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