Pimavanserin and Persistence

Acadia Pharmaceuticals is one of the very few survivors from the generation of neuropharm companies born in the early-mid 1990s. As is the case for many small firms, their prospects, were eventually and essentially condensed into one project, pimavanserin, a 5HT-2a inverse agonist with antipsychotic effects. Because it does not have direct dopamine-antagonist effects, it was envisioned as a treatment for Parkinsonian psychosis, where motor functioning is further impaired by DA-blockers. Acadia’s other research, indeed their very existence, became contingent upon pimavanserin. External factors played a role in this as well: Biovail, during its all-too-brief renaissance of neuro inlicensing, partnered pimavanserin when it was in its first Phase III testing for Parkinsonian psychosis, and sustained that partnership even after the first Phase III trial failed. Unfortunately, Valeant’s acquisition of Biovail put an end to that partnership and the label-expansion agenda behind it.
Acadia’s revamped, single-dose (40mg) Phase III program has now reported its first data, and pimavanserin provided a robust effect on Parkinsonian psychosis, enhanced performance on secondary endpoints, and did not cause any worsening of motor symptoms. Acadia could not have asked for better results from this Phase III trial, in what was essentially a do-or-die moment for the company. Another Phase III must be carried out, but we are very optimistic that the design and enrollment criteria that worked well for this trial will work again. Acadia will need a partner to fully maximize pimavanserin’s potential, which is could first expand into psychosis associated with Alzheimer’s, but might be fruitfully considered as a dose-sparing adjunct in the treatment of schizophrenia, reducing the dose-related side effects associated with all current antipsychotic drugs, albeit in different profiles and proportions.
There are a few lessons here, most of which relate to what we will call adaptive persistence. Acadia has been steadfastly focused on pimavanserin for the past four or more years. Give the late and lamented Biovail credit as well: They could have simply walked away from pimavanserin and Acadia after the first Phase III failed, and might have been applauded by those who believe pharma doesn’t kill its floundering projects fast enough. But they saw that the issue was dosing, revamped the partnership, and when Valeant then did walk away, they had to provide some funding to Acadia, money that was crucial to the program and Acadia’s survival. This does not by any means prove that all trial failures require or deserve resurrection, but there is a place for adaptive, rational persistence. Now, Acadia has an eminently partnerable success on its hands.

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One Response to Pimavanserin and Persistence

  1. Raymond T. Bartus says:

    Nice ‘perspective’ on this ‘good news’ story, Harry!

    Best wishes,

    Ray

    Raymond T. Bartus, Ph.D.

    Exec Vice President and

    Chief Scientific Officer
    Ceregene, Inc.

    858-458-8834

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