Prospects for Roche’s candidate schizophrenia treatment bitopertin are looking shaky after the drug failed the first two of six planned phase III trials.
Bitopertin is the first in a new class of medicines known as glycine reuptake inhibitors and is being developed primarily to treat the negative symptoms of schizophrenia, such as social withdrawal and lack of motivation.
While so-called positive symptoms of schizophrenia such as hallucinations and delusions are fairly well-managed with existing anti-psychotic medicines, negative symptoms have proved a tougher challenge.
Approximately two-thirds of schizophrenia patients experience significant negative symptoms, and it has been suggested that a drug able to control them could become a blockbuster product. Roche has also highlighted the drug as an important pipeline product.
The first two phase III studies to report focused on bitopertin’s ability to treat adults with persistent, predominant negative symptoms of schizophrenia, but unfortunately giving bitopertin as an add-on to background antipsychotic therapy failed to meet the primary endpoint of a significant improvement on the positive and negative symptom scale (PANSS), said Roche.
A third phase III trial in patients with persistent negative symptoms is ongoing, with three more looking at the drug’s role in patients who continue to have positive symptoms despite antipsychotic therapy.
Roche’s chief medical officer Sandra Horning said the company would wait for the results of the remaining studies before taking a decision on the future of bitopertin, but acknowledged that the data is hugely disappointing for schizophrenia patients grappling with these debilitating symptoms.
The schizophrenia market has been shrinking in recent years as massively successful antipsychotic medicines such as Lilly’s Zyprexa (olanzapine), AstraZeneca/Astellas’ Seroquel (quetiapine) and Bristol-Myers Squibb/Otsuka Pharmaceutical’s Abilify (aripiprazole) lost patent protection and succumbed to generic competition.
Meanwhile, pharma companies have struggled to bring novel antipsychotics to market, with Lilly dropping pomaglumetad methionil in 2012 and Targacept giving up on TC-5619 towards the end of last year. Like bitopertin both of these were being tested as add-on drugs to tackle negative symptoms, but had different mechanisms of action.
Analysts have suggested in the past that bitopertin could achieve sales of $3bn or more if it proves effective in managing withdrawal and lack of motivation in schizophrenia.