Anti-amyloid beta antibodies in development at Eli Lilly and Roche have failed to improve outcomes in a phase 2/3 Alzheimer’s disease trial. Despite the setback, Roche is continuing two phase 3 trials of its asset in a broader population of Alzheimer’s patients.
The failed phase 2/3 study was sponsored by Washington University School of Medicine with support from groups including Lilly and Roche. Investigators randomized 194 people with an early-onset, inherited form of Alzheimer’s to take either Lilly’s solanezumab, Roche’s gantenerumab or placebo and tracked them for up to seven years.
Based on the top-line findings, neither drug is effective in dominantly inherited Alzheimer's disease (DIAD). The primary endpoint tracked cognition annually for four years using four tests of early-stage disease, the results of which were combined to give a composite score.
Neither gantenerumab nor solanezumab slowed the decline in the composite cognitive score enough for the clinical trial to hit its primary endpoint. Researchers are still analyzing secondary endpoints and biomarkers ahead of the planned presentation of the data at an event in April.
While those analyses are ongoing, Lilly has already seen enough data to say it has no plans to seek approval in the subpopulation of DIAD patients enrolled in the phase 2/3. Solanezumab has already failed in the broader Alzheimer’s population, leading Lilly to give up on the asset in 2016.
Roche remains more committed to gantenerumab, despite it failing a phase 3 trial in 2014. The Swiss pharma resurrected gantenerumab in 2017 and is now running two more phase 3 trials.
In the face of the failure in DIAD patients, Roche talked up the differences between the phase 2/3 flop and its ongoing late-phase studies to explain its continued confidence that gantenerumab may succeed. Levi Garraway, chief medical officer at Roche, said in a statement that the phase 2/3 failure “does not reduce our confidence in the ongoing phase 3 GRADUATE clinical program.” Garraway also said it is impossible to draw firm conclusions from the phase 2/3 trial.
Outside observers took a different position. Analysts at Jefferies expected the phase 2/3 trial to fail and accepted that the small size of the study and initial use of potentially suboptimal doses may have contributed to the lackluster data. Even so, the analysts said the failure “again suggests the ongoing gantenerumab phase 3 studies are high risk.”
Roche is set to find out whether that risk has paid off when it posts data from the phase 3 program in 2022. The program is assessing whether increasing the gantenerumab dose above the level used in earlier, failed trials will lead to better outcomes.
The news today also hit Biogen, which is working on a similar AD approach, and is set to re-file its once failed (and now re-born) aducanumab any day now. Shares in the Big Biotech were down nearly 2% in early trading on the Roche and Lilly update.