Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder: an appraisal of phase III clinical trials of schizophrenia-targeted therapies as found in US and EU clinical trial registries

ABSTRACT

Introduction: In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future.

Areas covered: Recent (post 2013) phase III clinical trials of schizophrenia-targeted therapies were found in US and EU clinical trial registries. Two hundred fifty-three trials were identified, that included 16 investigational compounds. The antipsychotics brexpiprazole and cariprazine have been approved in the US, and although both are dopamine D2 receptor partial agonists, they differ markedly in their pharmacodynamic profiles. Encenicline and valbenazine are first-in-class candidates for treatment of cognitive impairment associated with schizophrenia (CIAS) and tardive dyskinesia, respectively. Eleven add-on compounds were previously approved for other therapeutic indications and are for the most part being studied at academic medical centers and smaller pharmaceutical companies for negative symptoms and CIAS or for specific populations (comorbidities, antipsychotic-induced obesity).

Expert opinion: Promising new agents are emerging for schizophrenia and schizoaffective disorder. In addition to better-tolerated antipsychotics that treat positive symptoms, we could see the arrival of the first effective drug for negative symptoms and CIAS, which would strongly facilitate the ultimate goal of recovery in persons with schizophrenia.

KEYWORDS:

• Schizophrenia
• phase III
• clinical trials
• brexpiprazole
• encenicline
• valbenazine
• cariprazine

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Acknowledgements

We are grateful to Kenji Maeda (Otsuka Pharmaceutical, Tokushima, Japan) for providing information about brexpiprazole.

Declaration of interest

The authors have received no payment for the preparation of this manuscript. R P Garay and A Hameg are members of a non-profit association for therapeutic innovation (Craven, Villemoisson-sur-Orge, France). In the past 36 months L Citrome has engaged in collaborative research with, or received consulting or speaking fees, from: Alexza, Alkermes, Allergan, AstraZeneca, Avanir, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Forum, Genentech, Janssen, Jazz, Lundbeck, Merck, Medivation, Mylan, Novartis, Noven, Otsuka, Pfizer, Reckitt Benckiser, Reviva, Shire, Sunovion, Takeda, Teva, Valeant and Vanda. L Samalin has received honoraria for conferences and consulting from AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Lundbeck A/S, Otsuka and Takeda. CC Liu has received honoraria for conferences and consulting from AstraZeneca, Janssen-Cilag, and Otsuka. M S Thomsen declares support for consultancy from Bionomics. C U Correll has been a consultant and/ or advisor to or has received honoraria from AbbVie, Acadia, Actavis, Alkermes, Eli Lilly, Forum, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Janssen/Johnson & Johnson; Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Reviva, Roche, Sunovion, Supernus, Takeda and Teva. He has received grant support from Bristol-Meyers Squibb, Otsuka, Lundbeck and Takeda. P M Llorca declares grant support in addition to support for consultancy, expertise and honoraria for conferences from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., Janssen-Cilag, Lundbeck A/S, Otsuka, Roche, and Sanofi Aventis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.