Citi note. FYI
We previously highlighted that the success of canakinumab in the ph3 CANTOS outcomes trial suggests that reducing inflammation can reduce CV events. Since Vascepa also has anti-inflammatory effects, we see this as an encouraging sign for AMRN's ongoing REDUCE-IT outcomes trial. If Vascepa's anti-inflammatory effects contributed to the positive results seen in the JELIS outcomes trial, then there's a few reasons we would expect a greater benefit from inflammation in REDUCE-IT. Recall that JELIS was an open-label outcomes trial conducted in Japan that showed a 19% Relative Risk Reduction for Vascepa compared to placebo. 1. Vascepa dosing is higher in REDUCE-IT than in JELIS – In REDUCE-IT, 4g of Vascepa is given daily, compared to 1.8g in JELIS. We expect this higher dose to contribute to a greater anti-inflammatory effect in REDUCE-IT than JELIS. This is because in both the ANCHOR and MARINE studies of Vascepa the 4g dose arm had more than a 3x lowering in the inflammatory patient population to REDUCE-IT], and -36% for 4g vs. -10% for 2g in MARINE). 2. Statin dosing is higher in REDUCE-IT than in JELIS – In both REDUCE-IT and JELIS, all patients in both arms are treated with statins. However, in JELIS patients received just 10mg of pravastatin or 5mg of simvastatin compared to the more typical dose ranges in the US of 10-80mg and 10-40mg respectively. This is an important difference that could lead to a greater decrease in inflammation in REDUCE-IT than JELIS, because in ANCHOR patients on 2g Vascepa and low dose statins (resembling JELIS) had a 10% increase in CRP (not statistically significant), compared to the 4g Vascepa and medium/high dose statin groups (resembling REDUCE-IT) which had a 23-29% decrease in CRP (p < 0.05). 3. Fish intake is likely lower in REDUCE-IT than in JELIS – We expect the worldwide REDUCE-IT trial will have lower dietary fish intake compared to JELIS which was solely conducted in Japan, a country that reportedly has above average fish consumption. Since the active ingredient of Vascepa is EPA, which is found in fish, this could lead to a greater benefit on CRP and other measures in REDUCE-IT than JELIS, in which participants likely had higher baseline levels of EPA. Finally, some remarks on readthrough from the REVEAL outcomes trial of the CETP inhibitor anacetrapib to several stocks in our coverage. We see the positive results announced last week as providing another example that supports drugs can show an outcomes benefit on top of statins, which is encouraging for REDUCE-IT, and FGEN's outcomes trials of Roxadustat.
