Antipsychotic from Lundbeck, Otsuka flops again in PhIII trials — this time in bipolar patients

New Lundbeck CEO Deborah Dunsire has more bad news to contend with, five months into her appointment. The Danish drugmaker — which is battling with generics eating into sales of three key drugs and a recent setback for schizophrenia — on Thursday said a pair of pivotal trials failed to show its blockbuster antipsychotic drug, brexpiprazole, helped patients with bipolar disorder.

Deborah Dunsire

The drug, discovered by Otsuka and partnered with the Japanese company, is already approved for use in major depression and schizophrenia and is sold under the brand name Rexulti.

The two, 3-week trials tested the drug versus a placebo in 650 bipolar I patients who experienced an acute manic episode that required hospitalization. The main goal of either trial was to show brexpiprazole induced a statistically significant improvement on a common rating scale used to assess mania symptoms based on a patient’s subjective reports and clinician observations.

Most trials testing drugs to treat psychiatric disorders fall prey to an inflated placebo effect. This case was no different — in both studies, a higher-than-expected placebo effect was detected, the companies said.

The duo — who did not break out the numbers reflecting the failure on Thursday — are conducting an analysis of the data, and will consequently determine the next steps for the program.

Leerink analysts said they were surprised by the failure, considering both Abilify and Allergan’s $AGN Vraylar — two other partial agonists on the D2/D3 receptors — have demonstrated efficacy in this indication, as well as various other antipsychotics currently being used to treat bipolar mania. “Amongst the possible psychiatry indications that could be pursued in this space, Bipolar I manic episodes is one of the more “low hanging fruit” indications, as it is often the initial bipolar spectrum approval that allows products to launch or expand in psychiatry – all of which adds to our surprise here…however, we will not make any changes to our sales estimates for Rexulti because we don’t include much sales for this indication anyway,” they wrote.

In 2017, two late-stage studies testing brexpiprazole for agitation triggered by Alzheimer’s dementia threw up mixed data, with one study successful and the other deemed a failure. Dunsire, who took the reins in September, was dealt a big setback in October with a Phase III failure of the company’s schizophrenia drug candidate, Lu AF35700. However, she had some cheer in November when brexpiprazole yielded success in a mid-stage study in patients with PTSD when given in combination with the antidepressant sertraline (Zoloft).

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