Harvoni Approved for Chronic Hepatitis C

In continuation of my update on  ledipasvir and sofosbuvir (Harvoni-combination pill) 

Harvoni, a daily pill that treats the most common form of hepatitis C, was approved by the U.S. Food and Drug Administration on Friday.

It's the first combination pill (ledipasvir and sofosbuvir) approved to treat the chronic infection, and the first medication that doesn't require that the antiviral drugs interferon or ribavirin be taken at the same time, the FDA said in a news release.

Both drugs in the combination pill interfere with the hepatitis C virus' ability to multiply. One of the drugs, sofosbuvir (Sovaldi) was approved in December 2013, while ledipasvir is a new antiviral, the agency said.

"With the development and approval of new treatments for hepatitis C virus, we are changing the treatment paradigm for Americans living with the disease," Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in the news release. "Until last year, the only available treatments for hepatitis C virus required administration with interferon and ribavirin. Now, patients and health care professionals have multiple treatment options, including a combination pill to help simplify treatment regimens."

One expert applauded Harvoni's approval.

"This is a giant step forward for people with [hepatitis C]. One pill, once daily, no interferon, no ribavirin and 94 to 99 percent cure! It moves the risk-benefit ratio needle way over toward benefit," said Dr. Douglas Dieterich, a professor of medicine in the division of liver diseases at The Mount Sinai Hospital in New York City.

However, price has been an issue with some of the new treatments for hepatitis C. For example, Sovaldi alone costs $1,000 a day and not all insurance companies cover the cost of treatment, experts have noted. Harvoni will cost $1,125 a pill, the Associated Press reported Friday.

Hepatitis C causes inflammation of the liver, which could spark other problems including diminished liver function (cirrhosis), scarring, liver cancer or liver failure. Most infected people aren't aware that they carry the virus until liver damage has occurred, the agency said.

Some 3.2 million Americans are believed to be infected with hepatitis C, the FDA said.

Harvoni was evaluated in three clinical studies involving more than 1,500 people who either hadn't been treated previously or hadn't responded to prior treatment. The most common side effects were fatigue and headache.

Harvoni Approved for Chronic Hepatitis C  

Impotence Drug Might Counter Common Gene Mutation in Type 2 Diabetes

In a small study, Swedish researchers found that the impotence drug yohimbine might help people with type 2 diabetes who have a particular gene mutation that lowers their insulin production.

Among 50 men and women with type 2 diabetes partially caused by a mutation in a gene called alpha(2A)-AR, those treated with yohimbine showed improved insulin production and lower blood sugar levels, compared with those receiving a placebo.

"If a diabetic patient carries the risk mutation, he or she is more sensitive to stress hormones such as adrenaline," said lead researcher Dr. Anders Rosengren, head of the translational diabetes research group at Lund University Diabetes Center in Malmo.

About 40 percent of patients with type 2 diabetes carry this mutation. "It is not that patients are more stressed, but that adrenaline suppresses insulin secretion," he added.

Rosengren explained how the drug overcomes the effects of the mutation: "It is like driving a car with the brakes constantly on. If you add yohimbine, you release the brake and the car -- the insulin-producing cells -- can go at normal speed. The cells secrete adequate amounts of insulin in response to sugar."

Impotence Drug Might Counter Common Gene Mutation in Type 2 Diabetes: Study 

FDA Approves Uceris (budesonide) Rectal Foam for Ulcerative Colitis

In continuation of my update on budesonide

Salix Pharmaceuticals, Ltd. announced that the Food and Drug Administration (FDA) has granted final approval for Uceris (budesonide) rectal foam for the induction of remission in patients with active mild-to-moderate distal ulcerative colitis (UC) extending up to 40cm from the anal verge. The foam is a rectally administered corticosteroid that overcomes treatment limitations associated with currently approved therapies which are often ineffective due to insufficient distribution of active drug to the distal colon. On September 15, 2014 the FDA tentatively approved Uceris rectal foam pending expiration of the 45-day waiting period described in section 505( c )(3)( C ) of the Federal Food, Drug and Cosmetic Act. The waiting period has expired and the FDA has granted Uceris rectal foam final approval as of October 7, 2014.

FDA Approves Uceris (budesonide) Rectal Foam for Ulcerative Colitis

Attacking type 2 diabetes from a new direction with encouraging results

Type 2 diabetes affects  an estimated   28  million  Americans  according  to  the  American  Diabetes association, but medications now  available  only  treat  symptoms,  not  the root  cause of the disease.    New research from Rutgers shows promising evidence that     a  modified form of a different drug, niclosamide     now used to eliminate    intestinal parasites   may       hold the key to battling the disease at its source.

Ref : http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3699.html

Attacking type 2 diabetes from a new direction with encouraging results  

First pictures of BRCA2 protein show how it works to repair DNA

In continuation of my update on BRCA2 

Scientists have taken pictures of the BRCA2 protein for the first time, showing how it works to repair damaged DNA. The findings showed that each pair of BRCA2 proteins binds two sets of RAD51 that run in opposite directions. This allows it to work on strands of broken DNA that point in either direction. They also show that BRCA2's job is to help RAD51 form short filaments at multiple sites along the DNA, presumably to increase the efficiency of establishing longer filaments required to search for matching strands.

Researchers at Imperial College London and the Cancer Research UK London Research Institute purified the protein and used electron microscopy to reveal its structure and how it interacts with other proteins and DNA. The results are published today in Nature Structural and Molecular Biology.

Around one in 1000 people in the UK have a mutation in the BRCA2 gene. The lifetime risk of breast cancer for women with BRCA2 mutations is 40 to 85 per cent, depending on the mutation, compared with around 12 per cent for the general population. Many women who test positive for BRCA1 and BRCA2 mutations choose to undergo surgery to reduce their risk of breast cancer. Mutations can also raise the risk of other cancers, such as ovarian, prostate and pancreatic cancer.

The BRCA1 and BRCA2 genes encode proteins involved in DNA repair. The DNA in our cells undergoes damage thousands of times a day, caused by toxic chemicals, metabolic by-products and ultraviolet radiation. Repair mechanisms correct most of this damage, but unrepaired damage can lead to cancer.

The study was led by Professor Xiaodong Zhang from the Department of Medicine at Imperial College London and Dr Stephen West at the London Research Institute.

"This study improves our understanding of a fundamental cause of cancer," said Professor Zhang, a Wellcome Trust Senior Investigator. "It's our first view of how the protein looks and how it works, and it gives us a platform to design new experiments to probe its mechanism in greater detail.

"Once we have added more detail to the picture, we can design ways to correct defects in BRCA2 and help cells repair DNA more effectively to prevent cancer. We can also think about how to make the repair process less effective in cancer cells, so that they die."

The study found that BRCA2 proteins work in pairs -- which the researchers found surprising since BRCA2 is one of the largest proteins in the cell.

BRCA2 works in partnership with another protein called RAD51. BRCA2 helps RAD51 molecules to assemble on strands of broken DNA and form filaments. The RAD51 filaments then search for matching strands of DNA in order to repair the break.

The findings showed that each pair of BRCA2 proteins binds two sets of RAD51 that run in opposite directions. This allows it to work on strands of broken DNA that point in either direction. They also show that BRCA2's job is to help RAD51 form short filaments at multiple sites along the DNA, presumably to increase the efficiency of establishing longer filaments required to search for matching strands.

Ref : http://dx.doi.org/10.1038/nsmb.2899

First pictures of BRCA2 protein show how it works to repair DNA  

'Programmable' antibiotic harnesses an enzyme to attack drug-resistant microbes

Rockefeller University researchers colonized mouse skin with a mix of bacterial cells, some resistant to the antibiotic kanamycin. They made the resistant cells glow (left) and treated the mix with an enzyme that targeted and killed off most resistant cells (right).

Conventional antibiotics are indiscriminate about what they kill, a trait that can lead to complications for patients and can contribute to the growing problems of antibiotic resistance. But a a 'programmable' antibiotic would selectively target only the bad bugs, particularly those harboring antibiotic resistance genes, and leave beneficial microbes alone.

Researchers at Rockefeller University and their collaborators are working on a smarter antibiotic. And in research to be published October 5 in Nature Biotechnology, the team describes a 'programmable' antibiotic technique that selectively targets the bad bugs, particularly those harboring antibiotic resistance genes, while leaving other, more innocent microbes alone.

"In experiments, we succeeded in instructing a bacterial enzyme, known as Cas9, to target a particular DNA sequence and cut it up," says lead researcher Luciano Marraffini, head of the Laboratory of Bacteriology. "This selective approach leaves the healthy microbial community intact, and our experiments suggest that by doing so you can keep resistance in check and so prevent certain types of secondary infections, eliminating two serious hazards associated with treatment by classical antibiotics."

The new approach could, for instance, reduce the risk of C. diff, a severe infection of the colon, caused by the Clostridium difficile bacterium, that is associated with prolonged courses of harsh antibiotics and is a growing public health concern.

The Cas9 enzyme is part of a defense system that bacteria use to protect themselves against viruses. The team coopted this bacterial version of an immune system, known as a CRISPR (clustered regularly interspaced short palindromic repeats) system and turned it against some of the microbes. CRISPR systems contain unique genetic sequences called spacers that correspond to sequences in viruses. CRISPR-associated enzymes, including Cas9, use these spacer sequences as guides to identify and destroy viral invaders.

The researchers were able to direct Cas9 at targets of their choosing by engineering spacer sequences to match bacterial genes then inserting these sequences into a cell along with the Cas9 gene. The cell's own machinery then turns on the system. Depending on the location of the target in a bacterial cell, Cas9 may kill the cell or it may eradicate the target gene. In some cases, a treatment may prevent a cell from acquiring resistance, they found.

"We previously showed that if Cas9 is programmed with a target from a bacterial genome, it will kill the bacteria. Building on that work, we selected guide sequences that enabled us to selectively kill a particular strain of microbe from within a mixed population," says first author David Bikard, a former Rockefeller postdoc who is now at the Pasteur Institute in Paris.

'Programmable' antibiotic harnesses an enzyme to attack drug-resistant microbes 

Omega-3 fatty acids may prevent some forms of depression

Omega-3 fatty acids may prevent some forms of depression 

FDA Approves New Obesity Drug Contrave

In continuation of my update on Contrave

The U.S. Food and Drug Administration's approval of a new weight-loss drug on Wednesday marks the third time the agency has given its blessing to a new diet medication since 2012.

Called Contrave, the medicine is a combination of two approved drugs: naltrexone, which treats alcohol and drug addiction, and bupropion, which treats depression and seasonal affective disorder and is used to help smokers quit.

The agency said in a news release that Contrave can be used by obese adults and by overweight adults who have at least one other weight-related condition or illness, such as high blood pressure or type 2 diabetes.

According to the U.S. Centers for Disease Control and Prevention, more than one-third of adults in the United States are obese, the FDA said in its news release.

"Obesity continues to be a major public health concern," said Dr. Jean-Marc Guettier, director of the division of metabolism and endocrinology products in the FDA's Center for Drug Evaluation and Research. "When used as directed in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, Contrave provides another treatment option for chronic weight management."

FDA Approves New Obesity Drug Contrave  

Anamorelin drug safe and well tolerated in advanced non-small cell lung cancer, Phase III trial reveals

A new drug, anamorelin, improves appetite and body mass in patients with advanced lung cancer who are suffering cancer anorexia and cachexia, according to phase III data presented at the ESMO 2014 Congress in Madrid, Spain.

"Anorexia and cachexia are among the most troubling and distressing symptoms of advanced cancer, for both patients and their families," says the study's principal investigator, Dr Jennifer Temel from the Department of Medicine, Massachusetts General Hospital, Boston, USA.

Symptoms of the wasting syndrome can include a loss of weight and muscles, together with fatigue, weakness, and loss of appetite. The condition is very common in patients with advanced lung cancer. Anamorelin aims to address the symptoms by mimicking the effects of the so-called "hunger hormone" ghrelin, which is secreted by the stomach.

The large, randomized controlled ROMANA 1 and 2 trials are the first phase III studies examining the impact of anamorelin on anorexia-cachexia in patients with advanced lung cancer.

In the ROMANA studies, patients with unresectable stage III or IV non-small cell lung cancer with cachexia were randomized to receive either 100 mg anamorelin or placebo, given orally each day for 12 weeks.

Among 484 participants in ROMANA 1, those taking anamorelin experienced a median increase in lean body mass of 1.10 kg in 12 weeks, compared to a loss of 0.44 kg for those taking placebo. Body weight increased in the anamorelin arm by an average of 2.2 kg, compared to 0.14 kg in the placebo arm of the study. Patient symptoms or concerns regarding anorexia-cachexia, including appetite, also significantly improved over 12 weeks in patients taking anamorelin. The most frequent drug-related adverse events included hyperglycemia and nausea.

In ROMANA 2, 495 participants with advanced non-small cell lung cancer experiened similar benefits. Body weight increased by 0.95 kg on average, compared to a loss of 0.57 kg for those receiving placebo, and patient symptoms/concerns regarding anorexia-cachexia significantly improved over 12 weeks.

Patients receiving anamorelin did not experience improvements in their muscle strength, as measured by hand grip strength, although Temel notes that particular test can be difficult to administer in this patient population.

Anamorelin drug safe and well tolerated in advanced non-small cell lung cancer, Phase III trial reveals

Oral afatinib significantly improves progression-free survival in patients with head and neck cancer

The tyrosine kinase inhibitor afatinib significantly improved progression-free survival compared to methotrexate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy, the results of a phase III trial show.

Presented at the ESMO 2014 Congress in Madrid, the Lux-Head & Neck 1 trial showed that patients who received treatment with 40 mg/day oral afatinib had a 20% reduction in risk of progression or death compared to patients who received methotrexate, with a median progression-free survival of 2.6 months.

"The improvement in progression-free survival was associated with a significant delayed worsening of symptoms (such as pain, swallowing and global health status) versus chemotherapy. Patients treated with afatinib had less pain over time than patients treated with methotrexate. "These are important outcomes for patients with these conditions," notes study author Dr Jean-Pascal Machiels, a medical oncologist at Institut Roi Albert II, Cliniques Universitaires St. Luc, in Brussels, Belgium.

Recurrent or metastatic squamous cell carcinoma of the head and neck often has a poor outcome, Machiels explains. "This is a poor prognosis population and a disease that does not get enough attention from the scientific community, because this group of patients often has severe co-morbidities and social problems such as alcoholism and tobacco use."

"Frequently these patients have a relapse in the head and neck area. This location is responsible of many symptoms that are difficult to palliate: pain, breath disorder and swallowing difficulties."

Afatinib is a compound that irreversibly blocks the ErbB family of cell surface receptors, which includes epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), HER3 and HER4. Around 90% of squamous cell carcinomas of the head and neck overexpress EGFR.

Oral afatinib significantly improves progression-free survival in patients with head and neck cancer

Isavuconazole demonstrates successful outcomes in treatment of mucormycosis

In continuation of my update on Isavuconazole

Isavuconazole demonstrates successful outcomes in treatment of mucormycosis

Phase III trial: Rolapitant lessens chemotherapy-induced nausea and vomiting

Rolapitant reduces nausea and vomiting in patients receiving cisplatin-based chemotherapy, according to the results of a phase III trial presented for the first time today at the ESMO 2014 Congress in Madrid, Spain.

Dr Martin Chasen, lead author and medical director, Palliative Care, Ottawa Hospital Cancer Centre, Canada, said: "This agent makes a significant difference in the way people tolerate their chemotherapy. Patients experienced no loss in quality of life and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin."

"We must treat nausea and vomiting, not just the cancer," added Chasen, emphasising that some patients are extremely sensitive to cisplatin effects and recalling that he had one or two patients with curable cancers who refused treatment after one round of cisplatin. "They preferred to die," he said.

The phase III trial investigated rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation. The multicentre trial randomised 532 patients 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to cisplatin-based chemotherapy.

Phase III trial: Rolapitant lessens chemotherapy-induced nausea and vomiting

Crizotinib drug effectively halts growth of ROS1-positive lung tumors

In continuation of my update on crizotinib

Treatment with the targeted therapy drug crizotinib effectively halts the growth of lung tumors driven by rearrangements of the ROS1 gene. In an article receiving Online First publication in the New England Journal of Medicine to coincide with a presentation at the European Society for Medical Oncology meeting, an international research team reports that crizotinib treatment led to significant tumor shrinkage in 36 of 50 study participants and suppressed tumor growth in another 9.

"Prior to this study, there were a handful of reports describing marked responses to crizotinib in individual patients with ROS1-positive lung tumors," says Alice Shaw, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center, lead author of the NEJM report. "This is the first definitive study to establish crizotinib's activity in a large group of patients with ROS1-positive lung cancer and to confirm that ROS1 is a bona fide therapeutic target in those patients."

Crizotinib currently is FDA-approved to treat non-small-cell lung cancers (NSCLC) driven by rearrangments in the ALK gene, which make up around 4 percent of cases. An MGH Cancer Center report published in 2012 reported that 1 to 2 percent of NSCLCs are driven by rearrangements in ROS1, which encodes a protein with significant structural similarities to that encoded by the ALK gene.

Crizotinib drug effectively halts growth of ROS1-positive lung tumors

FDA Approves Iluvien for Diabetic Macular Edema

pSivida Corp., a leader in the development of sustained release, drug delivery products for treating eye diseases, today announced that the U.S. Food and Drug Administration (FDA) has approved Iluvien for the treatment of diabetic macular edema (DME). It is indicated for patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure (IOP). A single injection of the Iluvien micro-insert provides sustained treatment of DME for 36 months. Approximately 560,000 people in the U.S. are estimated to have clinically significant DME, the most frequent cause of vision loss in individuals with diabetes and the leading cause of blindness in young and middle-aged adults in developed countries. Iluvien is expected to be commercially available in the U.S. in early 2015.

FDA Approves Iluvien for Diabetic Macular Edema

Candidate H7N9 avian flu vaccine works better with adjuvant

Candidate H7N9 avian flu vaccine works better with adjuvant