I must admit it, I am surprised by the scale of the risk reduction that Amarin Corporation’s Vascepa (icosapent ethyl) has delivered in the REDUCE-IT cardiovascular outcomes trial (CVOT).
REDUCEd-IT and more
In this trial of more than 8,000 statin-treated primary and secondary CV prevention patients with moderately raised triglyceride (TGs) levels, Vascepa was associated with a staggering 25% reduction in the risk of major adverse CV events. Elevated TGs are accepted as providing additional CV risk, but it is low density lipoprotein (LDL)-cholesterol with the strongest link to atherosclerosis and CV disease.
Earlier CVOTs for omega-3 fatty acid compounds, including the GISSI-Prevenzione and JELIS trials, have also demonstrated CV benefits. However, based on multiple positive CVOTs, the statins became the dominant lipid modifying therapy. The consensus among thought leaders was that the body of evidence for additional CV benefit from omega-3 fatty acids was inconclusive. LDL-cholesterol remained the key lipid target, but new drugs targeting LDL-cholesterol have failed to provide the risk reduction observed with Vascepa; the powerful PCSK9 inhibitors only achieved a 15% CV risk reduction.
So, how has Vascepa emerged as a game changer for CV disease prevention? Three factors immediately come to mind:
- Trial design
- Optimal treatment
The right stuff? The right trial? The right dose?
Vascepa is an ethyl ester of eicosapentenoic acid (EPA). Most other prescription omega-3 fatty acid compounds contain a combination of EPA and docosahexaenoic acid (DHA). GSK’s Lovaza, which combines EPA and DHA, increases LDL-cholesterol levels; Vascepa does not.
REDUCE-IT was also a well-designed trial. The mean follow-up period for this study was almost 5 years and a large difference in outcomes was observed. In contrast, the mean duration of the CVOTs for the PCSK9 inhibitors was less than 3 years, and we were left with a moderate CV benefit plus the hint of better outcomes in the future.
Moreover, REDUCE-IT assessed the maximal prescription dose of Vascepa. Previous trials have often evaluated suboptimal dosing regimens for omega-3-based drugs.
Of course, tantalizing question remain. Does Vascepa reduce all-cause or CV mortality rates? Will the CV benefits be seen in both the primary and secondary prevention groups? The presentation of the trial at the American Heart Association Scientific Sessions in November will provide these and other details and I am sure will stimulate more research and development targeting TGs and residual CV risk. And will the FDA now consider approving more drugs to treat patients with moderately raised TG level?
On the back of the REDUCE-IT results we expect approvals in numerous new regions expanding Vascepa’s availability beyond the United States. However, pricing will need to remain competitive for Vascepa’s uptake to really accelerate. Having said that, you might not blame Amarin for placing a premium on what seems to be a practice-changing therapeutic.
For further information see DRG’s Dyslipidemia Market Assessment Suite, click here. Please note, DRG’s 2017-2027 market forecast for dyslipidemia is due to publish in November 2018.