Pfizer/Janssen Kill Bapi Development for Alzheimer’s
Aaaand, it’s over. Yesterday (after the bell), Pfizer and Janssen announced the discontinuation of their development program for IV bapineuzumab, the anti-amyloid MAb for Alzheimer disease on which many high and low expectations were placed. It appears that the low expectations (expressed, in particular, at this blog) were accurate. The phase 3 efficacy results for the MAb in noncarriers of the AD risk allele APOE ε4 were negative, in addition to the recently announced negative phase 3 results for APOE ε4 carriers. Consequently the whole program has been scrapped, including any extension studies and 2 other ongoing phase 3 trials.*
Pfizer says that the results of the negative phase 3 studies will be presented at the upcoming EFNS meeting in Stockholm. What to look for: the degree to which bapineuzumab cleared brain amyloid (via PET imaging) and safety issues, specifically the incidence of ARIA. According to the press release, the most commonly observed serious AEs with bapineuzumab (ie, more common than with placebo and at a frequency of at least 1%) included ARIA-E (eg, vasogenic edema). Pfizer has told inquiring news sources that there are no plans to study bapineuzumab in earlier phases of AD (ie, MCI), but the option (if it’s ever picked up) rests on the safety of the MAb in the completed phase 3 trials in AD.
As far as I can tell, Pfizer/Janssen’s only other viable joint candidate for AD treatment is an anti-amyloid vaccine, ACC-001, which is in phase 2 development. Given that there’s now very slim hope for the clinical success of an anti-amyloid treatment in established AD (despite the fact that bapineuzumab appeared to remove amyloid from the brain), companies currently invested in the therapeutic strategy (for instance, Roche and GSK, along with Pfizer and Janssen) must seriously reassess their commitments. Roche’s crenezumab was recently selected for testing in a Colombian family with a deterministic gene for AD, so the study population here appears to be more promising. GSK’s candidate drug is (I believe) in phase 1 development. The phase 3 results for Lilly’s solanezumab in AD are, of course, expected imminently, and the chance of success, although very low, is not zero. Lilly’s MAb may target a more toxic version of amyloid (ie, soluble amyloid) than bapineuzumab (which was believed to be more specific for sequestered, insoluble amyloid in neuritic plaques). But that explanation may be more marketing than science.
* Although an imaging study with SQ bapineuzumab continues.
AEs = adverse events; ARIA = amyloid-related imaging abnormalities; MAb = monoclonal antibody; MCI = mild cognitive impairment; PET = positron emission tomography.