nature may be subject to judicial review.
Still, FDA could do things less than approve ANCHOR because FDA has that much power. Thkey certainly should reinstate the SPA, but they could issue a CRL for some subjective reason and at least not be accused of having improperly rescinded the SPA. They shouldn't, but they could.
Let's hope they really want to get the science right and feel compelled to re-examine what happened.
FDA's saying that they now consider the appeal from FDA's rescission of ANCHOR SPA to be a matter separate (and separately addressable) from its disposition of the ANCHOR sNDA is a clear reversal of its earlier stated position that they are one issue. This reversal could be very significant.
FDA has the burden of showing the substantial scientific issue necessary under the regs in order to rescind the SPA. They will have a tough time doing so, at least if they have to use sound scientific method and data to do so.
AMRN has the burden to sustain its showing in support of the sNDA, which it obviously can do.
Hopefully someone over Coleman has taken a look at the basis for the criticism of the rescission and agrees it needs a careful review. We'll see.
Credit Ihub mb. I sent it on to the EPA Drug Initiative, the contact person for which emailed me this morning saying he had sent it on to their people. Hopefully, they will get it into the right hands promptly.
Eur J Prev Cardiol. 2013 Dec 16. [Epub ahead of print]
The association between dietary omega-3 fatty acids and cardiovascular death: the Singapore Chinese Health Study.
Koh AS, Pan A, Wang R, Odegaard AO, Pereira MA, Yuan JM, Koh WP.
Although studies suggest that omega-3 fatty acids intake may reduce cardiovascular disease (CVD) mortality risk, few studies have differentiated dietary eicosapentaenoic/docosahexaenoic acid (EPA/DHA) from alpha-linolenic acid (ALA), and epidemiological research in Asian populations is limited.
The Singapore Chinese Health Study is a population-based cohort that recruited 63,257 Chinese adults aged 45-74 years from 1993 to 1998. Usual diet was measured at recruitment using a validated semiquantitative food-frequency questionnaire, and mortality information was identified via registry linkage up to 31 December 2011. Cox proportional hazard models were used to calculate hazard ratios (HRs) with adjustment for potential confounders.
We documented 4780 cardiovascular deaths (including 2697 coronary heart disease (CHD) deaths and 1298 stroke deaths) during 890,473 person-years of follow up. Omega-3 fatty acids intake was monotonically associated with reduced risk of cardiovascular mortality. Compared to the lowest quartile, the HR was 0.88 (95% confidence interval, CI, 0.81-0.96), 0.88 (95% CI 0.80-0.97), and 0.83 (95% CI 0.74-0.92) for the second, third, and highest quartile, respectively (p-trend?=?0.003). Both EPA/DHA and ALA were independently associated with reduced risk of cardiovascular mortality: HR comparing extreme quartiles was 0.86 (95% CI 0.77-0.96, p-trend?=?0.002) and 0.81 (95% CI 0.73-0.90, p-trend?