Pfizer Announces Submission of Palbociclib New Drug Application to the FDA

Pfizer Inc. today announced it has completed the submission of a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for palbociclib. This NDA requests FDA approval of palbociclib, in combination with letrozole, for the treatment of postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease. The submission is based on the final results of PALOMA-1, a randomized, Phase 2 trial comparing palbociclib plus letrozole versus letrozole alone in this population of patients.

Pfizer Announces Submission of Palbociclib New Drug Application to the FDA

Palbociclib received Breakthrough Therapy designation from the FDA in April 2013, for the first-line systemic treatment of women with advanced or metastatic ER+, HER2- breast cancer. This designation was based on interim data from the PALOMA-1 trial.

FDA Grants Amgen Priority Review Designation For Ivabradine For The Treatment Of Chronic Heart Failure

Amgen announced the U.S. Food and Drug Administration (FDA) has granted priority review designation for ivabradine for the treatment of chronic heart failure (HF). Ivabradine is an oral drug that inhibits the I_f current ("funny" current) in the sinoatrial node, the body's cardiac pacemaker.  Ivabradine works to slow the heart rate without negative effects on myocardial contractility or ventricular repolarization.  Heart failure is a common condition that affects approximately 26 million worldwide, including approximately 5.1 million people in the U.S. 

FDA Grants Amgen Priority Review Designation For Ivabradine For The Treatment Of Chronic Heart Failure

FDA Approves Eliquis (apixaban) for the Treatment of Deep Vein Thrombosis and Pulmonary Embolism

In continuation of my update on Apixaban (BMS-562247-01, tradename Eliquis)

Bristol-Myers Squibb Company and Pfizer Inc.  announced the U.S. Food and Drug Administration (FDA) has approved a Supplemental New Drug Application (sNDA) for Eliquis for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. Combined, DVT and PE are known as VTE. It is estimated that every year, approximately 900,000 Americans are affected by DVT and PE.

FDA Approves Eliquis (apixaban) for the Treatment of Deep Vein Thrombosis and Pulmonary Embolism

Actavis Announces FDA Acceptance for Filing of NDA for Eluxadoline

Actavis plc (NYSE: ACT) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing Actavis' New Drug Application (NDA) for eluxadoline, an investigational drug for the treatment of diarrhea and abdominal pain in men and women with diarrhea predominant Irritable Bowel Syndrome (IBS-D). Actavis' NDA for eluxadoline has been granted priority review status by the FDA.

Actavis Announces FDA Acceptance for Filing of NDA for Eluxadoline

FDA Advisory Committee Votes 14-1 in Favor of Saxenda (liraglutide) for Obesity

In continuation of my update on Lirglutide

Novo Nordisk today announced that the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) of the Food and Drug Administration (FDA) has completed its meeting regarding the New Drug Application (NDA) for Saxenda, the intended brand name for liraglutide 3 mg, a once-daily human GLP-1 analogue for the treatment of obesity.

FDA Advisory Committee Votes 14-1 in Favor of Saxenda (liraglutide) for Obesity

New class of compounds protect brain cells from traumatic brain injury

A new class of compounds has now been shown to protect brain cells from the type of damage caused by blast-mediated traumatic brain injury (TBI). Mice that were treated with these compounds 24-36 hours after experiencing TBI from a blast injury were protected from the harmful effects of TBI, including problems with learning, memory, and movement.

Traumatic brain injury caused by blast injury has emerged as a common health problem among U.S. servicemen and women, with an estimated 10 to 20 percent of the more than 2 million U.S. soldiers deployed in Iraq or Afghanistan having experienced TBI. The condition is associated with many neurological complications, including cognitive and motor decline, as well as acquisition of psychiatric symptoms like anxiety and depression, and brain tissue abnormalities that resemble Alzheimer's disease.

"The lack of neuroprotective treatments for traumatic brain injury is a serious problem in our society," says Andrew Pieper, M.D., Ph.D., senior study author and associate professor of psychiatry, neurology, and radiation oncology at the University of Iowa Carver College of Medicine. "Everyone involved in this work is motivated to find a way to offer hope for patients, which today include both military personnel and civilians, by establishing a basis for a new treatment to combat the deleterious neuropsychiatric outcomes after blast injury."

It is known that TBI, as well as certain neurodegenerative diseases, damages axons - the tendril-like fibers that sprout from brains cells (neurons) and form the connections called synapses. In TBI, axon damage is followed by death of the neuron. The new study, published Sept. 11 in the journal Cell Reports, shows that a group of compounds, called the P7C3 series, blocks axon damage and preserves normal brain function following TBI.

Pieper led the team of scientists that discovered the P7C3 compound several years ago at UT Southwestern Medical Center. Subsequent studies showed that the root compound and its active analogs protect newborn neurons from cell death and also protect mature neurons in animal models of neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis (ALS).

The researchers have also previously shown efficacy of P7C3 molecules in brain injury due to concussion, and plan to investigate whether these compound might be applicable in stroke as well, given that there appear to be common factors mediating neuronal cell death in these conditions.
Ref : http://www.cell.com/cell/abstract/S0092-8674(10)00672-0

New class of compounds protect brain cells from traumatic brain injury

Prana's PBT2 receives FDA Orphan Drug designation for treatment of Huntington disease

Prana's PBT2 receives FDA Orphan Drug designation for treatment of Huntington disease

Two Vaccines Help Cut Bacteria That Cause Meningitis, Study Finds

Two new vaccines can reduce the spread of meningitis by reducing the number of meningitis-causing bacteria that people carry, according to a new study.

Researchers tested the two vaccines -- MenACWY-CRM and 4CMenB -- on volunteers aged 18 to 24. MenACWY-CRM cut meningitis-causing bacteria populations in the nose and throat by 39 percent and 4CMenB lowered those populations by 20 to 30 percent.

Two Vaccines Help Cut Bacteria That Cause Meningitis, Study Finds 

New Drug May Fight Serious Respiratory Virus in Infants

 An experimental drug shows promise in treating respiratory syncytial virus (RSV), a leading cause of pneumonia in infants, researchers report.

"We are finally making major progress in being able to treat human RSV infections -- the world's second leading cause of serious viral pneumonia, second only to influenza virus," said study author Dr. John DeVincenzo, a professor of pediatrics at the University of Tennessee College of Medicine in Memphis.

"There is no current treatment or vaccine for RSV pneumonia, and so patients were previously forced to get over the virus by themselves," he said. RSV is the leading cause of hospitalization among infants in the United States, the researchers noted.

In this small study of 140 adults, the drug, dubbed GS-5806, reduced the amount of the virus in the systems of those who received the medication.

"For the first time, we showed that once we reduce the amount of virus in patients, they very quickly started to feel better," DeVincenzo said.

New Drug May Fight Serious Respiratory Virus in Infants  

Drug Gives 'New Hope' Against Heart Failure, Expert Says

In a head-to-head comparison, an experimental drug was more effective than standard treatment at preventing deaths and hospitalizations in heart failure patients.

According to the study authors, the trial was stopped early because of the marked benefit of the new drug, dubbed LCZ696. [LCZ696 is an investigational combination drug consisting of two antihypertensives (blood pressure lowering drugs), valsartan (left below) and AHU-377 (right below), in a 1:1 mixture. It is being developed by Novartis. The combination is often described as a dual-acting angiotensin receptor-neprilysin inhibitor (ARNi)]

In the trial, 26.5 percent of those getting the standard medication, enalapril (Vasotec), either died or were hospitalized due to heart failure, compared with 21.8 percent of those on the new drug. Enalapril belongs to a class of blood pressure-lowering medications known as ACE inhibitors.

"LCZ696 could become the new gold standard, replacing ACE inhibitors," said lead researcher Dr. John McMurray, a professor of cardiology at the British Heart Foundation Cardiovascular Research Center at the University of Glasgow, in Scotland.

LCZ696 combines two blood pressure drugs -- an angiotensin II receptor blocker (ARB) and the neprilysin inhibitor known as sacubitril.

"We found that LCZ696 was superior to the gold-standard ACE inhibitor for heart failure -- an ACE inhibitor being the absolute cornerstone of treatment for this problem," he said.

Not only did LCZ696 beat enalapril, but it did that even when added to other treatments, McMurray noted.

"The new treatment was very well tolerated, with no significant safety concerns," he added.

Drug Gives 'New Hope' Against Heart Failure, Expert Says 

Synthesis produces new fungus-derived antibiotic

A fortuitous collaboration has led to the total synthesis of a recently discovered natural antibiotic. The laboratory recreation of a fungus-derived antibiotic, viridicatumtoxin B, may someday help bolster the fight against bacteria that evolve resistance to treatments in hospitals and clinics around the world.

As part of the process, Rice organic chemist K.C. Nicolaou and structural biologist Yousif Shamoo and their colleagues created and tested a number of variants of viridicatumtoxin B that could lead to the simplified synthesis of a new generation of more effective antibiotics.

The work reported this month in the Journal of the American Chemical Society (JACS) focused on a tetracycline discovered in 2008 by scientists who isolated small amounts from penicillium fungi. The yield wasn't nearly enough for extensive testing, but it provided a basis for the discoverers to analyze its structure through magnetic resonance imaging, Nicolaou said.

"We're inspired by molecules that are biologically active and have the potential to become medicines one day," he said.

The new discovery belongs to a class of antibiotics known as tetracyclines for their distinctive molecular structure. They proved potent  in  initial tests on
Gram-positive bacteria, so named for a staining technique to mark bacteria that are more susceptible to antibiotics than their Gram-negative counterparts.

The first tetracyclines, discovered in the late 1940s, ushered in a new class of
powerful antibacterial agents to treat high-mortality diseases,    among  them
anthrax and plague as well as such bacterial infections as chlamydia, syphilis
and Lyme disease.

To find new weapons, especially  against  "superbugs" that resist nearly all antibiotics, synthetic chemists pursue the complex  process  of  mimicking the
structures of effective natural molecules as they build drug candidates atom by atom.

"Tetracyclines are widespread antibiotics today, but bacteria are building resistance to a lot of them," Nicolaou said. "This new tetracycline is not plentiful in nature, so the only way we can make it available to study by biologists for its potential in medicine is to synthesize it in the laboratory."

Ref : http://pubs.acs.org/doi/abs/10.1021/ja506472u

Synthesis produces new fungus-derived antibiotic 

Experimental Drug Would Help Fight Ebola if Supply Increases, Study Finds - NYTimes.com

A new study provides strong evidence that the experimental drug given to two American aid workers stricken with Ebola in Africa really works and could make a difference in the current outbreak — if more of it could be produced.

In the study, all 18 monkeys exposed to a lethal dose of Ebola virus survived when given the drug, known as ZMapp, even when the treatment was started five days after infection, when the animals were already sick.

Moreover, the monkeys’ symptoms, such as excessive bleeding, rashes and signs of liver toxicity, eventually disappeared. By contrast, all three monkeys in the control group died.

Experts said these were the best monkey results reported to date for any Ebola drug, raising hopes that the drug will work in people.

Experimental Drug Would Help Fight Ebola if Supply Increases, Study Finds - NYTimes.com

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors

In continuation of my update on capsaicin

Researchers report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining the intestines of mice, triggering a reaction that ultimately reduces the risk of colorectal tumors....

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors  

Pesticide DDT linked to slow metabolism, obesity and diabetes, mouse study finds -- ScienceDaily

A new study in mice is the first to show that developmental exposure to DDT increases the risk of females later developing metabolic syndrome -- a cluster of conditions that include increased body fat, blood glucose, and cholesterol.

Pesticide DDT linked to slow metabolism, obesity and diabetes, mouse study finds  

Researchers uncover how malaria parasite becomes resistant to fosmidomycin drug

Researchers have uncovered a way the malaria parasite becomes resistant to an investigational drug. The discovery, at Washington University School of Medicine in St. Louis, also is relevant for other infectious diseases including bacterial infections and tuberculosis.

The study appears July 24 in Nature Communications.

Many organisms, including the parasite that causes malaria, make a class of molecules called isoprenoids, which play multiple roles in keeping organisms healthy, whether plants, animals or bacteria. In malaria, the investigational drug fosmidomycin blocks isoprenoid synthesis, killing the parasite. But over time the drug often becomes less effective.

"In trials testing fosmidomycin, the malaria parasite returned in more than half the children by the end of the study," said senior author Audrey R. Odom, MD, PhD, assistant professor of pediatrics. "We wanted to know how the parasite is getting around the drug. How can it manage to live even though the drug is suppressing these compounds that are necessary for life?"

Fosmidomycin, an antibiotic, is being evaluated against malaria in phase 3 clinical trials in combination with other antimalarial drugs.

Using next-generation sequencing technology, the research team compared the genetics of malaria parasites that responded to the drug to the genetics of malaria parasites that were resistant to it. With this approach, Odom and her colleagues found mutations in a gene called PfHAD1. With dysfunctional PfHAD1, malaria is resistant to fosmidomycin.

"The PfHAD1 protein is completely unstudied," Odom said. "It's a member of a larger family of proteins, and there are almost no biological functions assigned to them."

In malaria parasites, Odom's team showed that the PfHAD1 protein normally slows down the synthesis of isoprenoids. In other words, when present, PfHAD1 is doing the same job as the drug, slowing isoprenoid manufacturing. Since isoprenoids are necessary for life, it's not clear why the organism would purposefully slow down isoprenoid production.

Ref : http://www.nature.com/ncomms/2014/140724/ncomms5467/full/ncomms5467.html

Researchers uncover how malaria parasite becomes resistant to fosmidomycin drug