Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse

Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse, excellent Senior Journal article says

As seen at: www.seniorjournal.com 29 August 2010 AM Jerusalem time:

Alzheimer's, Dementia & Mental Health: Battle Against Alzheimer’s Disease Hits Wall as Drug Test Stopped; Maybe Plaque Not Cause seniorjournal.com

Note by Alexei Koudinov: Please make a visit to the original publication to appreciate this excellent report, thanks!

Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse

Aug. 19, 2010 – The efforts to prevent or successfully treat Alzheimer’s disease – the disease most feared by senior citizens - with drugs has never advanced very far, but these efforts suffered a major setback this week when Eli Lilly and Company announced it was halting development of semagacestat. This potential treatment for AD was in advanced clinical trials when it was discovered to be making patients worse instead of better. Many see this failure as a major blow to the most popular theory on the cause of the disease.

The Lilly announcement said, “Studies showed it did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.”

"This is disappointing news for the millions of Alzheimer's patients and their families worldwide who anxiously await a successful treatment for this devastating illness," said Jan M. Lundberg, Ph.D., Executive Vice President, Science and Technology, and President, Lilly Research Laboratories. "This is a setback, but Lilly's commitment to beating Alzheimer's will not waver."

Lilly is instructing clinical trial investigators for all semagacestat studies to contact study participants as soon as possible and tell them to immediately stop taking the study drug. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has also informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies.

In two pivotal Phase III trials, semagacestat was compared with placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease.

Semagacestat was designed to reduce the body's production of amyloid beta plaques, which scientists believe play an important role in causing Alzheimer's disease. Semagacestat is believed to block the activity of gamma secretase, an enzyme that is essential to the body's production of amyloid beta plaques, according to the company. It was being tested in two Phase III clinical trials called IDENTITY and IDENTITY-2.

Lilly’s interim analysis showed that, as expected, cognition and the ability to complete activities of daily living of placebo-treated patients worsened. However, by these same measures, patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo.

In addition, data showed semagacestat is associated with an increased risk of skin cancer compared with those who received placebo.

Semagacestat was one of many drugs being tested that focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease. Lilly actually has another amyloid-beta compound, solanezumab, in Phase III trials and says this testing will continue.

The company says these two compounds have “different mechanisms of action.” Lilly also has two other compounds in earlier stages of clinical development that will also continue.

Lilly's clinical team will continue to gather and evaluate data from these studies, and will publish the results for the benefit of future Alzheimer's research.

Although dosing with semagacestat is being stopped, Lilly plans to continue collecting safety data, including cognitive scores, for at least six months through regularly scheduled follow-up visits with study physicians and modifications of the existing Phase III protocols.

These additional follow-up visits are expected to help answer a number of important questions, including whether the differences between patients who received semagacestat and those who received placebo will continue after semagacestat has been discontinued. Other smaller short-term studies will be stopped and participants will receive appropriate follow-up.

"We are clearly disappointed by the results," said John C. Lechleiter Ph.D., Lilly's chairman and chief executive officer. He said, however, that the company has nearly 70 molecules currently in clinical development.

"Pharmaceutical research always carries risk, as these results show. But it offers as well the potential for tremendous reward for millions of patients who await new medicines. Despite this and other recent setbacks, Eli Lilly and Company remains financially strong and is even more determined to prevail in our quest to provide new treatments for Alzheimer's and other serious diseases," added Lechleiter.

About Alzheimer's disease

Alzheimer's disease is a fatal form of dementia that causes progressive decline in memory and other aspects of cognition. It occurs when billions of neurons in the brain begin dying prematurely. Researchers don't know exactly what causes it, but the leading hypothesis is that amyloid beta plaques play an important role.

About the IDENTITY trials

IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) and IDENTITY-2 are Lilly's Phase III placebo-controlled trials studying semagacestat, a gamma-secretase inhibitor being investigated as a potential treatment to slow the progression of mild to moderate Alzheimer's disease. Both Phase III trials are fully enrolled, with more than 2,600 patients from 31 countries, and include a treatment period of approximately 21 months. An open-label extension study (IDENTITY-XT) is available to all participants completing either study.

All study participants had to be at least 55 years old and meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease, with certain assessment scores indicating mild to moderate Alzheimer's disease. Patients with more advanced Alzheimer's disease were not included in the studies.

This article URL