Antipsychotics: What Comes Next?

In my post of March 6, 2013, I discussed the approval of the first inhaled antipsychotic (Adasuve – Staccato loxapine), which is expected to be available in a few months. In the next few years, new antipsychotics and new pharmaceutical formulations of already approved substances can be expected to reach the market that will enrich the available armamentarium . These compounds I want to briefly introduce here.I confine myself here to the drugs that are at least in Phase III clinical trials. Detailed characterizations will follow as these substances are introduced to the market.

Aripiprazole Lauroxil (ALKS-9070): This is a prodrug, which is metabolized after injection to the well-known aripiprazole. It is a depot preparation for a four weekly injection. Developer is the American company Alkermes, which specializes on providing substances available in depot formulations.

Aripiprazole Depot: This preparation is already approved in the U.S. as Abilify Maintena, the application for approval in Europe is filed. Developers are the Japanese company Otsuka, who has already developed the oral form of aripiprazole, and the Danish company Lundbeck. I will shortly publish a detailed post on this compound.

Bitopertin (RG-1678): The inhibitor of the glycine transporter type 1 (GlyT1), which is being developed by Roche, is currently one of the most interesting new developments. The drug is given as an add-on to therapy with one of the conventional antidopaminergic antipsychotics. The goal is the improvement of negative symptoms, and possibly also of persistent positive symptoms.

BL-1020 (CYP-1020): Here, the first-generation antipsychotic perphenazine is esterified with GABA. The ester is cleaved in the brain and GABA is released there, which is supposed to lead to pro-cognitive effects. In a first study, there was an effect on cognitive deficits that went beyond that of placebo and risperidone. The manufacturer of the drug, the Israeli company BioLineRx, however, announced in a press release on March 20, 2013,  that it had stopped a further study (CLARITY trial) after an interim analysis, since the achievement of the primary endpoint (superiority over risperidone in terms of cognitive deficits) would no longer be expected. The future of the substance is now unclear.

Brexpiprazole (OPC-34712): This substance is also jointly developed by Otsuka and Lundbeck. It comes from the series of the partial dopamine agonist from the laboratories of Otsuka and is supposed to represent a development of aripiprazole. It is currently tested in the indications of depression (as an add-on), schizophrenia and attention deficit hyperactivity disorder (ADHD) .

Cariprazine (RGH-188): Cariprazine is a partial agonist at dopamine D2 and D3 receptors with the particularity that the affinity to D3 is significantly higher than for D2 receptors. Whether the substance behaves differently clinically than, for example, aripiprazole, will have to be demonstrated in further studies and clinical practice. Cariprazine is jointly developed by the Hungarian company Gedeon Richter and the American Forest Laboratories.

Paliperidone palmitate 3 Month (PP3M): This preparation is being developed by Johnson & Johnson/Janssen Cilag together with the American Alkermes. The established depot preparation paliperidone palmitate, which is usually administered in four weekly intervals, is here injected in higher doses and other pharmaceutical preparation every three months.

Pimavanserin (ACP-103): Pimavanserin is a very selective inverse agonist at serotonin 5HT2A receptor. The drug is being developed by Acadia Pharmaceuticals. It has been tested for the treatment of psychosis in Parkinson’s disease and as an add-on to antipsychotic treatment in schizophrenia. In both indications studies were published that show mixed results.

Zicronapine (Lu 31-130): The substance is being developed by Lundbeck. It antagonizes D1, D2 and 5-HT2A receptors. Thus, pharmacologically it is very close to the available second-generation antipsychotics. Published data on the pharmacology of the substance are lacking. The available clinical studies have demonstrated the efficacy of the substance, but it in a market that will soon be occupied by a number of generic drugs it can only prevail if it has advantages over its competitors.

It will be interesting to see which of these substances, if they are being approved, reach the German market, since this is only attractive to the pharmaceutical industry when the German IQWiG comes to the conclusion that the new substance brings added benefits.


This post is also available in: German

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