Boehringer Ingelheim has scrapped plans to develop its PDE9 inhibitor in Alzheimer’s after the drug flopped in phase 2. BI 409306 failed to show superiority over placebo in cognition across a midphase program that enrolled 457 patients with early signs of Alzheimer’s.
Germany’s Boehringer is yet to share a look at top-line data from the two phase 2 studies, saying only that the studies failed to meet their efficacy endpoints. Whatever Boehringer saw when it pooled the results for analysis was bad enough to cause it to drop plans to further develop the drug as a treatment for Alzheimer’s.
Researchers at Boehringer and beyond, attracted by animal data on synaptic plasticity and memory, have explored whether inhibiting different families of PDE enzyme can improve cognition. Some of these projects, such as Tetra’s PDE4 drug BPN14770, are still moving forward. But the failure of BI 409306 raises the risk PDE inhibition will join the long list of thwarted attempts to treat the disease.
Boehringer framed the setback as part and parcel of CNS drug development.
“This is what research is about: disappointments are a daily experience in science, but even these clinical trial results will add to the understanding of brain function and contribute to future progress in this area,” Jan Poth, Ph.D., therapeutic area head CNS diseases at Boehringer, said in a statement.
The collapse of the PDE9 Alzheimer’s program still leaves Boehringer with other therapeutic avenues in CNS to explore. Phase 2 trials of BI 409306 in people with schizophrenia or attenuated psychosis syndrome are currently enrolling. And Boehringer is running a 585-person, midphase Alzheimer’s trial of GlyT1 inhibitor BI 425809 in the hope its route to the glutamatergic circuit proves more effective than that of BI 409306. Boehringer expects to wrap up the BI 425809 trial in 2020.