FDA approves CV label expansion for Amarin’s Vascepa – December 16, 2019

Executive Highlights

  • Amarin Friday announced FDA approval of its CV label expansion for Vascepa (icosapent ethyl) in adults with elevated triglycerides ≥150 mg/dL and either (i) established CVD; or type 2 diabetes and two or more additional risk factors for CVD. Further details were shared during a highly informative webcast yesterday led by Amarin CEO Mr. John Thero.

  • Of note, the FDA indication is for a population broader than just that studied in REDUCE-IT, and Amarin CMO Dr. Craig Granowitz estimated a potential population of 6 million patients in the United States.

  • Financially, Amarin increased its 2019 year-end guidance for total net revenue from $410 to $425 million following the approval.

As expected, Amarin announced FDA approval of its CV label expansion for Vascepa (icosapent ethyl), in addition to the drug’s prior indication for adults with severe hypertriglyceridemia (≥500 mg/dL). The new label specifies Vascepa as an adjunct to “maximally tolerated statin therapies” to reduce the risk of MI, stroke, coronary revascularization and unstable angina requiring hospitalization for adults with elevated triglyceride levels of ≥150 mg/dL and either (i) established CVD; or (ii) diabetes and two or more additional risk factors for CV disease.

Consequently, Vascepa can now be used for both those with established CVD (secondary prevention) and those with diabetes and risk factors (primary prevention). Of note, CV death – a component of the composite 5P-MACE primary outcome from the REDUCE-IT CVOT – was not included in the expanded indication, though it was listed as part of the full REDUCE-IT results on the label. As a reminder, Vascepa demonstrated a 25% relative risk reduction with Vascepa vs. placebo on the primary endpoint of CV death, MI, coronary revascularization, or unstable angina during the trial.


Clinical Implications of Label Wording

CEO of Amarin Mr. John Thero communicated the clinical practicality of the new label’s phrasing during the company’s webcast this morning, noting the high level of ‘prescriber leeway’ allowed by the label. He stated, “In completing this label, we saw wording that could be clearly and efficiently used in medical practice. As such, the label uses shorthand terminology such as established cardiovascular disease and general references such as two or more risk factors for cardiovascular disease. This deliberate phrasing enables broad use in physician discretion.” In particular, management hinted at less stringent interpretation of three key indication points: (i) risk factors of CVD; (ii) minimum triglyceride levels; and (iii) statin usage.

  • The FDA’s language does not specify risk factors needed for patients to be prescribed the medication, though Amarin leadership listed (i) at least 50 years of age; (ii) current or recent smoking; (iii) hypertension; (iv) low HDL; (v) high hsCRP; (vi) BMI >25; (vii) renal dysfunction; (viii) retinopathy with micro or macroalbuminuria; and (ix) ankle brachial index (ADI) <0.9 without intermittent claudication as likely examples. In the REDUCE-IT trial, however, selected additional baseline risk factors included hypertension, type 2 diabetes, eGFR <60 mL/min/1.73 m2, congestive heart failure, and and current daily cigarette smoking.  Of note, participants in the REDUCE-IT trial were defined as having diabetes with an age limitation and at least one other CV risk factor, making the FDA’s lack of an age or LDL-C range limitation even broader than trial inclusion criteria.

  • While the new label specifies minimum triglycerides of 150 mg/dL, Mr. Thero did choose to highlight that “multiple national and international guidelines and physician statements now guide prescribes to prescribe Vascepa starting at a lower 135 mg/dL threshold,” including the National Lipid Association, European Society of Cardiology, European Atherosclerosis Society, American Heart Association, and American Diabetes Association. Traditionally, 135 to 150 mg/dL has been considered within the normal range of triglycerides, but a growing body of evidence suggests that even levels below 100 mg/dL are linked to increased risk of CVD. Importantly, while REDUCE-IT was designed to study patients with triglycerides ≥150 mg/dL, study inclusion only required triglycerides ≥135 mg/dL to allow for 10% variability, further backing lower triglyceride usage. Mr. Thero summed this point up by stating, “in practice, we believe many prescribers will be guided by guidelines in their view of the risk benefit profile of VASCEPA to treat patients in the 135-150 mg/dL range, even if below the 150 milligrams threshold in an FDA approved labeling.”

  • Label phrasing of “patients on maximally tolerated statin therapies” deliberately allows greater flexibility to prescribers for “patients who are unable or unwilling to take intensive statin therapy.” According to a 2018 article published in the American Journal of Cardiovascular Drugs, a substantial 20% of individuals clinically indicated to receive statin therapy are unable to take a daily statin due to intolerance.

Patient Population

According to Amarin’s Chief Medical Officer Dr. Craig Granowitz, approximately 12 million of the 38 million statin-taking patients in the US have triglyceride levels of ≥150 mg/dL, and more than half of those patients are also estimated to have established CVD or diabetes and multiple other CVD risk factors. We take this direct patient population of ~six million to be a conservative estimate, considering that >50 million American adults have triglyceride levels of ≥150 mg/dL. These numbers reflect a substantial uptick from the two to three million US adults with triglycerides ≥500 mg/dL previously indicated for Vascepa usage.

Financials and Commercial Rollout

Financially, Amarin increased its year-end guidance for total net revenue from $410 to $425 million following the approval. Similarly, predicted net revenue for 2020 increased from $650 million to $700 million, primarily driven by sales of Vascepa in the US.

  • Further promotion of Vascepa seems to be in full swing, as the company is on track to double its sales force to a total of 800 representatives. Promotion of Vascepa’s new indication to healthcare professionals will begin “as soon as [Amarin’s] salesforce is trained,” and direct-to-consumer advertising is scheduled for approval and initiation by mid-2020. During the webcast, CMO Dr. Granowitz noted that medical education forums and publications designed to expand awareness about Vascepa have also been planned. For specific education, Dr. Granowitz cited (i) the need to abandon earlier generation, low triglyceride products that have failed to demonstrated CV risk reduction such as fibrates, niacin, and omega-3 mixers; and (ii) the fact that Vascepa is not a standard fish oil.

Vascepa in the News

The regulatory decision follows a unanimous vote for Vascepa’s CV indication at a mid-November FDA Ad Comm meeting. While all sixteen panelists agreed that results from REDUCE-IT support an indication, only ten expressed support for use of Vascepa in both primary and secondary prevention populations, while five voted for sole use in secondary prevention, and one member remained undecided.

  • An ICER analysis of the drug presented at AHA 2019 demonstrated cost-effectiveness at its price point of $4.16/day for over 85% of the model’s simulations. Results from REDUCE-IT were used to determine lifetime health benefits, health care costs, and cost-effectiveness of Vascepa vs. placebo, which came out to 11.61 and 11.35 QALYs over patients’ lifetimes for Vascepa and placebo, respectively.

Updated FDA Label for Vascepa


--by Rhea Teng, Martin Kurian, and Kelly Close