Lilly presents data on failed Alzheimer’s candidate
pharmafile | July 21, 2011 | News story | Research and Development | Alzheimer's disease, lilly, research and development news, semagacestat
Lilly has presented a review of data from semagacestat, the Alzheimer’s drug it dropped last year after disappointing results.
Phase II trials were halted in August 2010 when early signs suggested that semagacestat did not slow Alzheimer’s disease progression, but in fact made the patients’ condition worse.
To help understand what was happening, Lilly continued to gather data for another 32 weeks after dosing was stopped.
Lilly presented the data during a plenary session at the Alzheimer’s Association International Conference 2011 in Paris. It is unusual for companies to highlight data from failed projects, but Lilly says lessons learned from semagacestat’s failure could help Alzheimer’s research, which has been dogged by many setbacks.
Semagacestat was an oral agent designed to reduce the body’s production of beta-amyloid, which is believed to play a key role in causing Alzheimer’s. Semagacestat was believed to work by blocking gamma secretase, an enzyme essential to the body’s production of beta-amyloid.
The theory was that by blocking gamma secretase, this would in turn block production of beta-amyloid, and alleviate or even reverse some Alzheimer’s symptoms. But the opposite happened, with patients experiencing an accelerated decline in cognition and their ability to perform their normal daily activities.
Lilly continued to monitor these patients for seven months after they stopped taking the drug, to see if their accelerated decline would stop, or even be reversed compared to those who had been on placebo. The follow-up study found the cognitive and functional decline compared to patients on a placebo remained, but did not worsen.
Lilly did not put forward its own conclusions, but the results seem to confirm that gamma secretase inhibitiors are not the way forward – and also confirm that theories about what causes Alzheimer’s remain incomplete.
Many researchers still believe that beta-amyloid protein plays an important role in the disease, but evidence from this trial and others suggest the mechanism of Alzheimer’s disease is more complicated than originally hoped.
The findings are particularly important as a number of other companies have been developing gamma secretase inhibitors, including Bristol-Myers Squibb and its BMS708163 currently in phase II trials.
“When we made the decision to halt dosing in the trials, we committed to collecting this data in an effort to benefit future Alzheimer’s research and to provide safety follow-up for the patients,” said Dr Eric Siemers, enior medical director for the Alzheimer’s Disease Team at Lilly. “We have a great deal of appreciation and respect for the dedication of the patients and caregivers who remained committed to the semagacestat trials from the beginning until these follow-up data were collected. By obtaining this information, future research efforts can be guided much more effectively.”
“Although today we focused on what happened with semagacestat, the broader important point is that Lilly remains committed to Alzheimer’s research and the Alzheimer’s disease community,” said Dr Siemers. “We continue to move forward with the development of other molecules in our pipeline aimed at slowing the progression of Alzheimer’s disease.”
Andrew McConaghie
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