Lilly has decided to give up on an orally delivered Alzheimer's disease drug in late-stage clinical development due to disappointing preliminary results from two long-term phase III studies.
A pre-planned interim analysis of the data showed that semagacestat, which is designed to inhibit an enzyme called gamma sceretase involved in the body's production of amyloid beta plaques, failed to slow disease progression and in fact worsened clinical measures of cognition and the ability to perform activities of daily living in Alzheimer's disease patients.
The two phase III trials of semagacestat, which began in 2008, enrolled more than 2,600 patients with mild-to-moderate Alzheimer's disease. As would be expected due to disease progression, subjects showed a decline in cognition and the ability to complete activities of daily living during the course of the research. However, those taking semagacestat worsened to a statistically significantly greater degree than those treated with placebo.
The studies, known as IDENTITY and IDENTITY-2, also showed that semagacestat is linked to an increased risk of skin cancer.
Study subjects are being told to immediately stop taking the drug, although Lilly will continue collecting data, including cognitive scores, for at least another six months in an attempt to determine whether the differences between patients in the active drug and placebo groups will persist after semagacestat has been discontinued.
Lilly stressed that phase III studies of its other late-stage drug candidate for Alzheimer's, solanezumab, will continue unaffected by the failure of semagacestat. The drugs are similar in that they both focus on amyloid-beta proteins, but they have different mechanisms of action.
However, the failure of the semagacestat trials builds on a worrying trend for drugs designed to reduce production of amyloid beta plaques. For example, a 2008 study published in The Lancet showed that an experimental vaccine was able to clear subjects of amyloid plaques and yet had no significant effect on their dementia, leading some researchers to believe that the entire approach is misguided.
The decision to stop development of solanezumab also affects Elan, which was a partner on the drug and was entitled to compromotion rights and royalties.
Only days ago, Elan announced its own disappointing results for another Alzheimer's drug targeting amyloid plaques that the company is developing with Transition Therapeutics. Topline summary results of a phase II study for that drug, known as ELND005, showed that it did not achieve significance on cognitive and functional primary outcome measures. However, the partners have decided to go forward with phase III studies "based on the preponderance of evidence, and input from the experts in this field," Elan reported.
Stopping development of semagacestat is likely to result in a third-quarter charge to Lilly's earnings of around $.03 to $.04 per share but will not affect previous 2010 earnings per share guidance range of $4.44 to $4.59, Lilly said.
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