Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), announced the publication in Fertility and Sterility of data from a Phase 3 clinical study that showed that the investigational compound bazedoxifene/conjugated estrogens (BZA/CE) significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy when compared to placebo. In this study, uterine bleeding was not statistically different from placebo and the rate of endometrial hyperplasia in doses being considered for therapeutic use was <1%. BZA/CE is being studied by Wyeth Pharmaceuticals for the treatment of moderate-to-severe menopausal vasomotor symptoms such as hot flushes, night sweats and vulvar and vaginal atrophy, and for the prevention of postmenopausal osteoporosis.

The data, published online July 27, 2009 in the peer-reviewed journal Fertility and Sterility, is from the Selective estrogens Menopause And Response to Therapy (SMART-1) clinical trial. SMART-1 was designed to explore the hypothesis that bazedoxifene, when paired with conjugated estrogens, may have the potential to eliminate the need for progestin in menopausal therapy in women with an intact uterus. BZA/CE is characterized by Wyeth as a TSEC (tissue selective estrogen complex) as it combines a selective estrogen receptor modulator (SERM) with conjugated estrogens.

Across the SMART-1 trial, the incidence of treatment-emergent adverse events, breast pain, serious adverse events and withdrawals due to adverse events were similar among the active treatment groups and placebo.

About SMART-1

SMART-1 was a two-year, multinational, multicenter, randomized, double-blind, placebo- and active-controlled Phase 3 study that evaluated 3,397 healthy, postmenopausal women with an intact uterus aged 40 to 75 years. The primary end point of the SMART-1 trial was incidence of endometrial hyperplasia at one year. Secondary end points included bone mineral density (BMD) at two years, menopausal vasomotor symptoms at four and 12 weeks, vaginal maturation index at six months, menopause-related quality of life measures, and overall safety and tolerability.

Titles and Summary of Findings From Published Manuscripts

1. Endometrial Protection in Menopausal Therapy with a Tissue Selective Estrogen Complex (TSEC) Containing Bazedoxifene/Conjugated Estrogens (Pickar JH, et al)

To evaluate endometrial effects, biopsies were performed at screening and at months six, 12, and 24, or when subjects withdrew from the study and more than three months had elapsed since their last assessment. Treatment with BZA/CE doses being considered for therapeutic use were associated with rates of endometrial hyperplasia <1%. These rates were not significantly different from those reported with placebo over two years of study.

2. Bazedoxifene/Conjugated Estrogens (BZA/CE): Incidence of Uterine Bleeding in Postmenopausal Women (Archer DF, et al)

To evaluate the effect of treatment with BZA/CE on uterine bleeding, trial participants were asked to record in a diary whether or not they experienced bleeding and/or spotting. The mean number of bleeding or spotting days with BZA/CE was not statistically different from placebo over two years of therapy.

3. Evaluation of Bazedoxifene/Conjugated Estrogens (BZA/CE) for the Treatment of Menopausal Symptoms and Effects on Metabolic Parameters and Overall Safety Profile (Lobo R, et al)

Results from a sub-analysis suggest that treatment with BZA/CE significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy compared with placebo. In this study, analysis of most clinical laboratory determinations revealed no clinically important differences among treatment groups and no trends of concern. The incidences of breast pain and adverse events were similar between BZA/CE and placebo.

4. Efficacy of Tissue-Selective Estrogen Complex (TSEC) of Bazedoxifene/Conjugated Estrogens (BZA/CE) for Osteoporosis Prevention in At-Risk Postmenopausal Women (Lindsay R, et al)

When compared with placebo, treatment with BZA/CE increased BMD at the lumbar spine and total hip at 24 months. These results suggest that women in the BZA/CE groups gained bone mass while women in the placebo treatment group lost BMD.

About Menopause

Approximately 40 million women in the United States are of menopausal age (45 to 64 years). Of these women, 17 million experience vasomotor symptoms; 9 million experience moderate to severe symptoms. Menopause is different for every woman, and vasomotor symptoms can last from a few months to many years and they can be mild, moderate or severe enough to interfere with daily life. The majority of menopausal women experiencing moderate to severe vasomotor symptoms are not currently treating their symptoms.

About Fertility and Sterility

Fertility and Sterility is the official publication of the American Society of Reproductive Medicine, which publishes peer-reviewed original articles of research relevant to reproductive endocrinology, physiology, immunology, genetics and menopause.

About Wyeth Pharmaceuticals

Wyeth Pharmaceuticals has leading products in the areas of women’s health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products.

Wyeth is one of the world’s largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products, nutritionals and non-prescription medicines that improve the quality of life for people worldwide. The Company’s major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.

The statements in this press release that are not historical facts are forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. In particular, clinical trial data are subject to differing interpretations, and the views of regulatory agencies, medical and scientific experts and others may differ from ours or those expressed in the referenced publication. The Phase 3 clinical trial data presented and published to date reflect only a portion of the totality of data available from Phase 3 studies of BZA/CE and, accordingly, do not represent the totality of data and other information that may affect regulatory review and commercialization of BZA/CE. There can be no assurance that BZA/CE will ever receive regulatory approval or be successfully developed and commercialized. Other risks and uncertainties include, among others, risks related to our proposed merger with Pfizer, including satisfaction of the conditions of the proposed merger on the proposed timeframe or at all, contractual restrictions on the conduct of our business included in the merger agreement, and the potential for loss of key personnel, disruption in key business activities or any impact on our relationships with third parties as a result of the announcement of the proposed merger; the inherent uncertainty of the timing and success of, and expense associated with, research, development, regulatory approval and commercialization of our products and pipeline products; government cost-containment initiatives; restrictions on third-party payments for our products; substantial competition in our industry, including from branded and generic products; emerging data on our products and pipeline products; the importance of strong performance from our principal products and our anticipated new product introductions; the highly regulated nature of our business; product liability, intellectual property and other litigation risks and environmental liabilities; the outcome of government investigations; uncertainty regarding our intellectual property rights and those of others; difficulties associated with, and regulatory compliance with respect to, manufacturing of our products; risks associated with our strategic relationships; global economic conditions; interest and currency exchange rate fluctuations and volatility in the credit and financial markets; changes in generally accepted accounting principles; trade buying patterns; the impact of legislation and regulatory compliance; risks and uncertainties associated with global operations and sales; and other risks and uncertainties, including those detailed from time to time in our periodic reports filed with the Securities and Exchange Commission, including our current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption “Item 1A, Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2008, which was filed with the Securities and Exchange Commission on February 27, 2009. The forward-looking statements in this press release are qualified by these risk factors. We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

Source: Wyeth

WASHINGTON, July 29 — Dental fillings that contain mercury are safe, but have been upgraded from low-risk to moderate-risk devices, the FDA said.

In its final rule on dental amalgam, the FDA recommended that product labeling include warnings against use in patients with mercury allergy and that dental professionals use adequate ventilation when handling the product.

The label should also have a statement about the product’s benefits and risks — including those from inhaling mercury vapor, the agency said.

The FDA’s action is the latest development in a long and contentious battle involving the agency, the American dental establishment, and a variety of consumer and environmental groups who argue that mercury-based amalgam fillings are potentially harmful.

The rule was originally proposed in 2002 but received a large number of comments and was investigated further.

A 2006 advisory committee meeting of dental and neurology experts asked that the FDA probe deeper into the scientific literature on dental amalgam before making a final rule. Consumer groups eventually filed a lawsuit to compel the agency to act.

Throughout its review, the agency said it considered 200 scientific studies, reflected in the final rule issued today.

The consumer groups who originally sued the agency expressed anger at the ruling, saying the agency reneged on promises to require tougher warnings about mercury-based amalgam, particularly involving children and pregnant women.

“FDA broke its contract and broke its word that it would put warnings for children and unborn children,” Charles Brown of Consumers for Dental Choice, told the Associated Press. He pledged to go back to court.

Dental amalgam is 50% liquid elemental mercury and 50% powdered metals including silver, tin, and copper.

The FDA considers dental amalgam fillings safe for adults and children age 6 and up. The agency says the amount of mercury in patients with dental amalgam fillings is well below levels associated with adverse health effects.

Dental amalgam is a “pre-amendment device,” meaning it was in use prior to May 28, 1976, when the FDA was given broad authority to regulate medical devices.

That law required the FDA to issue regulations classifying pre-amendment devices according to their risk into class I, II, or III.

Amalgam fillings are now Class II devices. Most fillings today are made of a composite of material that matches the color of tooth enamel, but many dentists say that for some applications, amalgam is still the material of choice.

The agency had previously classified the two separate parts of amalgam but had not issued a separate regulation classifying the combination of the two.

WHEELING, W.Va., July 29 — Workers at a major U.S. generic drug manufacturing facility regularly violated quality control protocols until executives discovered the practice this spring, a local newspaper reported.

So-called “red screens” on computers monitoring production at the Mylan Laboratories plant in Morgantown, W.Va., were routinely deleted or overridden, according to the Pittsburgh Post-Gazette, citing an internal company report.

Company policy calls for production to be halted while the cause for a red screen is investigated and corrected. Circumventing the computer alerts created the potential for drugs to be produced with incorrect amounts of the active ingredients or other problems.

Mylan issued a statement yesterday saying that FDA inspectors visited the plant Monday, after the company informed the agency of the newspaper article.

According to the company, the agency found no evidence of data deletion and gave Mylan a clean bill of health.

Some 19 billion doses of many popular generic drugs are produced annually at the Morgantown plant.

After the Post-Gazette story ran on June 26, Mylan issued a statement denying that any improperly produced drugs left the plant, although it did not question the leaked report’s authenticity.

“This issue had no impact on the quality of our product,” the statement said. “Our investigation of the issue demonstrates that our quality systems are working, not the contrary.”

Referring to the FDA visit on Monday, the company said, “All data was reviewed and was present and accounted for; the agency agreed that this was a minor Standard Operating Procedures deviation that existed, was fully investigated, and all corrective actions were fully implemented by Mylan.”

The statement also decried what it called “baseless” and “unfounded” accusations in the newspaper report, referring to comments from former FDA inspectors and consultants who said the company’s procedures appeared to be lax.

According to the leaked report, which summarized an internal investigation, workers had found ways to prevent red screens from coming to the attention of quality control managers.

Company executives caught wind of the practices on May 11 and launched the probe. They also immediately stopped all production at the facility and called employees into a meeting where the importance of following quality-control protocols scrupulously was emphasized, the newspaper said.

An anonymous tipster claimed that managers had distributed passwords to production workers that would allow red screens to be cleared, and some workers said that supervisors knew about and even encouraged the practices.

But most workers claimed they couldn’t remember who showed them how to get around the red screens.

Some said the red screens were frequently false alarms, resulting from malfunctioning sensors rather than actual problems with drug production.

The report did not indicate how many red screens were deleted or how often, although it quoted one worker as saying five or six were cleared in a single shift.

According to the report, workers said they felt pressured to maximize production at the Morgantown plant in order to keep the company from moving some of its manufacturing to a facility in India.

However, that plant is facing quality accusations too. A recent inspection by the World Health Organization, which had arranged for generic HIV medications to be produced there, revealed “major deviations” from good manufacturing practices.

Other generic manufacturers in the U.S. have also been hit with quality control problems.

Late last month, for example, Caraco Pharmaceutical Laboratories was ordered by the FDA to halt shipments from three plants, with federal marshals sent to enforce the order. (See FDA Stops Shipments of 33 Generic Drugs from Caraco Plants)

Related sources:

• From the Pittsburgh Post-Gazette
• Mylan statement on FDA inspection

Related Article(s):

• FDA Stops Shipments of 33 Generic Drugs from Caraco Plants

A small trial testing the benefits in multiple sclerosis (MS) of a drug used to treat type II diabetes, in combination with beta-interferon-1a, has been shown to potentially prevent brain cell loss.

The results of the trial in 21 people investigating the effects of pioglitazone (also known as net/108/1/Actos/”>Actos) were published last month in the Journal of Neuroimmunology.

Although the results of the trial showed some evidence of less damage in the brains of people with MS, there were too few people in the study to determine whether this effect was real.

Dr. Susan Kohlhaas, Research Communications Officer at the MS Society said, “These results suggest that pioglitazone may have some benefit in combination with beta-interferon for people with relapsing remitting MS, but this trial is not large enough to determine exactly what that benefit will be.

She added, “A larger clinical trial is needed to decide whether or not pioglitazone will be of benefit to people with MS.”

Source
Multiple Sclerosis Society

View drug information on ACTOS.

Walter and Eliza Hall Institute scientists have created a weakened strain of the malaria parasite that will be used as a live vaccine against the disease. The vaccine, developed in collaboration with researchers from the US, Japan and Canada, will be trialled in humans from early next year.

Malaria kills more than one million people each year and destroys - through premature death and disability - the equivalent of at least 35 million years of healthy, productive human life every year.

Professor Alan Cowman, head of the institute’s Infection and Immunity division, said in developing the vaccine the research team had deleted two key genes in the Plasmodium falciparum parasite - which causes the form of malaria most deadly to humans. By removing the genes the malaria parasite is halted during its liver infection phase, preventing it from spreading to the blood stream where it can cause severe disease and death.

Their success in genetically modifying the parasite and thereby preventing its invasion of red blood cells is published in the current issue of the Proceedings of the National Academy of Sciences USA.

Professor Cowman said similar vaccines had been tested in mice and offered 100 per cent protection against malaria infection. He said it was hoped the vaccine would produce similar results in humans. “Although two genes have been deleted the parasite is still alive and able to stimulate the body’s protective immune system to recognize and destroy incoming mosquito-transmitted deadly parasites,” Professor Cowman said.

This approach to vaccine development - using a weakened form of the whole organism that causes a particular disease - has proven successful in eradicating smallpox and controlling diseases such as flu and polio.

Professor Cowman said the research team, which includes Dr Matthew O’Neill and Dr Alex Maier from the institute as well as scientists from the Seattle Biomedical Research Institute, the Walter Reed Army Institute for Research and the University of Maryland, had used knowledge from several decades ago - when scientists proved that irradiated malaria parasites provide protection against subsequent malaria infection in animal models and humans - in developing the vaccine.

“Although vaccines are under development that use whole malaria parasites weakened by irradiation to protect against infection, their safety and effectiveness rely on a precise irradiation dose and trial results have been variable,” Professor Cowman said. “We believe that our genetically attenuated parasite approach provides a safe and reproducible way of developing a whole organism malaria vaccine.”

Professor Cowman said it was unlikely the weakened parasites used in the vaccine would regain their potency as the genes had been deleted from the genome and could not be recreated by the parasite. “In addition, the ‘one-two punch’ approach of deleting two essential genes make it extremely unlikely that the attenuated parasite vaccine could restore its capacity to multiply and lead to disease,” he said.

The human trials of the vaccine will take place at the Walter Reed Army Institute of Research in Maryland, US. The genetically attenuated parasites to be used in the trial are being manufactured at the Walter and Eliza Hall Institute, which has the only facility worldwide capable of producing genetically-altered malaria parasites that comply with the good manufacturing practice guidelines required for human clinical trials.

The research is supported by a US$17 million, five-year grant from the Bill & Melinda Gates Foundation.

Source:
Ms Penny Fannin

Walter and Eliza Hall Institute

Researchers at the Peninsula Medical School have received a grant of over £39,000 from the charity Deafness Research UK, to investigate the role of brain tumours causing deafness in children and adults and the development of therapies using in vitro models.

These tumours and a variety of other tumours are caused by mutations affecting a protein called merlin, which in turn cause cancers in a range of cell types including Schwann cells in the nervous system. Schwann cells produce the sheaths that surround and insulate neurons.

Although the tumours are benign, they are frequent. They can be inherited and come in numbers. The sheer number of them can overwhelm a patient, often leading to deafness and eventually to death. Patients can suffer from 20 to 30 tumours at any one time, and the condition typically affects older children and young adults.

No therapy, other than invasive surgery aiming at a single tumour and which may not eradicate the full extent of the tumours, exists. The hereditary condition affects one in every 2,500 people worldwide. It can affect any family, regardless of past history, through gene mutation and currently there is no cure.

In some cases, pressure from the tumours affect the process of hearing leading to hearing loss or total deafness. The research will use a human acoustic neuroma in vitro model to identify how and why the tumours grow and eventually lead to hearing damage, and to test drug-based therapies designed to alleviate the problem.

The research is led by Professor Oliver Hanemann, Chair of Clinical Neurobiology at the Peninsula Medical School. He said: “We have already achieved some success in re-profiling an existing drug called sorafenib by using the human in-cell model. The re-profiled drug has a positive affect on multiple brain tumours. As a consequence, we can go straight to clinical trials and introduce therapies to patients sooner rather than later using sorafenib or similar drugs..”

Vivienne Michael, Chief Executive of Deafness Research UK, said: “This is clearly an important research project that could significantly improve the treatment available for those with acoustic neuroma and the charity is delighted to be funding it. Acoustic neuroma is worrying enough in its own right; when multiple tumours occur they need treating and traditional cancer therapies are not an option. Currently, treatment involves surgical removal of the tumours but this leads to damage of the auditory nerve and can cause total deafness with potentially devastating effects on the lives of those involved.

“Great progress has been made in identifying target molecules for treatment, and this research will go a long way towards establishing the best potential drug for non-invasive therapy. Ultimately this would avoid the need for surgery and mean that people who currently face deafness as a result of acoustic neuroma would retain their hearing.”

Deafness Research UK is the only organisation totally dedicated to medical research of this type - researching treatments and cures for deafness, tinnitus, and other deafness-related conditions.

Source:
Andrew Gould

The Peninsula College of Medicine and Dentistry

Can-Fite BioPharma (TASE:CFBI), a biotechnology company traded on the Tel Aviv Stock Exchange announced that, following the approval by the Israel Ministry of Health and Rabin MC Ethics Committee, a phase I/II clinical trial with CF102 for the treatment of HCV will now start enrolling patients.

The trial will investigate the safety and efficacy of CF102 in patients with HCV. This ascending-dose trial will be conducted at the Rabin Medical Center and include 32 patients.

HCV is predominantly transmitted through body fluids and less frequently by sexual intercourse, and no vaccines are currently available. About 50% to 85% of HCV infected patients develop a chronic form of the disease, of whom 25% to 76% develop active chronic disease and cirrhosis, which is the leading cause of liver transplantation in Europe and the US and greatly increases the risk of liver cancer. Patients are currently offered drug therapy that generally consists of oral Ribavirin in combination with interferon injections. These drugs have severe adverse events and most patients rapidly become refractory to them. The market size today is more than 3 Billion $ and is estimated to grow to around 8.3 Billion $ on 2012.

The Company previously reported that preclinical studies have suggested that the drug is active against HCV via inhibition of NS5, RNA dependent RNA polymerase. CF102 was also found to trigger programmed cell death (apoptosis) of liver cancer cells. The Company recently announced the successful completion of a Phase I clinical study with CF102 under an IND in the US, showing a safety profile and a linear pharmacokinetic behavior of the drug.

Prof. Pnina Fishman, CEO of Can-Fite, said that “the initiation of the Phase I/II trial in HCV demonstrates the progress of the company in its clinical development program. Based on the definitive molecular mechanism of CF102 which targets the highly specific enzyme NS5 in the viral replication cycle, we have a great belief in the performance of the drug.”

In keeping with its financial reports, Can-Fite expects to release within weeks the results of a phase II clinical trial with CF101 for the treatment of Psoriasis. The company concluded successfully a Phase II study in Dry Eye Syndrome.

Source
Can-Fite BioPharma

Medtronic, Inc. (NYSE: MDT) announced completion of a 12-month follow up in the STOP-AF (Sustained Treatment of Paroxysmal Atrial Fibrillation) clinical trial evaluating the first cryoballoon catheter technology designed to treat paroxysmal atrial fibrillation - the Medtronic Arctic Front® CryoAblation Catheter System. Atrial fibrillation (AF) is the most common arrhythmia affecting more than 3 million Americans and 7 million people worldwide.1 After the study data are analyzed and filed with regulatory authorities, the results will be shared at an upcoming medical meeting. The system is approved for use in Europe, Australia and Hong Kong and is under investigational use in the United States.

The Arctic Front system uses cryoablation, or freezing, to ablate heart tissue between the pulmonary veins and the left atrium. The goal of an ablation is to stop the arrhythmia at the source. During cryoablation, a coolant is released into the catheter’s balloon causing the balloon to freeze and ablate the heart tissue. Freezing helps the balloon maintain contact with the tissue being ablated.

“This catheter is designed to allow physicians to more efficiently and easily ablate than with a single tip ablation procedure,” said Kevin Wheelan, M.D., chief of staff at Baylor Heart and Vascular in Dallas and investigator in the STOP-AF trial. “In this trial, the cryoballoon’s stability simplified the process for these types of cardiac ablation procedures.”

“Arctic Front is one of the tools in Medtronic’s growing AF Solutions portfolio,” said Reggie Groves, vice president and general manager of Medtronic’s AF Solutions division. “Our goal is to develop and deliver breakthrough therapies that help physicians to effectively treat AF patients faster, safer, easier, and with more predictable procedure times.”

Medtronic recently acquired CryoCath LP and Ablation Frontiers, LLC, which along with its existing EP Systems diagnostic and RF ablation catheters, collectively form Medtronic’s AF Solutions division.

About the Medtronic Arctic Front CryoAblation Catheter System

The Medtronic Arctic Front CryoAblation Catheter System technologies used in the STOP-AF trial include:

- The Arctic Front cryoballoon catheter, which inflates and fills with coolant to ablate between the pulmonary veins and the left atrium;
- The FlexCath® Steerable Sheath, which helps deliver and position the cryocatheter in the left atrium;
- The Freezor® MAX Cardiac CryoAblation Catheter, which is a single-point catheter used to provide additional ablations; and
- The CryoConsole, which houses the coolant, electrical and mechanical components that run the catheter during a cryotherapy procedure.

About STOP-AF

This pivotal trial is studying the safety and efficacy of the Medtronic Arctic Front CryoAblation Catheter System in paroxysmal AF patients as compared to drug therapy. Patients were randomized to receive ablation therapy or commonly used drug treatments. For every three patients enrolled, approximately two received an ablation and one was randomly assigned to the drug therapy group. Twenty-five U.S. and Canadian centers enrolled 245 patients who were followed for at least 12 months after the ablation procedure. Results will be submitted in consideration for U.S. Food and Drug Administration (FDA) approval for the Medtronic Arctic Front CryoAblation Catheter System.

About Atrial Fibrillation

Atrial fibrillation an irregular quivering or rapid heart rhythm in the upper chambers (atria) of the heart. Paroxysmal AF occurs when the irregular rhythm starts and stops suddenly on its own. Untreated AF patients have a two to seven times higher risk of stroke.2 Atrial fibrillation causes inefficient pumping of the heart and can lead to other rhythm problems as well as chronic fatigue and heart failure.

Source
Medtronic

Pfizer Inc announced today results from two Phase 1 safety studies, one of PF-04360365, a humanized anti-amyloid monoclonal antibody (mAb), and another of dimebon (latrepirdine*) in combination with donepezil HCl tablets, in patients with Alzheimer’s disease.1,2 Based on the Phase 1 study results, PF-04360365 has advanced into Phase 2.3 Dimebon (latrepirdine), being co-developed by Pfizer and Medivation Inc., is in Phase 3 development.4 These data were presented this week at the Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease (ICAD) in Vienna, Austria.

A Phase 1, single-dose, dose escalation study (0.1 to 10 mg/kg) showed that the investigational compound PF-04360365 was well-tolerated in all patients, with no clinical or imaging evidence of vasogenic edema, and no new microhemorrhage or encephalitis reported to date in the ongoing follow-up period.1 In the Phase 1 dimebon (latrepirdine) study, results from a four-week, placebo-controlled trial of 24 patients on a stable dose of donepezil for at least 60 days showed that dimebon (latrepirdine) was well-tolerated when used in combination with donepezil.2 Alzheimer’s disease, a progressive and degenerative brain disease, is the most common type of dementia.5 Worldwide societal costs associated with dementia were estimated to be $315.4 billion in 2005.6

“Alzheimer’s disease is a destructive illness and Pfizer is committed to lifting the burden of the disease on patients and those who care for them,” said Steven J. Romano, MD, vice president, Medical Affairs Head for Pfizer’s Primary Care Business Unit. “We are continuing to work with the global Alzheimer’s community to advance research in Alzheimer’s disease and currently have an investigational compound, dimebon (latrepirdine), in Phase 3 and two other compounds in Phase 2.”

Pfizer’s mAb PF-04360365 Well-Tolerated in Phase 1

Pfizer’s PF-04360365 is a highly selective and potent monoclonal antibody that targets the C-terminal end of the beta amyloid 1-40 peptide. It does not bind to the Amyloid Precursor Protein (APP), from which beta amyloid is derived, and which the body needs to function normally. This may contribute to a favorable risk/benefit profile, which will be further examined in long-term pivotal trials. This mAb has been designed to remove the toxic beta amyloid from the brain and potentially slow or halt Alzheimer’s disease progression.

In the Phase 1 double-blind, placebo controlled trial, patients with mild-to-moderate Alzheimer’s disease (n=37) were randomized to one of five study groups to receive PF-04360365 as a single two-hour intravenous infusion ranging from 0.1-10 mg/kg (n=26) or placebo (n=11).1 These patients were monitored for one-year, and to date, four of the five study groups have completed the one year observation period. Results showed PF-04360365 was well-tolerated over this dose range. Routine safety lab values were unremarkable and there were no safety signals from brain Magnetic Resonance Imaging (MRIs), electrocardiograms (ECGs), cognitive scales or physical/neurological examinations.1 While the one-year observation period is still ongoing, the most common adverse events observed to date were upper respiratory tract infection (n=10), headache (n=9), back pain (n=6) and diarrhea (n=5), and all were mild to moderate in severity.1

“We are encouraged by these preliminary safety results and look forward to studying the safety, as well as the efficacy, of PF-04360365 in Phase 2 multiple dose trials,” said Martin M. Bednar, MD, PhD, senior director and Pfizer clinical lead for the PF-04360365 program. “As we explore multiple compounds and mechanisms to treat Alzheimer’s disease, safety is of paramount importance given the vulnerability of the elderly population afflicted.”

Dimebon (latrepirdine) Shown to be Well-Tolerated in a Four-Week Combination Study

In another study presented earlier in the week, Medivation and Pfizer announced that the investigational drug dimebon (latrepirdine) was well-tolerated when used in combination with donepezil HCl tablets. In this Phase 1, four-week, placebo-controlled safety study, 24 patients with Alzheimer’s disease on a stable dose of donepezil for at least 60 days were randomized to receive dimebon (latrepirdine) or placebo for two to four weeks.2

The first group of patients enrolled (dimebon, n=9, placebo, n=5) underwent gradual dose-titration in one-week intervals ranging from 2.5 mg three times daily (TID) up to 20 mg TID, over one month. The second group of patients (dimebon, n=6, placebo, n=4) titrated from 10 mg TID for one week to 20 mg TID for one week. No serious adverse events were reported in the study.2 The most commonly reported adverse events compared to placebo were fatigue (dimebon, n=3/15, placebo, n=0), abdominal distension (dimebon, n=2/15, placebo, n=0), fall (dimebon, n=2/15, placebo, n=0), hyperkalemia (dimebon, n=2/15, placebo, n=1/9) and nightmare (dimebon, n=2/15, placebo, n=0). These events were mild to moderate in severity and resolved with continued treatment.2

In addition to PF-04360365 and dimebon (latrepirdine), Pfizer is investigating several other compounds targeting different pathways for the treatment of Alzheimer’s disease.

About Dimebon (latrepirdine)

Dimebon (latrepirdine) is an investigational compound for the treatment of Alzheimer’s disease. Three Phase 3 trials are underway and two additional Phase 3 trials are scheduled to start later this year. CONCERT is a 12-month clinical trial examining the safety and efficacy of dimebon (latrepirdine) when added to donepezil in patients with mild to moderate Alzheimer’s disease, which recently began enrollment. CONCERT is designed to complement previous and ongoing studies evaluating the potential for dimebon (latrepirdine) to be used as monotherapy, as well as in combination with donepezil.

Based on preclinical studies completed thus far, dimebon (latrepirdine) is thought to potentially stabilize or improve mitochondrial function in a way that prevents neurons from damage and dysfunction. The mechanism of action of dimebon (latrepirdine) is thought to be distinct from currently available Alzheimer’s medications.

* Latrepirdine is the proposed generic (nonproprietary) name for dimebon.

About Pfizer’s Commitment to Alzheimer’s Disease

Alzheimer’s disease touches everyone. As the world population over age 65 grows rapidly, more people are at risk for this degenerative brain disease. Pfizer researchers are working diligently to find a way to help those affected by the disease. Building on a foundation of more than two decades of research, education and support for the global Alzheimer’s community, the company is investing heavily to advance understanding of the disease. Pfizer forms partnerships to develop novel therapies, supports policy initiatives that help ensure availability and access to treatments, and works collaboratively with academia and government on biomarker and diagnostic research initiatives to enable earlier Alzheimer’s diagnosis.

Pfizer is studying different compounds targeting various central nervous system pathways that may be able to better treat Alzheimer’s disease symptoms and/or modify its underlying causes. Four novel compounds in clinical trials include: dimebon (latrepirdine), an investigational compound believed to impact mitochondrial function currently in Phase 3 trials; an antagonist of the Receptor for Advanced Glycation End-products (RAGE) in Phase 2 trials in partnership with the Alzheimer’s Disease Cooperative Study (ADCS) group; a highly selective humanized anti-amyloid monoclonal antibody in Phase 2 trials; and a phosphodiesterase-9A (PDE9A) inhibitor, moving into Phase 2 trials. Pfizer is co-developing dimebon (latrepirdine) with Medivation, and the RAGE development program is a Pfizer-TransTech collaboration.

References

1. ICAD Submitted Abstract #O4-04-03. Safety and pharmacokinetics of the anti-amyloid monoclonal PF-04360365 following a single infusion in patients with mild-to-moderate Alzheimer’s disease: Preliminary results. Oral presentation. July 15, 2009: 3:30-3:45 p.m. M. Bednar - Presenter. 2009 International Conference on Alzheimer’s Disease (ICAD), Vienna, Austria. July 11-16, 2009.

2. ICAD Submitted Abstract #P1-254. A safety, tolerability and pharmacokinetic study of dimebon in patients with Alzheimer’s disease already receiving donepezil. Poster Session. July 12, 2009: 12:30-3:00 p.m. P Tariot - Presenter. 2009 International Conference on Alzheimer’s Disease (ICAD), Vienna, Austria. July 11-16, 2009.

3. ClinicalTrials.gov. Multiple IV Dose Study of PF-04360365 In Patients With Mild To Moderate Alzheimer’s Disease. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00722046. Accessed June 17, 2009.

4. ClinicalTrials.gov. Safety and Efficacy Study Evaluating Dimebon in Patients With Mild to Moderate Alzheimer’s Disease on Donepezil (CONCERT). Available at: http://www.clinicaltrials.gov/ct2/show/NCT00829374. Accessed June 17, 2009.

5 Alzheimer’s Association. What is Alzheimer’s? Accessed at: http://alz.org/alzheimers_disease_what_is_alzheimers.asp? Accessed June 9, 2009.

6. Wimo A, Winblad B, and Jonsson L. An estimate of the total worldwide societal costs of dementia in 2005. Alzheimer’s Dement. 2007;3:81-91.

Source
Pfizer Inc

U.S. House of Representative Democrats unveiled their bill for health care reform - the America’s Affordable Health Care Choice of 2009. In response, National Community Pharmacists Association (NCPA) Executive Vice President and CEO Bruce T. Roberts, RPh, issued the following statement:

“Community pharmacists play a critical role in the health care system. NCPA is committed to ensuring that any health reform legislation does two things: First, it should utilize medication therapy management and other pharmacist-delivered health care services to improve patient outcomes and reduce overall costs, such as from improper medication use. Second, and more importantly, Congress should assure that there is a viable community pharmacy infrastructure to deliver quality health care to millions of patients across America.

“This is a sweeping legislative proposal that requires additional, careful review. However, we are pleased that the bill begins to reform the system that will be used to pay pharmacies for generic medications dispensed to Medicaid patients. We need to work with the Congress and the states as this bill moves forward to assure that appropriate payment exists for pharmacists to dispense lower-cost generic medications. For Medicaid beneficiaries in underserved rural or urban areas, community pharmacies are often the sole health care provider.

“We also appreciate the inclusion of provisions that exempt community pharmacists who provide durable medical equipment, such as diabetes testing strips, from duplicative and onerous accreditation and surety bond requirements. This will allow for patients to continue accessing these valuable health care products.
“On these and other matters we will continue working with the House, Senate and White House to ensure that health care reform allows community pharmacies to remain a valuable are a valuable cog in America’s health system. When that occurs patients will have better outcomes and costs saving can be found.”

Source
National Community Pharmacists Association

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