CHMP adopts negative opinion for iloperidone in schizophrenia and bipolar I disorder – Vanda Pharmaceuticals

The EMA has recommended the refusal of the marketing authorisation for Iloperidone Vanda Pharmaceuticals, a medicine intended for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The company that applied for authorisation, Vanda Pharmaceuticals Netherlands B.V., may ask for re-examination of the opinion within 15 days of receiving the opinion.

After assessing the data provided by the company, the Agency was of the opinion that the safety and efficacy of Iloperidone Vanda Pharmaceuticals had not been sufficiently demonstrated.

The Agency concluded that treatment with Iloperidone Vanda Pharmaceuticals is associated with pronounced QT prolongation (a change in the heart’s electrical activity which can cause a life-threatening heart rhythm abnormality) which is not outweighed by the benefits of treatment. The Agency considered that feasible and effective measures to manage and address this risk in clinical practice (including how to identify and monitor patients at higher risk of potentially fatal arrhythmias) had not been identified.

In patients with schizophrenia, this risk was not considered to be outweighed by the observed treatment effect, since the results of the short-term studies were not considered statistically robust after additional analyses. In addition, the Agency noted that the medicine starts to have an effect after 1.5 to 3 weeks of treatment, possibly because the dose of Iloperidone Vanda Pharmaceuticals has to be increased slowly, which is a concern as it is intended for immediate and continued treatment of schizophrenia.

In patients with acute manic or mixed episodes associated with bipolar I disorder, the risk of QT prolongation is also not considered to be outweighed by the observed effect in the short-term study, the lack of data comparing the medicine with other treatments or placebo beyond 4 weeks of treatment, as well as the delayed onset of effect.

Therefore, the Agency’s opinion was that the benefits of Iloperidone Vanda Pharmaceuticals did not outweigh its risks, and it recommended refusing marketing authorisation.