Triphase's marizomib receives FDA orphan drug designation for treatment of multiple myeloma

Salinosporamide A (Marizomib) is a potent proteasome inhibitor used as an anticancer agent that recently entered phase I human clinical trials for the treatment of multiple myeloma only three years after its discovery. This novel marine natural product is produced by the recently described obligate marine bacteria Salinispora tropica and Salinispora arenicola, which are found in ocean sediment. Salinosporamide A belongs to a family of compounds, known collectively as salinosporamides, which possess a densely functionalized γ-lactam-β-lactone bicyclic core.

Triphase Accelerator Corporation recentlyannounced that marizomib, its novel, potent proteasome inhibitor, has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA)'s Office of Orphan Products Development for the treatment of multiple myeloma. The orphan drug designation will provide Triphase with 7-year marketing exclusivity for marizomib and other benefits upon FDA approval.

"We are pleased that the FDA has granted orphan drug designation for the development of marizomib to benefit patients with multiple myeloma," said Frank Stonebanks, founder, president and CEO of Triphase. "While patients with refractory multiple myeloma are living longer and better lives as a result of medical innovation, there is still a need for new treatment options. We are excited to move forward with the development of marizomib, a potential best-in-class agent, and hope to advance the treatment paradigm that will turn this once acute disease into a long-term manageable disease."

Triphase's marizomib receives FDA orphan drug designation for treatment of multiple myeloma

Astellas Pharma to exclusively commercialize isavuconazole in the U.S. and Canada

Isavuconazole (BAL4815) is a triazole antifungal. Its prodrug, isavuconazonium sulfate (BAL8557) is currently in two Phase IIIclinical trials (SECURE and VITAL), the results of which are expected in the second half of 2013.

On May 28, 2013, Basilea Pharmaceutica, the maker of the drug, announced it had been granted orphan drug status by the U.S. Food and Drug Administration (FDA).

Now Astellas Pharma Inc. (Tokyo:4503, "Astellas") announced today that the company has amended the License, Co-Development and Co-Promotion Agreement on isavuconazole under co-development with Basilea Pharmaceutica Ltd. ("Basilea"). Based on this amendment, the territories subject to the License Agreement have been changed to reflect that Astellas will be responsible for all regulatory filings and will exclusively commercialize and assume full responsibility for manufacturing isavuconazole in the U.S. and Canada.

Astellas Pharma to exclusively commercialize isavuconazole in the U.S. and Canada

Researchers discover novel treatments for psoriasis that are likely to cause fewer side effects

In the article in Science Translational Medicine, which features Juan Guinea-Viniegra as the lead author, the authors state that: "blocking miR-21 could offer advantages over current treatments given that the efficiency obtained is the same and the side effects are probably reduced". The authors highlight that in the mouse model and in patient samples transplanted into mice this new strategy "shows a significant therapeutic response".

Researchers discover novel treatments for psoriasis that are likely to cause fewer side effects

Adocia reports positive preliminary results for first clinical trial of BioChaperone Combo

Adocia reports positive preliminary results for first clinical trial of BioChaperone Combo

FDA Accepts Filing of NDA for IV Antibiotic Oritavancin with Priority Review

FDA Accepts Filing of NDA for IV Antibiotic Oritavancin with Priority Review

Oritavancin (INN, also known as LY333328) is a novel semi-synthetic glycopeptide antibiotic being developed for the treatment of serious Gram-positive infections. Originally discovered and developed by Eli Lilly, oritavancin was acquired by InterMune in 2001 and then by Targanta Therapeutics in late 2005.

In Dec 2008 the FDA declined to approve it, and an EU application was withdrawn. In 2009 the development rights were acquired by The Medicine Co. who are running clinical trials for a possible new FDA application in 2013

Now...

Small molecules stop cervical cancer virus assembling

Researchers in China have disrupted the life cycle of the leading cause of cervical cancer – the human papilloma virus – using a macrocyclic molecule called a pillarene. The team hope their findings will offer new prophylactic avenues against the virus.

The pillarene derivative, CP5A, was tested as it is known to have high water solubility and show selective binding towards basic amino acids, like l-Lysine, l-arginine and l-histidine. Because of these properties, CP5A binds to the exposed basic amino acids in protein L1, preventing pentamer formation, and therefore stopping the creation of viral particles.

The team hope to screen other small molecules to find inhibitors for more specific binding sites on the interface between L1 and L2. Their long term aim is to use one of these to produce a HPV vaccine.

Ref : http://pubs.rsc.org/en/Content/ArticleLanding/2014/CC/c3cc49789e#!divAbstract

Small molecules stop cervical cancer virus assembling | Chemistry World

Old FDA-approved drugs may hold promise for treatment of rare, drug-resistant cancer

After studying how samples of GIST responded to various concentrations of the 89 drugs in the laboratory, Dr. Duensing and her colleagues identified 37 compounds that showed some anticancer activity in at least one of the concentrations tested. Importantly, they noted that the most promising candidates all belonged to only two major drug classes: inhibitors of gene transcription and so-called topoisomerase II inhibitors. Based on these findings, the research team selected the two most promising compounds for further testing - gene transcription inhibitor mithramycin A (left structure below) , which is in clinical trials to treat Ewing sarcoma, and topoisomerase II inhibitor mitoxantrone (beow right structure), which is used in metastatic breast cancer and leukemia.

Both drugs were highly effective in fighting GIST in laboratory tests. Moreover, the mechanism of action of each drug was linked to the specific underlying biology of these tumors.

"These are very encouraging results," said Dr. Duensing. "The next step will be moving our findings to clinical exploration to see if the results we found in the lab hold up in patients."

Old FDA-approved drugs may hold promise for treatment of rare, drug-resistant cancer

Ref : http://www.upmc.com/media/NewsReleases/2014/Pages/upci-scientists-detect-therapy-for-drug-resistant-cancer.aspx

Researchers create promising compound for cancer treatment

Researchers create promising compound for cancer treatment

FDA-approved drug pregabalin effectively treats RLS symptoms with less side effects

In continuation of my update on pregabalin

A report in the Feb. 13 New England Journal of Medicine confirms previous studies suggesting that long-term treatment with the type of drugs commonly prescribed to treat restless leg syndrome (RLS) can cause a serious worsening of the condition in some patients. The year-long study from a multi-institutional research team found that pregabalin - which is FDA-approved to treat nerve pain, seizures, and other conditions - was effective in reducing RLS symptoms and was much less likely to cause symptom worsening than pramipexole, one of several drugs that activate the dopamine neurotransmission system and are FDA approved for treatment of RLS.

"Our key finding is that dopaminergic drugs, while very effective for many people with RLS, can worsen symptoms in some patients over time, while non-dopaminergic pregabalin is not associated with this disturbing side effect," says John Winkelman, MD, PhD, of the Massachusetts General Hospital Department of Psychiatry, senior author of the study. "Those treating RLS patients with dopaminergic drugs need to be aware of this common complication and exercise caution if their symptoms worsen."

FDA-approved drug pregabalin effectively treats RLS symptoms with less side effects

Melatonin shows potential to slow tumor growth in certain breast cancers

An  early stage study shows melatonin   a hormone that regulates the body's sleep and awake cycles  may have the potential to help slow the growth of certain breast cancer tumors, according to researchers from Henry Ford Hospital in Detroit and Foundation for Research Support of the State of São Paulo.

Melatonin shows potential to slow tumor growth in certain breast cancers  

Geranium extracts inhibit HIV-1

Extracts of the geranium plant Pelargonium sidoides inactivate human immunodeficiency virus type 1 (HIV-1) and prevent the virus from invading human cells. Scientists report that these extracts represent a potential new class of anti-HIV-1 agents for the treatment of AIDS.

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0087487

Geranium extracts inhibit HIV-1  

Biotechdaily - Nilotinib Enhances Toxic Protein Removal from Parkinson's Disease Neurons

In continuation of my update on Nilotinib

The anticancer drug nilotinib induces clearance of the toxic protein alpha-synuclein from   neurons in a mouse model of Parkinson's disease and ameliorates symptoms of the disease.

Investigators at Georgetown University Medical Center (Washington DC, USA) worked with a mouse model of Parkinson’s disease. They reported in the May 10, 2013, online edition of the journal Human Molecular Genetics that lentiviral transfection of the gene encoding alpha-synuclein into the mouse SN lead to activation (phosphorylation) of the tyrosine kinase Abl and that lentiviral transfection of the gene encoding Abl increased alpha-synuclein levels, which exacerbated the disease. Administration of the tyrosine-kinase inhibitor nilotinib decreased Abl activity and increased autophagic clearance of alpha-synuclein into lysosomes in transgenic and lentiviral gene-transfer models.

The drug nilotinib was approved as Tasigna in the USA and the EU for drug-resistant chronic myelogenous leukemia (CML). In 2006, a Phase I clinical trial found that nilotinib had a relatively favorable safety profile and showed activity in cases of CML resistant to treatment with imatinib (Gleevec [USA]/ Glivec [Europe, Australia, and Latin America]), another tyrosine kinase inhibitor currently used as a first-line treatment. In that study, 92% of patients (already resistant or unresponsive to imatinib) achieved a normal white blood cell counts after five months of treatment.

In the current study, nilotinib, which enters the brain within [US] Food and Drug Administration approved doses, led to autophagic degradation of alpha-synuclein, protection of SN neurons and improvement of motor performance in the Parkinson’s disease mice.

 
"No one has tried anything like this before," said senior author Dr. Charbel E-H Moussa, assistant professor of neuroscience at the Georgetown University Medical Center. "This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell. By clearing intracellular proteins, the drug prevents their accumulation in pathological inclusions called Lewy bodies and/or tangles, and also prevents amyloid secretion into the extracellular space between neurons, so proteins do not form toxic clumps or plaques in the brain."

"The doses used to treat CML are high enough that the drug pushes cells to chew up their own internal organelles, causing self-cannibalization and cell death," said Dr. Moussa. "We reasoned that small doses—for these mice, an equivalent to 1% of the dose used in humans—would turn on just enough autophagy in neurons that the cells would clear malfunctioning proteins, and nothing else. We successfully tested this for several diseases models that have an accumulation of intracellular protein. It gets rid of alpha-synuclein and tau in a number of movement disorders, such as Parkinson's disease as well as Lewy body dementia."

Biotechdaily - Nilotinib Enhances Toxic Protein Removal from Parkinson's Disease Neurons

New Hepatitis C Drug Sovaldi Approved by FDA

A new hepatitis C drug that can be taken as a pill once a day was approved by the U.S. Food and Drug Administration on Friday.

The drug, called Sovaldi and made by Calif.-based Gilead Sciences Inc., works faster and should be much simpler to take for the millions of Americans who have the virus, which can destroy the liver if left untreated.

The FDA said in a statement that Sovaldi is to be taken with older drugs to treat the main forms of hepatitis C. The agency added that 3.2 million Americans have the disease, and people born between 1945 and 1965 are five times more likely to be infected.

Current treatments can take almost a year to beat back the virus, and involve weekly injections of the drug interferon, which can cause diarrhea and flu-like symptoms, the FDA said. Only about 75 percent of patients are cured with current treatments. In clinical trials, Sovaldi cured close to 90 percent of patients in just 12 weeks, when combined with the standard treatment.

Sovaldi (sofosbuvir) is the second hepatitis C drug to be approved by the FDA in the past two weeks. In November, the agency gave its blessing to Olysio (simeprevir), made by Janssen Pharmaceuticals, of Raritan, N.J.

Symptoms of hepatitis C disease may not appear until two or three decades after infection, though the virus can cause liver failure, cirrhosis and cancer, the FDA said.

New Hepatitis C Drug Sovaldi Approved by FDA - Drugs.com MedNews

Experimental Drug Pritelivir Shows Promise for Genital Herpes Treatment

An experimental drug could eventually offer a new treatment option for genital herpes, a common and incurable sexually transmitted infection, researchers report.

In a small study, researchers found that the drug -- called pritelivir -- substantially curbed "viral shedding" in people with genital herpes. That means it decreased the amount of time the virus was active and potentially transmissible to patients' sexual partners.

The findings, reported in the Jan. 16 issue of the New England Journal of Medicine, are based on 156 patients followed for just four weeks. Experts cautioned that the study is preliminary and offers a "proof of concept."

Still, they said, the results are important because pritelivir is the first in a new class of drugs that works differently than existing medications for genital herpes. The hope is that pritelivir will be better at preventing transmission of the virus.

"There was a fairly dramatic decrease in the probability of viral shedding in this study," said Dr. Richard Whitley, an infectious disease expert at the University of Alabama at Birmingham.

There is still a lot of research to be done, said Whitley, who wrote an editorial published with the study. But he said it's good news that drugs that work in new ways are under development.

"We're at the beginning of a new era" in genital herpes treatment, Whitley said.

Experimental Drug Pritelivir Shows Promise for Genital Herpes Treatment

Potential drug targets for early onset glaucoma

Using a novel high-throughput screening process, scientists have for the first time identified molecules with the potential to block the accumulation of a toxic eye protein that can lead to early onset of glaucoma.

Glaucoma is a group of diseases that can damage the eye's optic nerve and cause vision loss and blindness. Elevated eye pressure is the main risk factor for optic nerve damage.

Researchers have implicated a mutant form of a protein called myocilin as a possible root cause of this increased eye pressure. Mutant myocilin is toxic to the cells in the part of the eye that regulates pressure. These genetically inherited mutants of myocilin clump together in the front of the eye, preventing fluid flow out of the eye, which then raises eye pressure. This cascade of events can lead to early onset-glaucoma, which affects several million people from childhood to age 35.

To find molecules that bind to mutant myocilin and block its aggregation, researchers designed a simple, high-throughput assay and then screened a library of compounds. They identified two molecules with potential for future drug development to treat early onset glaucoma.

"These are really the first potential drug targets for glaucoma," said Raquel Lieberman, an associate professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology in Atlanta, whose lab led the research.

Lieberman presented her findings on January 20 at the Society for Laboratory Automation and Screening conference in San Diego, Calif.

The study was published on Nov. 26, 2013, in the journal ACS Chemical Biology. The National Institutes of Health and the Pew Scholar in Biomedical Sciences program provided support for the research. The work was a collaboration involving Georgia Tech, Emory University and the University of South Florida.

Ref : 1. http://pubs.acs.org/doi/abs/10.1021/cb4007776

         2. http://www.sciencedirect.com/science/article/pii/S0022283613007407

Potential drug targets for early onset glaucoma