Dr. Weeks Comment: In medical school, Dr. George Wolf told me once “Brad, when a new drug hits the market, use as much of it as you can…. while it is still available. ” He was making a humorous comment on the fact that so many drugs are rushed to market in a situation where corporate greed and corrupt bureaucratic rubber stampers push aside scientific integrity and ethical prudence (remember the foundation law of responsible medicine: “Primum Non Nocere First do no Harm” . The most recent debacle comes to us from Ely Lilly whose Alzheimer drug made people’s cognitive function worse and gave them higher rates of skin cancer to boot…. oops! (Any consequences to Lilly aside from stock price falling? Doubt it…)
Lilly Stops Alzheimer’s Drug Trials
By DUFF WILSON
Published: August 17, 2010
Eli Lilly halted two late-stage clinical trials of an experimental Alzheimer’s treatment on Tuesday, representing a setback to one leading theory on treating the degenerative disease and a new blow to Lilly’s business prospects.
The company said patients who had taken the drug, intended to reduce plaque in the brain, actually showed worse cognitive functioning and less ability to perform daily living tasks than patients who had taken a placebo.
“A completely unexpected result,” Dr. Eric R. Siemers, medical director for the Alzheimer’s team at Lilly, said in an interview. The patients also had a higher risk of skin cancer. The trials involving the drug, semagacestat, began in 2008.
The price of shares in the company, which is based in Indianapolis, has fallen 5 percent in the last week, as Lilly has had problems involving some of its most popular drugs.
Lilly officials said that they would still follow the more than 2,600 Alzheimer’s patients in 31 countries who were enrolled in the trials for six more months. The company is conducting a separate test of a biologic therapy aimed at Alzheimer’s.
Dr. Ronald C. Petersen, director of the Alzheimer’s Disease Research Center at the Mayo Clinic in Rochester, Minn., and a member of the executive committee of the Alzheimer’s Association, said the drug failure highlighted the need to try to attack multiple targets related to dementia, not just plaque on the brain. He compared the approach to developing several drugs for hypertension.
“When one like this fails, it’s discouraging to the field, but it’s not the end of the day,” Dr. Petersen, who was not involved with the trials, said in an interview. “We have other targets out there and other ways to attack the same target.”
Still, Lilly’s announcement quashed one hope, and an effective prevention or cure, if possible, remains years away.
While hundreds of drugs are under study, Lilly’s effort was one of only five to reach late-stage clinical trials, said Dr. Paul S. Aisen, director of the federally financed Alzheimer’s Disease Cooperative Study and a professor of neuroscience at the University of California, San Diego.
“It is a significant disappointment,” he said, “but there’s still a lot to be optimistic about.”
Dr. Aisen, who also consults widely for the drug industry, said he was excited about brain scans and spinal fluid tests that may help to identify people most at risk of Alzheimer’s before they show any symptoms ”” the time a treatment may be most effective.
Lilly shares fell 2.3 percent to $34.75 on Tuesday, the latest of several blows to the company. Lilly said it would charge 3 cents to 4 cents a share against third-quarter earnings for the Alzheimer’s test failure but reaffirmed earlier guidance for 2010 profits.
“We are clearly disappointed by the results we are announcing today,” John C. Lechleiter, Lilly’s chairman, said in a statement. “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.”
Lilly’s failure in the final phase of an Alzheimer’s trial follows misses by Myriad Genetics and by the team of Pfizer and Medivation. Another closely watched drug being developed by Pfizer, Johnson & Johnson and Elan has had mixed results in a middle-stage clinical trial. Several prescription drugs are approved to treat symptoms of Alzheimer’s, but none stop its progression.
Lilly’s drug was intended to reduce production of so-called amyloid beta plaques in the brain by inhibiting the activity of an enzyme called gamma secretase.
Dr. Siemers of Lilly said the failed trials might indicate that too much reduction in amyloid beta unexpectedly harms cognitive functions, or it may be that the problems arose from the drug’s effect on some 20 other proteins.
“It’s certainly a setback, but no one’s developed a treatment to slow the rate of progression of the disease,” Dr. Siemers said. “This was I think a very good shot on goal, but not Lilly’s only potential treatment.”
Lilly is also testing an intravenous monoclonal antibody that reduces amyloid beta, the plaque, by a different and more focused mechanism in late-stage clinical trials. “They’re actually going quite well,” Dr. Siemers said of those trials.
Alzheimer’s affects an estimated 5.3 million Americans. Dr. Steven T. DeKosky, an Alzheimer’s researcher and dean of the University of Virginia‘s School of Medicine, said Lilly’s failure may show that plaque reduction does not help patients with full-blown symptoms but it could still help to prevent the disease.
“It’s too soon to say,” said Dr. DeKosky, who has consulted for Lilly and other companies. “Having the drug fail doesn’t say the hypothesis is wrong that amyloid causes the disease.” Some researchers are less certain about the role that plaque may play in the onset of the disease.
Ending the trial was not the only disappointing news Lilly received on Tuesday. The Food and Drug Administration released a critical staff review of the company’s application to market its blockbuster antidepressant Cymbalta for the treatment of chronic pain.
The review, to be considered by an F.D.A. advisory committee on Thursday, questioned Lilly’s statistical methods and the risks of liver toxicity. Cymbalta, Lilly’s second-best-selling drug behind Zyprexa, is approved for major depression, anxiety, diabetic pain and fibromyalgia, but Lilly is seeking a vast new market in chronic pain.
Seamus Fernandez, a Leerink Swann analyst, said in an investor note that the F.D.A. staff report still showed a likelihood of expanding the Cymbalta label to include chronic pain. As for the Alzheimer’s setback, he said by e-mail, “It was a big upside opportunity ”” very high risk, high reward ”” this was basically Lilly swinging for the fences.”
Last Thursday, the company lost a court ruling on patent protection for its attention-deficit drug Strattera. Last month, it lost an appellate court decision on a patent for the cancer drug Gemzar. And in the last year, sales have been disappointing for the blood thinner Effient, Lilly’s first new product in five years.
Mark Taylor, a spokesman, said Lilly was still optimistic about Effient. But another competitor looms in the $6 billion anticoagulant market: Brilinta from AstraZeneca is expected to be approved by the F.D.A. by Sept. 16.
Lilly is already facing the biggest “patent cliff” in the industry. Five of its six leading products face generic competition in the next four years. Barbara Ryan, a stock analyst with Deutsche Bank, said Lilly’s earnings will decline 35 percent by 2014 unless it makes one of the larger acquisitions it has historically resisted.
“Each individual issue is not necessarily all that significant, but collectively Lilly faces a real uphill battle because they face a significant amount of generic competition over the next several years and they are making a singular bet on their pipeline,” Ms. Ryan said in an interview. “And the news hasn’t been very good.”
Andrew Pollack contributed reporting.