Forest attempts to squeeze cariprazine into the crowded antipsychotic market.
By Daniel Chancellor, Lead Analyst
7 December 2012
I am a Lead Analyst covering the CNS and rare disease markets at Datamonitor Healthcare. I joined in early 2010, having ...
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Cariprazine is set to become the latest drug to enter the crowded antipsychotic market following its NDA submission for schizophrenia and bipolar mania. Despite consistent efficacy, the drug’s side-effect profile will be limiting, especially in a market now dominated by generics. Nevertheless, opportunities for differentiation remain, with Forest already looking toward additional approvals.
The New Drug Application (NDA) for cariprazine (Forest/Gedeon Richter) is based on positive data accumulated from six placebo-controlled studies in both schizophrenia and bipolar mania, which together enrolled over 2,700 patients. The drug was associated with an approximate 6-10 point treatment effect on the Positive and Negative Syndrome Scale (PANSS) and a 4-6 point effect on the Young Mania Rating Scale (YRMS). Such a consistent efficacy signal in late-stage development – all pivotal, registration trials were positive – is a rare occurrence in psychiatry and cariprazine’s antipsychotic activity has been proven beyond doubt. Cariprazine is a D2 and D3 receptor partial agonist and belongs to the well-established atypical antipsychotic class, although uniquely has preferential binding at the D3 receptor.
In its press release, Forest stated that pooled data across its Phase III program found that the most commonly reported adverse events (incidence of 5% or more and double placebo) were akathisia, extrapyramidal symptoms (EPS), dyspepsia, restlessness, tremor, fatigue, and vomiting. Furthermore, in a long-term extension of a schizophrenia trial presented at the 2012 American Psychiatric Association Annual Meeting, no fewer than 17 different adverse events had an incidence of at least 5%.
The consistent efficacy of cariprazine comes with a significant tolerability trade-off. While the adverse events reported are all typical of the class as a whole, cariprazine appears to be associated with the negative features of several antipsychotics, such as EPS (risperidone), somnolence (quetiapine), and possibly metabolic effects (olanzapine). As prescribing decisions in schizophrenia and bipolar disorder can often be driven by a drug’s side-effect profile, such a range of possible adverse events could make cariprazine an unattractive treatment option.
Over the past decade, the atypical antipsychotic class has produced numerous blockbuster brands, although this golden era is coming to an end as generic formulations flood the market. Recent new antipsychotic launches, such as Saphris (asenapine; Merck & Co.), Fanapt (iloperidone; Novartis), and Latuda (lurasidone; Dainippon Sumitomo), have all struggled to emulate the success of their predecessors. In light of its lack of differentiation from the class, Datamonitor believes that cariprazine will face similar struggles and sales growth will be slow.
One possible avenue for further exploration, which may provide Forest with a competitive advantage, is to explore any possible pro-cognitive effect of cariprazine treatment. Schizophrenia and bipolar disorder can often be characterized by cognitive deficits, and there is mounting evidence for the involvement of the D3 receptor in cognitive processes. If successful, cariprazine is likely to face competition from Latuda, which has also revealed glimpses of efficacy in such patients. However, Forest’s immediate development plans for cariprazine are in the treatment of bipolar depression and major depressive disorder, as well as in relapse prevention in schizophrenia.