The worsening of cognitive symptoms in patients taking a now-shelved Eli Lilly experimental Alzheimers compound wasnt reversed even seven months after the end of treatment, according to new data presented today at the Alzheimers Association International Conference in Paris. The data raise questions about the efficacy and safety of the many others in the same class of drug that are still being developed.
Semagacestat aimed to slow or reverse the progression of Alzheimers disease by inhibiting an enzyme called gamma secretase, which is important to building a sticky substance called amyloid that can clump in the brain. Amyloid is thought to be one of the major contributors to Alzheimers disease.
Bristol-Myers Squibb and other companies also have gamma secretase inhibitors in development. Some phase II data is expected tomorrow from Bristol.
Lillys gamma secretase inhibitor was the furthest along in development when the company announced last year that some analyses of its late-stage clinical trial data indicated that patients in the experimental treatment group fared worse on cognitive symptoms than those taking a placebo. Patients taking the compound also seemed have an increased rate of skin cancer.
Based on that information, Lilly halted the trial and scrapped the compound.
The new data are from follow-up of those clinical-trial patients 32 weeks after they received the last dose of drug last August. In a packed, cavernous conference room at AAIC, Eric Siemers, Lillys senior medical director for Alzheimers disease, showed analyses indicating that the experimental groups cognitive problems didnt reverse after the drug was stopped though they didnt continue to decline at a faster-than-usual rate, either. After seven months, the participants symptoms hadnt returned to baseline or recovered to match the placebo group.
The plateau in cognitive decline suggests that the drug may affect proteins that benefit or are necessary to the brains functioning, though more research is needed, Siemers tells the Health Blog.
As for what this means for other gamma secretase inhibitors, its hard to say, he says. For instance, some others in development are focused on more selectively acting on the target, while others are looking to modulate the enzymes effect rather than block it entirely, he says. But because of these data, the hurdles been raised for the future development of the compounds, says Siemers.
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