February 2, 2010
Doctors may learn next month that Dimebon, a 27-year-old hay fever treatment and one of the most mysterious compounds yet tried to fight dementia, is poised to become their newest and perhaps best weapon against Alzheimer’s.
Medivation Inc., the start-up that persuaded Pfizer Inc., the world’s biggest drugmaker, to help develop Dimebon, may be ready to release new research data during the first week of March, said Bengt Winblad, head of Alzheimer’s research at the Karolinska Institute in Stockholm and a leader of the European trials for the product. The study may confirm a 2008 finding in Russia that patients functioned better and thought more clearly after swallowing Dimebon tablets three times a day.
The data augur a make-or-break moment for San Francisco- based Medivation, which has no products on the market and has recorded losses exceeding $150 million since 2003. Pfizer, which hasn’t brought a new drug to market that generates more than $1 billion a year since the pain pill Lyrica won U.S. clearance in 2004, has pinpointed Alzheimer’s as one of six focuses of research. Doctors say millions of patients may benefit.
The 183-patient Russian study, reported in the Lancet in July 2008, “showed the most effective and sustained benefit that we’ve ever seen in Alzheimer’s,” Samuel Gandy, associate director of the Alzheimer’s Disease Research Center at Mount Sinai School of Medicine in New York, said in a telephone interview. “There is nothing that’s currently approved that compares to it and nothing else really in the pipeline that compares to it.”
Some patients were better after taking the drug for 18 months than they were at the start of the trial, something never previously seen with the progressive disease. Gandy, who wasn’t involved in the research, said the drug stands to win approval even if the next study “is only half as good as the original.”
Few Alzheimer’s candidates beat the odds. There hasn’t been a new drug for the disease since Namenda, from New York-based Forest Laboratories Inc., was approved in 2003, and almost a dozen drugs in mid- to late-stage testing have failed since then, according to data compiled by Bloomberg.
Drugs that looked exciting in early studies have turned into disappointments, while others that appeared less promising ended up successful, said Constantine Lyketsos, chair of psychiatry at Johns Hopkins Bayview Medical Center in Baltimore.
“Ultimately with Dimebon, the data will speak,” Lyketsos said. “Even if it was hugely promising and exciting, it would be a little while before it ends up on the market. My patients and families need realistic hope at this point and I’m not sure that’s realistic hope at this point.”
Now valued at $1.13 billion, Medivation may plunge 35 percent in Nasdaq trading if the study fails, said Ian Sanderson, an analyst at Cowen & Co. in Boston. Success may propel the stock to rise 20 percent, he said. Sanderson rates the shares “neutral.” Seven other analysts say investors should buy Medivation and one has a “sell” opinion, according to Bloomberg data.
Medivation has risen 80 percent in Nasdaq Stock Market composite trading in the last 12 months as investors anticipate the study results. The shares advanced 1.6 percent yesterday, to $33.82.
Pfizer shares rose 29 percent in the past 12 months, and climbed 13 cents, to $18.79, in New York Stock Exchange composite trading.
Positive results would usher Dimebon into a $4 billion a year market that may almost triple by 2018, said Matthew Winton, an analyst at Decision Resources Inc. in Waltham, Massachusetts, in a telephone interview.
Analysts said they expect Medivation and New York-based Pfizer to file for regulatory approval of Dimebon in 2011. Results from the 525-patient Connection study could move that date forward, company officials said.
“We’re all very excited that we will reproduce exactly what was seen in the other trial,” said Briggs Morrison, senior vice president of Pfizer’s primary-care development group, in a telephone interview. “If that data comes together and in our conversations with regulators they feel that it’s a strong package worthy of filing, we all have a passion to get these important medicines to patients.”
In its initial studies, Dimebon was effective in all five areas examined and the improvements lasted longer than the effects seen in separate research on rival therapies. If the results are confirmed, the drug may generate at least $1.6 billion in annual sales by 2015, Sanderson said. The top spot in the market is now held by Pfizer and Tokyo-based Eisai Co.’s Aricept, which generates $2.5 billion a year.
Medivation acquired Dimebon, which has been used since 1983 to treat hay fever in the former Soviet Union, from a company formed by Sergey Bachurin, a researcher at the Institute of Psychologically Active Compounds, in Chemogolovka, Russia.
The drug was first identified as a possible way to protect neurons when the Russian Academy of Science, in Chernogolovka, Russia, started in the early 1990s to screen libraries of compounds for their ability to block a key brain receptor. Belief in the drug was bolstered when researchers found it improved learning in brain-damaged rodents.
If Dimebon beats the 70 percent failure rate seen in drug development, the results -- and clearances from the U.S. Food and Drug Administration and its European counterparts -- may arrive before scientists pinpoint how the product works.
What Patients Want
Investigators once thought Dimebon combined the activity seen with the two types of drugs already approved for Alzheimer’s disease: medicines such as Pfizer’s Aricept that increase levels of a brain chemical that helps transmit messages between nerves, and drugs such as Forest’s Namenda, that block the absorption of toxic levels of another neurotransmitter. Studies dispelled that hypothesis, and what Dimebon does inside the brain remains unknown.
Patients don’t care why a drug works -- only if it does.
“Many of my patients or their spouses say, ‘If I could at least keep my husband or wife as she is now, I would be very happy,’ ” said Karolinska’s Winblad. “In a way, that’s what you do with this drug. You prolong the time to the decline.”
Dimebon is one of five Alzheimer’s medicines that may reach the market in the next decade, Winton said. The drugs, including products from Johnson & Johnson in New Brunswick, New Jersey; Elan Corp. in Dublin; Pfizer; Baxter International Inc. in Deerfield, Illinois; and Eli Lilly & Co. in Indianapolis, may spur an $11 billion market by 2018 as prices and the number of patients climb, Winton said.
Most of the potential Dimebon competitors reduce levels of amyloid plaque, a substance that builds up in the brain of people with Alzheimer’s. The four approved drugs, which ease symptoms for as much as six months, generated $6.3 billion in the 12-months ended Sept. 30, according to IMS Health Inc., a research company in Norwalk, Connecticut.
Scientists have now focused on Dimebon’s effect on mitochondria, so-called power plants that generate energy in cells, with laboratory studies showing it improves cells’ function and helps them withstand stress.
“The data is really clear, but it is in cell culture,” Maria Ankarcrona, a Karolinska researcher, said in an interview. “Stressed cells respond more to Dimebon than normal cells.”
Alzheimer’s is a progressive disease that starts with mild forgetfulness and eventually robs patients of memories and independence. It afflicts 30 million people worldwide, a number that may exceed 100 million by 2050, according to Alzheimer’s Disease International, an advocacy group based in London.
Pfizer, with revenue of $48.3 billion in 2008, needs new medications to replace the sales it will lose when its biggest- selling drug, the cholesterol-lowering drug Lipitor, loses patent protection in 2011. The patent on Aricept expires at the end of this year.
Pfizer paid Medivation $225 million in September 2008 to help develop Dimebon for Alzheimer’s and Huntington’s disease, and may pay an additional $500 million as the drug proceeds through the regulatory process. Pfizer is covering 60 percent of the development costs in the U.S. and will get a like portion of the profits.
The Medivation development program includes five pivotal trials of Dimebon, for use alone and in combination with existing drugs, and for patients with disease ranging from mild to severe. The 183 volunteers in the first such study, in Russia, were given either Dimebon or a placebo for six months, while other anti-dementia drugs weren’t allowed.
The researchers evaluated the last patient enrolled in the 525-patient Connection study in December and are now starting to analyze the findings, Winblad said. The results should be available by early March, and Medivation and Pfizer may be able to release the findings by then, he said.
Pfizer’s Morrison and Medivation CEO David Hung said the data will be released by July.
“The Connection study is an important study, but it’s only one of a number of studies,” Hung said. “We have a lot of shots on goal.”
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