- Johnson & Johnson's Janssen unit has pulled development of atabecestat, a BACE inhibitor in development to slow cognitive decline in people at risk for Alzheimer’s dementia, following a review of all available liver safety data.
- The company said some patients developed serious elevations of liver enzymes, leading Janssen to the conclusion "that the benefit-risk ratio is no longer favorable to continue development of atabecestat for people who have late-onset preclinical stage Alzheimer’s disease."
- Janssen has stopped screening, randomization and dosing in its Phase 2b/3 EARLY study in late-onset preclinical stage Alzheimer’s disease and in its Phase 2 long-term safety study.
The road to success in Alzheimer's disease therapy is strewn with failed drug development programs, and Janssen's atabecestat is yet another loss. The BACE inhibitor, which had made it as far as a Phase 2b/3 EARLY study in late-onset preclinical stage Alzheimer’s disease and in a Phase 2 long-term safety study, crashed out when patients developed serious elevations of liver enzymes.
This is another challenge for R&D in Alzheimer's, and potential another cross against the beta amyloid plaque theory. Over a year ago, Merck & Co terminated its Phase 3 EPOCH trial of verubecestat after an independent data monitoring committee stated that there would be "virtually no chance of finding a positive clinical effect." And almost exactly a year later, Merck discontinued its Phase 3 APECS study of verubecestat in very early stage Alzheimer's, after another independent committee stated that there was unlikely to be a positive risk/benefit profile.
Despite these challenges, the BACE inhibitors are one of the classes where developers are still holding out hope.
Biogen is developing its own in aducanumab. The company has tweaked its pair of Phase 3 studies, increasing enrollment to deal with "variability" in the primary endpoint, which hit the big biotech's shares. However, Biogen has twice cut its royalties to originator Neurimmune in return for payments, which underlines the company's confidence in the drug. AstraZeneca and Lilly's lanabecestat was given fast track designation from the Food and Drug Administration in August 2016, and Phase 3 results are expected in September 2019.
The Food and Drug Administration is pushing pharma to continue the clinical development of drugs in Alzheimer's disease with the issuance of five new guidance documents.