Nevin Varghese

Nevin Varghese questioned the confidence in remlifanserin's 30mg and 60mg doses reproducing the exposure-response relationship seen with pimavanserin in ADP and Lewy body patients, and asked if the target efficacy gap versus pimavanserin's marketed dose could be quantified based on preclinical and Phase 1 PK data.

Answer

Elizabeth Thompson, EVP and Head of Research and Development, stated that confidence stems from pimavanserin's observed exposure-response, where neither ADP nor Lewy body appeared to be at maximum efficacy. She noted that even reproducing similar efficacy levels to pimavanserin's 34mg in a more robust, ADP-specific study would be meaningful, with additional efficacy being a 'cherry on top.' She acknowledged the need to test the differentiation between 30mg and 60mg doses.

Nevin Varghese asked about Acadia's confidence that remlifanserin's 30mg and 60mg doses will reproduce the exposure-response relationship seen with pimavanserin in ADP and Lewy Body patients, and if the target efficacy gap versus pimavanserin's marketed dose could be quantified.

Answer

Elizabeth Thompson, EVP and Head of Research and Development, stated confidence is based on pimavanserin's exposure-response not reaching maximum efficacy in prior studies. She noted that even reproducing similar efficacy levels in a more robust remlifanserin study would be meaningful, with additional efficacy being a bonus. Quantifying a precise efficacy gap is not possible at this stage.

Asked about the expected launch trajectory for CAPLYTA in MDD, its comparison to Vraylar's launch, and the potential competitive impact of KarXT in schizophrenia.

Answer

A rapid uptake in MDD is expected, similar to or better than analogs like Vraylar, due to CAPLYTA's strong clinical profile. They do not anticipate a significant impact from KarXT, as CAPLYTA's long-term growth is in mood disorders where KarXT doesn't compete, and CAPLYTA's tolerability profile is a key advantage in the schizophrenia switching market.