The development of new therapeutics for the treatment of psychiatric diseases has been challenging for drugmakers in recent years. Roche's (OTC:RHHBY) potential schizophrenia agent bitopertin adds another failure to the mix as two of six Phase III studies show that the treatment failed to beat placebo.
Many pharmaceutical companies have shifted away from the neuroscience space and into other therapeutic areas, such as diabetes. The little development for psychiatric medications that is happening mostly centralizes around new indications for existing drugs or new agents that work under functionally the same mechanism as prior generations, but perhaps with minimally improved side effect profiles or efficacy .
Bitopertin, however, could have been a breakthrough for schizophrenia. The medication was being evaluated for use against the "negative" symptoms of schizophrenia which are notoriously hard to treat, and bitopertin would have been the first schizophrenia drug specifically targeted for negative symptoms. These negative symptoms include anhedonia (lack of interest), flattened affect, social withdrawal, and similar effects... in short, almost the opposite of the "classic" and "positive" symptoms of schizophrenia depicted in media such as hallucinations, delusions, and paranoia.
Phase II results in 2009 showed promise for bitopertin's efficacy in negative symptoms and spurred most of the optimism for the drug's projected sale potential. The two failed Phase III trials looked at adults with persistent schizophrenia of predominantly negative symptoms with their symptoms scored on the positive and negative symptom scale (PANSS ). After 24 weeks, patients showed a lack of response to bitopertin combined with antipsychotic therapy as compared to placebo. Its safety and patient tolerance was similar to the prior Phase II trial.
Of the remaining Phase III trials left, one looks at negative symptoms and the remaining three look at poorly controlled positive symptoms such as hallucinations and delusions.
Biopertin was projected to around $2 billion in peak sales with drug approval targeted for 2015. Roche states that it is not yet abandoning the product, but with only one trial left looking at negative symptoms it seems that the blockbuster potential of bitopertin is already on the wayside.
Even if the remaining trials show that it addresses positive symptoms such as hallucinations and delusions, it will just be another drug to an already saturated field of antipsychotics. These symptoms are already treated with medications like AstraZeneca's (NYSE: AZN) Seroquel, Otsuka's Abilify, Johnson & Johnson's (NYSE: JNJ) Risperdal, Eli Lilly's (NYSE: LLY) Zyprexa, and Pfizer's (NYSE: PFE) Geodon. This will be difficult to compete with given that most of those drugs have already undergone patent expiry, with the exception of AstraZeneca's Seroquel XR (set for expiration 2017), and Otsuka's Abilify (set for expiration October 2014.)
While the news of bitopertin's failure is certainly a blow for Roche, the company is diversified enough to be able to absorb the impact. Strong in cancer, Roche has a very strong portfolio of biologics internally and is aggressively looking at partnerships and acquisitions. In its own pipeline, it has several agents for Alzheimer's disease, multiple sclerosis and of course cancer; via external partnerships, it has made way into Parkinson's disease (with Santaris' Prothena), antibiotics (with Polyphor), and of course cancer . With this portfolio and successful restructuring efforts, it's doubtful that bitopertin will be commercialized, but Roche's robust pipeline indicates that the company is still on stable footing over the long-term.