Roche cancels two phase III Alzheimer’s trials

Roche and AC Immune have discontinued phase III trials of their Alzheimer’s disease drug crenezumab after an interim analysis indicated it would not hit its primary endpoint.

Crenezumab is an anti-beta-amyloid molecule that was being investigated in people with prodromal to mild sporadic Alzheimer’s disease (AD) in the CREAD 1 and CREAD 2 phase III trials.

An Independent Data Monitoring Committee analysis indicated that the drug was unlikely to meet its primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score.

This is just the latest in a huge number of failures in the Alzheimer’s space over the past year, with companies including Lundbeck, Boehringer Ingelheim, Pfizer and Eli Lilly all seeing disappointing results or scrapping their programmes altogether.

Like crenezumab, many of these drugs were focussing on the hypothesis that AD is caused by amyloid buildup, but as failures mount up it seems many are turning their eyes to the main competing hypothesis – that the disease is caused by aggregation of tau proteins.

In its statement AC Immune noted that the TAURIEL phase II trial of anti-tau drug RG-6100 in Alzheimer’s, run in partnership with Roche, will continue.

In December AC Immune also signed an $81 million deal with Eli Lilly – who were rebounding from several of their own failures in AD – to develop drugs targeting aggregation of tau proteins.

Meanwhile, crenezumab will continue to be studied in a Columbian trial in cognitively healthy individuals with an autosomal dominant mutation who are at risk of developing familial Alzheimer's disease, under the Alzheimer’s Prevention Initiative (API), which began in 2013.

This study will determine if treating people carrying this mutation prior to the onset of AD symptoms will slow or prevent the decline of cognitive and functional abilities.

Professor Andrea Pfeifer, CEO of AC Immune, said: “We are extremely disappointed about the outcome of the Phase III CREAD 1 interim analysis and we would also like to thank patients and caregivers for their participation. We continue to be optimistic about the potential future of crenezumab as we await the outcome of the Colombian API study to prevent AD symptoms in patients with familial AD to see if the antibody treatment may provide disease-modifying effects in patients with early-onset disease.

“We remain committed to our ongoing pre-clinical and clinical candidates targeting tau and neuro-inflammation to treat Alzheimer’s disease, neuro-orphan diseases and Parkinson’s disease, which are partnered with five leading pharmaceutical partners, including Roche’s subsidiary Genentech.”