Findings to Be Presented at American Society of Clinical Oncology’s Genitourinary Cancers Symposium

SAN FRANCISCO, CA and TOKYO–(Marketwire – February 15, 2011) -  Medivation, Inc. (NASDAQ: MDVN) and Astellas Pharma Inc. today announced positive, new, long-term follow-up data from the Phase 1-2 trial of MDV3100 in patients with advanced prostate cancer. MDV3100 is a novel, triple-acting, oral androgen receptor antagonist. These new results showed that MDV3100 continues to show durable antitumor activity as evaluated by median times to prostate-specific antigen (PSA) progression and radiographic progression. These findings confirm the initial Phase 1-2 results published in The Lancet, in which MDV3100 consistently demonstrated anti-tumor activity in both chemotherapy-naïve and post-chemotherapy patients across endpoints, as evaluated by PSA levels, radiographic findings and circulating tumor cell (CTC) counts.

“We are very encouraged by these promising new, long-term efficacy findings, which continue to demonstrate the antitumor activity of MDV3100 and give us confidence that MDV3100 has the potential to benefit patients with advanced prostate cancer,” said Lynn Seely, M.D., chief medical officer of Medivation.

Long-Term Follow-Up Results
A total of 140 men with progressive disease were enrolled in the Phase 1-2 trial between July 2007 and December 2008. Of those, 18 remained on active treatment (16 chemotherapy-naive and 2 post-chemotherapy) at the time of this analysis.

PSA progression data were calculated using three distinct reporting criteria: the criteria specified in the Phase 1-2 trial protocol; the most recent published PSA reporting consensus criteria (the Prostate Cancer Clinical Trials Working Group 2, or PCWG2, criteria)1; and an older commonly used reporting method (the Prostate-Specific Antigen Working Group 1, or PSAWG1, criteria)2.

Median times to PSA progression presented in the poster are as follows:

Time to PSA Progression   Chemotherapy-Naïve
(n=65)   Post-Chemotherapy
(n=75)
Per-protocol criteria   Not reached

316 days (45 weeks)
PCWG2 criteria

281 days (40 weeks)    148 days (21 weeks)
PSAWG1 criteria   420 days (60 weeks) *
812 days (116 weeks) **    166 days (24 weeks)

*All chemotherapy-naïve patients
**Subpopulation of chemotherapy-naïve patients who were also ketoconazole-naïve

The protocol-specified criteria define PSA progression as a 25% increase in PSA from starting baseline, provided that the increase is at least 5 ng/mL. This is the most liberal approach, and will produce the longest times to progression. The PCWG2 criteria define PSA progression as a 25% increase in PSA from nadir (i.e., from the lowest level of PSA attained by the patient on study), provided that the increase is at least 2 ng/mL. Under the PSAWG1 criteria, PSA progression requires: a 50% increase in PSA above nadir for patients who experienced a PSA decline of 50% on treatment; a 25% increase in PSA above nadir for patients who experienced a PSA decline < 50% on treatment; and a 25% increase in PSA above starting baseline for patients who did not experience any PSA decline on treatment; provided in each case that the PSA increase was at least 5 ng/mL. This is an intermediate approach to defining PSA progression, producing times to progression between those produced using the other two approaches.

The median times to radiographic progression presented in the poster are as follows:

Chemotherapy-Naïve
(n=65)   Post-Chemotherapy
(n=75)
392 days (56 weeks)    175 days (25 weeks)

Circulating tumor cell counts were available for 128 of 140 patients. Of those, 70 of 77 (91%) who had favorable pre-treatment counts ( < 5 cells/7.5 mL blood) remained favorable post-treatment, and 25 of 51 patients (49%) converted from unfavorable pre-treatment counts to favorable post-treatment counts.

“These positive long-term findings in both chemotherapy-naïve and post-chemotherapy advanced prostate cancer patients provide further support for our expanded development program into earlier-stage prostate cancer patients,” said Steven Ryder, M.D., president, Astellas Pharma Global Development. “In addition to the ongoing Phase 3 PREVAIL trial, which is currently enrolling men with advanced prostate cancer who are chemotherapy-naïve, we and our partner Medivation plan to initiate two Phase 2 trials in earlier-stage prostate cancer in the first half of this year.”

The new long-term follow-up findings will be presented in a poster session at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium (ASCO-GU) in Orlando, Fla. on Thursday, February 17 (poster board #A71). The poster will include the most up-to-date data from the trial and will expand upon the results originally submitted in the abstract. The abstract (#177), titled “Antitumor activity of MDV3100 in pre- and post-docetaxel advanced prostate cancer: long-term follow-up of the Phase 1-2 study,” is currently available on the ASCO website at www.ASCO.org.

Phase 1-2 Trial Design
All patients in the open-label, dose-escalation, Phase 1-2 clinical trial had progressive disease upon enrollment and were heavily pretreated, with 77 percent having failed at least two lines of prior hormonal therapy and 54 percent having failed one or more chemotherapy regimens. A total of 140 men were enrolled in the trial, which evaluated MDV3100 doses between 30 and 600 mg/day. Patients could remain on treatment for as long as they continued to tolerate the drug and their disease did not progress. Efficacy endpoints included CTC counts, serum PSA levels, and soft tissue and bony metastases.

MDV3100 Phase 3 Clinical Development Program
MDV3100 is currently being evaluated in two global Phase 3 studies in patients with advanced prostate cancer.

The randomized, double-blind, placebo-controlled Phase 3 AFFIRM trial completed enrollment in November 2010. This trial of 1,199 patients with advanced prostate cancer who were previously treated with chemotherapy is evaluating 160 mg/day of MDV3100 versus placebo. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, safety and tolerability.

A second Phase 3 clinical trial of MDV3100 in advanced prostate cancer, the PREVAIL trial, is currently enrolling patients. This randomized, double-blind, placebo-controlled, multi-national trial of approximately 1,700 patients with advanced prostate cancer is evaluating MDV3100 at a dose of 160 mg taken orally once daily plus standard of care versus placebo plus standard of care. The co-primary endpoints of the trial are overall survival and progression-free survival; secondary endpoints include time to first skeletal-related event and time to initiation of cytotoxic chemotherapy. Information about patient eligibility and enrollment can be obtained by calling the PREVAIL study hotline toll-free at 1-888-243-4363.

About the Medivation/Astellas Collaboration
In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialize MDV3100. The companies are collaborating on a comprehensive development program that includes studies to develop MDV3100 for both early-stage and advanced prostate cancer. Subject to receipt of regulatory approval, the companies will jointly commercialize MDV3100 in the U.S. and Astellas will have responsibility for commercializing MDV3100 outside the U.S. Medivation received a $110 million up-front payment upon entering into the collaboration agreement, and is eligible to receive up to $335 million in development milestone payments, up to $320 million in commercial milestone payments, 50% of profits on sales in the U.S., and tiered, double-digit royalties on sales outside the U.S.

About MDV3100
MDV3100 is an investigational therapy in clinical development for advanced prostate cancer. In preclinical experiments published in Science in April 20093, the novel, triple-acting, oral androgen receptor antagonist provided more compIete suppression of the androgen receptor pathway than bicalutamide, the most commonly used anti-androgen. MDV3100 slows growth and induces cell death in bicalutamide-resistant cancers via three complementary actions – MDV3100 blocks testosterone binding to the androgen receptor, impedes movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation) and inhibits binding to DNA. In the preclinical experiments published in Science, MDV3100 was superior to bicalutamide in each of these three actions.

About Prostate Cancer
Prostate cancer is the second most common non-skin cancer among men in the world and it is the sixth leading cause of cancer death among men worldwide. Patients whose prostate tumors have stopped responding to, or are growing despite the use of, active hormone treatment strategies are considered to have advanced prostate cancer. These patients have a poor prognosis and few treatment options.

About Medivation
Medivation, Inc. is a biopharmaceutical company focused on the rapid development of novel small molecule drugs to treat serious diseases for which there are limited treatment options. Medivation aims to transform the treatment of these diseases and offer hope to critically ill patients and their caregivers. Together with its corporate partners Astellas and Pfizer, Medivation currently has investigational drugs in Phase 3 development to treat advanced prostate cancer, mild-to-moderate Alzheimer’s disease and Huntington disease. For more information, please visit us at www.medivation.com.

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Alzheimer’s patients, brain injury patients, and dementia sufferers may benefit from a newly discovered pill that grows brain cells. The drug, currently labeled P7C3 while it undergoes continued study, appears to provide a safe and effective option that helps support developing brain cells to become viable. Testing done on rats demonstrated that the older rats who had been dosed with P7C3 were capable of learning their way

through a maze when other rats, who had not received the drug, could not. The researchers hope the drug can be used to increase the effectiveness of Alzheimer’s drugs like Dimebon, which recently failed in clinical trials.

“For the sake of patients suffering from Alzheimer’s disease, it is hoped that the apparently marginal clinical utility of Dimebon might be enhanced by improvements in both its potency and ceiling of proneurogenic, neuroprotective efficacy,” the researchers wrote. “If so, our work offers concrete assays for the development of improved versions of these neuroprotective drugs.”

More than 25 million people currently suffer from Alzheimer’s disease, which is a progressive disease that destroys the brain until autonomic functions cease and the sufferer dies. P7C3 represents a hopeful breakthrough in research that could lend itself to other areas of brain trauma treatment, including helping people with ALS (also known as Lou Gehrig’s disease).

Dr. Thomas Insel, director of the National Institute on Mental Health, said, “This striking demonstration of a treatment that stems age-related cognitive decline in living animals points the way to potential development of the first cures that will address the core illness process in Alzheimer’s disease.” The National Institute on Mental Health helped fund the study.

The rats that were treated with the drug had three times as many developing brain cells. Researchers have since used P7C3 to create a derivative drug called A20 that shows even more promise. When the derivative was combined with Dimebon and Sereno, two test-phase Alzheimer treatments, it caused new brain cell growth stimulation.

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Feb. 2 (Bloomberg) — 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.

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.”

Drug Failures

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.”

Stock Ratings

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 rose $1.88, or 5.6 percent, to $35.70 at 4 p.m. in Nasdaq Stock Market composite trading. The shares have gained 80 percent in the last 12 months before today as investors anticipate the study results. Pfizer shares rose 45 cents, or 2.4 percent, to $19.24, and have climbed 29 percent in the past 12 months 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.

‘Very Excited’

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.

Russian Researchers

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.

Approved Drugs

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.

Losing Lipitor

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.

Additional Research

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.”

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.

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The cholinteresterase inhibitors thus far available  are currently only approved by the F.D.A. (The US Food and Drug Administration)  , are approved by the FDA as only being effective for Alzherimer patients who have thus far mild to moderate disease.  However these drugs and medications – that is the cholinesterase classification medication grouping, may well show promise for those who are in the earliest as well as later stages of the disease , as well.  In addition they could well be of benefit and benefits to those with mil cognitive impairment as well.

One large study evaluated the use of Aricept (dozepezil) in the treatment of mild cognitive  impairment and found that it significantly reduced conversion to active Alzheimer’s progressive disease.

Current Treatment for Alzheimer’s Disease – Prescription cholinesterase inhibitors include Exelon and Aricept. These drugs have varying side effects and can have contraindications with other medication, so it can be difficult for doctors to find the right pharmaceutical match and …

Methods and compositions using cholinesterase inhibitors – The invention provides methods for treating and/or preventing Alzheimer’s disease, psychiatric illnesses, encephalitis, meningitis, fetal alcohol syndrome, Karsakoff’s syndrome, anoxic brain injury, cardiopulmonary resuscitation …

alzheimer disease – These drugs are called cholinesterase inhibitors because they inhibit the enzymes that break down acetylcholine (acetylcholinesterase and butyrylcholinesterase). Some drugs target only acetylcholinesterase, whereas some target both …

Galantamine: Welsh daffodils containing galantamine may help fight … – Galantamine is a competitive and reversible cholinesterase inhibitor. It is believed it works by enhancing cholinergic function by increasing the concentration of acetylcholine in the brain. The atomics resolution 3D structure of the …

Cholinesterase Inhibitors Reduce Aggression, Wandering And … – Cholinesterase Inhibitors Reduce Aggression, Wandering And Paranoia In Alzheimer’s Disease.

While cholinesterase inhibitors are now believed to he most helpful in persons with severe Alzheimer’s disease ,sometimes patients can be maintained on these classes and classifications of drugs indefinitely due to the fact and observation that in clinical practice , that often patients who stop taking these drugs or types of medications deteriorate rapidly when the drugs are arbitrarily stopped or withdrawn.  Indeed there is new and upcoming evidence from studies that suggest that stopping cholinesterase inhibitors will result in decline in functioning to a level that the patient would have been at it they – he or she – had not been taking the drug in the first place.

In addition drugs in this class appear to have an added benefit in improving behaviour as well as overall cognitive abilities.

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