Lilly Halts Development of Semagacestat for Alzheimer's Disease

Eli Lilly and CompanyEli Lilly and Company (NYSE: LLY) will halt development of semagacestat, a gamma secretase inhibitor being studied as a potential treatment for Alzheimer's disease, because preliminary results from two ongoing long-term Phase III 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.

The company's decision does not affect the ongoing clinical trials of solanezumab, Lilly's other compound in Phase III trials as a potential Alzheimer's treatment. While both drugs focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease, they have different mechanisms of action. Lilly also has two other compounds in earlier stages of clinical development; those studies are not affected by today's announcement.

In two pivotal Phase III trials, semagacestat was compared with placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease. Lilly has now reviewed data from a pre-planned interim analysis of semagacestat studies. This 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.

"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 they have received. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has appropriately informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies.

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 will help to 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.

The decision to halt development of semagacestat is expected to result in a third-quarter charge to earnings of approximately $.03 to $.04 per share. The company confirmed its previous 2010 earnings per share guidance range of $4.44 to $4.59 on a reported basis, or $4.50 to $4.65 on a non-GAAP basis.

"We are clearly disappointed by the results we are announcing today. However, Lilly's innovation strategy, based on advancing a pipeline of nearly 70 molecules currently in clinical development, does not rest on the success or failure of any single compound," said John C. Lechleiter Ph.D., Lilly's chairman and chief executive officer. "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."

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 semagacestat
Semagacestat is an oral agent 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. The compound's safety and efficacy are being tested in two Phase III clinical trials called IDENTITY and IDENTITY-2.

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.

Use of approved treatments for Alzheimer's disease (including donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne, RazadyneER), tacrine (Cognex) and memantine (Namenda)) is permitted during the study, provided that such medications had been given for at least 4 months and the dose had been unchanged for 2 months before study participants first received their study drug.

The primary objective of both IDENTITY trials was to determine whether semagacestat given orally would slow the decline associated with Alzheimer 's disease as compared with placebo. The study protocol calls for this to be evaluated periodically for 21 months after initiation of treatment for most patients. A participant's cognition and function are assessed using two 2 co-primary endpoints:

  • the Alzheimer's disease Assessment Scale - Cognitive subscore (referred to as the ADAS-Cog11); and
  • the Alzheimer's disease Cooperative Study - Activities of Daily Living Inventory (Referred to as the ADCS-ADL).

About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

Most Popular Now

Sanofi and GSK sign agreements with the Government…

Sanofi and GSK have signed agreements with the Government of Canada for the supply of up to 72 million doses of an adjuvanted COVID-19 vaccine, beginning in 2021. Thom...

Johnson & Johnson initiates pivotal global Pha…

Johnson & Johnson (NYSE: JNJ) (the Company) announced the launch of its large-scale, pivotal, multi-country Phase 3 trial (ENSEMBLE) for its COVID-19 vaccine candidate, J...

Scientists trace severe COVID-19 to faulty genes a…

More than 10 percent of young and healthy people who develop severe COVID-19 have misguided antibodies that attack not the virus, but the immune system itself, new resear...

Johns Hopkins researchers publish COVID-19 'predic…

Using a combination of demographic and clinical data gathered from seven weeks of COVID-19 patient care early in the coronavirus pandemic, Johns Hopkins researchers today...

Researchers uncover early results about an existin…

While scientists race to develop and test a vaccine effective against SARS-CoV-2, the virus that causes COVID-19, recent studies have indicated that countries with widesp...

Web resources bring new insight into COVID-19

Researchers around the world are a step closer to a better understanding of the intricacies of COVID-19 thanks to two new web resources developed by investigators at Bayl...

BioNTech and Pfizer initiate rolling submission to…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced the initiation of a rolling submission to the European Medicines Agency (EMA) for BNT162b2, the lea...

Boost for global response to COVID-19 as economies…

64 higher income economies have joined the COVAX Facility, a global initiative that brings together governments and manufacturers to ensure eventual COVID-19 vaccines rea...

COVID-19 vaccine AZD1222 clinical trial resumed in…

The Phase I/II clinical trial for the COVID-19 vaccine AZD1222 has resumed in Japan after discussion with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). ...

Vir Biotechnology and GSK announce global expansio…

Vir Biotechnology, Inc. (Nasdaq: VIR) and GlaxoSmithKline plc (LSE/NYSE: GSK) announced the global expansion to Phase 3 of the COMET-ICE (COVID-19 Monoclonal antibody Eff...

Johnson & Johnson announces European Commissio…

Johnson & Johnson (NYSE: JNJ) (the Company) announced the European Commission (EC), acting on behalf of the European Union (EU) Member States, has approved an Advance Pur...

Adequate levels of vitamin D reduces complications…

Hospitalized COVID-19 patients who were vitamin D sufficient, with a blood level of 25-hydroxyvitamin D of at least 30 ng/mL (a measure of vitamin D status), had a signif...