Lundbeck has acknowledged that the Alzheimer’s candidate idalopirdine, being developed through a partnership with Otsuka Pharmaceutical, has failed its first Phase III trial by failing to show efficacy in patients with mild to moderate forms of the disease.
Both dosages of idalopirdine used in the STARSHINE trial missed the study’s primary endpoint of a reduction in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score when added to donepezil.
The drug also missed STARSHINE’s secondary endpoints by failing to show significant improvement over placebo, Lundbeck said, adding that the drug was safe and well tolerated. The company announced topline results but did not disclose detailed data.
The results contrasted with positive Phase II results reported in 2013 for the candidate in combination with donepezil for 24 weeks.
“The phase II data were very encouraging but unfortunately, these [Phase III STARSHINE] data failed to replicate those findings,” Anders Gersel Pedersen, M.D., DM.Sc., Ph.D., Lundbeck evp and CSO, said in a statement. “We are disappointed about the outcome of this study.”
Lundbeck said it would continue two additional Phase III trials of idalopirdine, STARBEAM and STARBRIGHT. Data from both studies is expected to be reported in the first quarter of 2017.
Lundbeck has developed idalopirdine through a collaboration with Otsuka.
Idalopirdine, also called Lu AE58054, is a selective antagonist of the 5-hydroxytryptamine type 6 (5-HT6) receptor, expressed in brain regions involved in cognition, such as the cortex and the hippocampus, and modulates activity of multiple neurotransmitter systems. Idalopirdine is believed to work by modulating the balance between excitation (glutamate) and inhibition (gamma-aminobutyric acid, or GABA) in the brain.
In July, idalopirdine was granted the FDA’s Fast Track Designation.
Lundbeck and Otsuka are among drug developers that have sought to treat Alzheimer’s by developing serotonin receptors. Axovant Sciences is developing intepirdine (RVT-101), now the subject of the Phase III MINDSET trial in mild to moderate Alzheimer’s patients taking donepezil. But in February, Pfizer acknowledged it had ended development of PF-05212377 (SAM-760), 4 months after discontinuing a Phase II trial.