Acadia Moving Ahead With 5HT2A Agonist In Parkinson’s Psychosis, Schizophrenia

The company is seeking to partner ACP-103 for schizophrenia following positive Phase II data.

Acadia Pharmaceuticals' commercial strategy for the investigational 5HT2A inverse agonist ACP-103 will include partnering to address large primary care-targeted indications like schizophrenia and insomnia, as well as the development of a sales force for specialty indications like Parkinson's disease psychosis.

Chief Executive Officer Uli Hacksell updated investors on the company's commercial strategy at the Lehman Brothers Global Healthcare Conference March 20 after releasing positive Phase II data on ACP-103 a day earlier.

"When it comes to our commercial strategy, it's based really on the ability of Acadia to market things effectively," Hacksell said.

For example, with ACP-103 in a specialist indication like Parkinson's disease psychosis, it would be possible to market the drug in the U.S. with a small dedicated sales force, so Acadia could market the drug on its own, he explained.

"Schizophrenia and sleep maintenance insomnia are completely different kinds of indications. Here, you need a large sales force and a very dedicated and strong marketing effort to be successful," Hacksell said. "Here we want to complete the Phase II clinical programs so that we have demonstrated efficacy and safety of our drugs and then start to explore potential strategic alliances that can help us first, to complete a successful Phase III program and second, to optimize the value of our products on the market."

For schizophrenia, a potential alliance could come in the near-term after Acadia released top-line results of a Phase II trial that met its primary endpoint. The study showed treatment with ACP-103 resulted in statistically significant antipsychotic efficacy and an improved side effect profile when used as a concomitant therapy with Johnson & Johnson's Risperdal (risperidone) or generic haloperidol.

The results could indicate an emerging new treatment paradigm for schizophrenia, the exec said.

The six-week randomized, double-blind, placebo-controlled trial enrolled 423 patients in the U.S. and Brazil. Patients were assigned to one of five study arms: ACP-103 plus low-dose risperidone; low-dose risperidone plus placebo; high-dose risperidone plus placebo; ACP-103 plus haloperidol; or haloperidol plus placebo.

The primary endpoint of the study was antipsychotic efficacy after 42 days as measured by a reduction in the Positive and Negative Syndrome Scale.

ACP-103 combined with the low-dose of risperidone (2 mg) showed a 23 point (27.4 percent) improvement in the PANSS score after 42 days, compared to a 16.6 point (19 percent) improvement in the low-dose risperidone arm plus placebo. The efficacy was similar to high-dose risperidone (6 mg) plus placebo, which resulted in a 23.2 point (26.4 percent) improvement.

Co-therapy with ACP-103 also provided a significantly faster onset of action, with 50 percent more patients in the ACP-103/risperidone arm responding to treatment after two weeks, compared to either the risperidone LD or risperidone HD arms.

Patients in the co-therapy arm also had 50 percent less weight gain than patients in the risperidone arm, which trends to statistical significance, according to the company.

The firm is also moving ahead with a Phase III trial evaluating ACP-103 in Parkinson's disease psychosis, a disorder for which there is currently no approved treatment. The company plans to begin the first of two Phase III studies in the first half of the year, evaluating the compound on top of levodopa therapy.

"We expect to be able to completely differentiate ACP-103 from existing off-label antipsychotic drugs," Hacksell said. "We hope to be able to develop the first drug approved in the U.S. for this indication."

Acadia is also evaluating ACP-103 for sleep maintenance insomnia, and has completed a proof of concept study showing an increase in deep sleep among patients treated with ACP-103 once a day for two weeks.

-Jessica Merrill ([email protected])