UCB's Alzheimer's drug misses Phase 2 goal, shows positive secondary outcomes

On Thursday, UCB announced that a Phase 2 trial for its anti-tau Alzheimer’s treatment, bepranemab, did not achieve its main goal. The study revealed that neither the low dose nor the high dose of the drug produced significant benefits for patients. The assessment was based on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score, which measures cognitive and functional changes over a period of 80 weeks. UCB mentioned it is currently considering the next steps, though specific plans were not disclosed.

Despite the setback in the primary endpoint, UCB pointed out some positive outcomes concerning secondary endpoints, particularly in cognitive measurements. Both doses of bepranemab demonstrated improvements in cognition when compared to a placebo, as measured by the ADAS-Cog14 scale. These improvements were deemed "nominally significant" by a UCB spokesperson.

Specifically, patients who received the low dose of bepranemab experienced a 25.2% improvement over their baseline scores compared to the placebo group, with a p-value of 0.0197. Those on the high dose saw a 21.4% improvement, with a p-value of 0.0485. The drug was administered every four weeks over the 80-week duration of the study.

Additionally, the study noted that both dosage levels of bepranemab reduced the accumulation rate of tau protein in certain brain regions. The low-dose group saw a reduction of 58.3%, while the high-dose group observed a 50% reduction.

It remains uncertain which endpoint UCB might prioritize if it decides to proceed to a pivotal study for bepranemab. Both Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla, which are already approved, utilized the CDR-SB as their primary endpoint but also included various forms of the ADAS-Cog as secondary measures. These approved drugs showed statistically significant improvements across all endpoints.

The findings from the bepranemab study were presented at the Clinical Trials on Alzheimer’s Disease annual meeting in Madrid. UCB plans to release further data, including detailed results on the CDR-SB score changes, in early 2025.

This announcement follows a recent decision by Roche and Genentech to terminate their collaboration with UCB on this program. Back in 2020, Roche and Genentech had made an initial payment of $120 million and committed up to $2 billion in potential milestones and royalties. However, as of October 22, they returned the global rights of the program to UCB.

While there have been successful approvals for anti-amyloid antibodies like Leqembi and Kisunla, developing effective tau-targeting drugs has proven more challenging. Multiple tau-targeting antibodies have failed in clinical trials, including Biogen’s gosuranemab, Lilly’s zagotenemab, and AC Immune’s semorinemab, which had mixed results in their Phase 2 trials.