Amarin Corp Plc (AMRN)

[dogn]

Thoughts on future FDA approval of self-emulsifying ethyl-EPA (Mochida MND-2119)

With MND-2119, licensed by Amarin, apparently now approved in Japan, what is path to approval by FDA?

The paper "Bioequivalence [BE] Demonstration for O-3 Acid Ethyl Ester Formulations: Rationale for Modification of Current Guidance" suggests the FDA guidance "established for icosapent ethyl (EPA ethyl esters) [has] the primary measure of BE [as] baseline-adjusted total EPA in plasma lipids for both the fasting and fed states."

From the recent June 24, 2022 Journal of Clinical Lipidology paper "Efficacy and safety of self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (MND-2119) versus highly purified eicosapentaenoic acid ethyl ester in patients with hypertriglyceridemia: Results from a 12-week randomized, double-blind, active-controlled, phase 3 study":

Although the baseline plasma EPA concentrations of the subjects in this study (59.2 µg/mL and 61.2 µg/mL at MND-2119 2 g/day and 4 g/day, respectively; the following are in the same order) were lower than those in JELIS, the increase from the baseline values (122.2 µg/mL and 200.1 µg/mL, respectively) and post-dose plasma EPA concentrations (181.5 µg/mL and 261.2 µg/mL, respectively) were higher than those in JELIS.
...The baseline EPA concentration of the subjects in REDUCE-IT was 26.1 µg/mL and increased to 144.0 µg/mL after 1 year of continuous treatment, with a mean increase of 112.6 µg/mL. REDUCE-IT also showed that reduced risk of cardiovascular events was strongly associated with plasma EPA concentration12. In the current study, although the baseline values of plasma EPA concentrations were higher than ANCHOR and REDUCE-IT, post-dose EPA concentrations and increases from baseline were higher than that of ANCHOR in both MND-2119 doses, and higher than the results of REDUCE-IT at 1 year for MND-2119 at the 4 g/day dose.

What further data would the FDA need? Bioequivalence of MND-2119 demonstrated per established guidance.
dogn

ps I am curious if anyone knows where to locate the FDA established guidance. The BE paper above mentions a different "US Food and Drug Administration (FDA) draft guidance for establishing bioequivalence (BE) of ?-3 acid ethyl esters (containing both eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] as ethyl esters), used to treat severe hypertriglyceridemia" which I think I located at https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021654.pdf (last updated Aug. 2020). And does anyone know if/when this draft guidance became or may become final? Can't find anything more recent, and would like to see full final guidance for icosapent ethyl BE especially.