Forest Laboratories Inc. (FRX) and Gedeon Richter Plc. announced that the U.S. Federal Drug Administration (FDA) issued a complete response letter regarding the New Drug Application (NDA) for cariprazine, an atypical antipsychotic for the treatment of schizophrenia and for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
In 2008, the FDA began issuing complete response letters to companies to communicate that an application for a new drug (NDA) cannot be approved as filed. Previously, the FDA issued approvable or not approvable letters, leaving drug developers in the dark as to why a particular application was rejected. The FDA may issue a complete response letter for a number of reasons, from inadequate safety and efficacy data and how testing was performed to factors dealing with how the product will be manufactured. Complete response letters may or may not be made public. A complete response letter will describe all of the specific deficiencies that the agency has identified in an application or abbreviated application.
Atypical antipsychotics, such as Bristol Myers’ (BMY) Abilify, Eli Lilly’s (LLY) Zyprexa, and generic forms of Risperidone and Quetiapine, are widely used to treat schizophrenia, bipolar disorder, and occasionally in complex depression. While the drugs have a number of safety and efficacy benefits relative to first generation antipsychotics, in the past decade there have been growing concerns about potential serious metabolic side effects such as significant weight gain leading to increased diabetes and cardiovascular risks. As atypicals are being more widely marketed and prescribed as adjunct therapy to patients with moderate depression, the FDA is focused on understanding whether new atypicals will carry the same side effects/risks.
According to FRX, the FDA letter acknowledged that the application showed the efficacy of cariprazine in treating schizophrenia and mania associated with bipolar disorder; however the FDA indicated the need for more clinical data. FRX commented that “Given the complex pharmacokinetics and metabolism of cariprazine, we believe this request was made to better define the optimal dosing regimen to maintain the demonstrated efficacy, while minimizing the potential for the development of adverse events generally associated with this class of drug.”
In 2012, the FDA approved Dainippon Sumitomo Pharma’s atypical antipsychotic, Latuda. Latuda’s NDA included specific investigations into both weight gain and increases in cholesterol.
Forest and Gedeon Richter plan to meet with the FDA in the very near future to discuss the complete response letter. It is not yet clear whether the companies will need to conduct specific studies related to metabolic issues or whether it is existing data that can be harvested and added to the NDA.