On June 12, Lilly/AstraZeneca announced the termination of the global phase III project for the treatment of Alzheimer’s disease with lanabecestat (oral BACE inhibitor). Lilly and AstraZeneca reached an alliance to develop lanabecestat in 2014. Lilly is mainly responsible for clinical development work. AstraZeneca is mainly responsible for pharmaceutical production.
The decision of both parties was not based on the safety aspect of lanabecestat, but the independent data monitoring committee (IDMC) believes after evaluating the clinical results. Whether it is the AMARANTH study conducted in patients with early AD or the DAYBREAK-ALZ study conducted in patients with mild Alzheimer’s dementia, lanabecestat did not reach the primary efficacy endpoint. Therefore, the company is advised to stop the study in order to avoid futile efforts. The AMARANTH extension study also stopped.
Lanabecestat is also a stage III clinical Alzheimer’s disease project following the catastrophic phase III failure of solanezumab (Aβ inhibitor) at the end of 2016. The defeated giant was more than Lilly. Johnson also announced on May 18 that it had stopped phase II/III studies of the BACE inhibitor atapecestat. However, the reason for Johnson & Johnson’s decisive suspension of its research was the observation of severe liver enzyme elevations, and the benefits of the drug itself – the risk is not ideal. The Merck East declared its abandonment of development to verubecestat that had already reached Phase III as early as February 2017.
In fact, both BACE and Aβ targets are hard-hit areas for Alheimer’s disease. As shown in the following figure, there are 28 BACE inhibitor projects in the world. There are 28 BACE inhibitor projects in the world, and 21 of them have been declared failure (the status of the database is Inactive), and large and small pharmaceutical giants can be seen everywhere. There are two other long-term reports (the status of the database tag is Unknown). The failure rate of the entire BACE target is as high as 82%. At present, in the BACE field, the remaining mid-to-late project is left with 100 healthy/elenbecestat (phase III), Amgen/Novartis CNP520 (phase II/III), and Lilly’s LY3202626 (phase II).
Meenas Pangalos, executive vice president of IMED Biotech division of AstraZeneca, said: “We are disappointed with this result. Our science is working day and night and we are looking forward to finding an effective treatment for Alzheimer’s patients. Still, we hope that our work will provide more inspiration for overcoming this stubborn disease.”
Daniel Skovronsky, Lilly Research Laboratory Director, said: “The complexity of Alzheimer’s disease itself has made this disease one of the most difficult problems to overcome today. We feel sorry for millions of patients suffering from this disease. We are grateful to all participants in the clinical study of Lanabecestat. Lilly has invested a lot of energy in Alzheimer’s disease drug development over the past 30 years and we will not abandon the search for effective treatments for these patients.”