GlaxoSmithKline receives CHMP positive opinion for REVOLADE

In continuation of my update on Eltrombopag

Eltrombopag (codenamed SB-497115-GR) is a medication that has been developed for conditions that lead to thrombocytopenia (abnormally low platelet counts). It is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. Designated an orphan drugin the USA and European Union, it is being manufactured and marketed by GlaxoSmithKline under the trade name Promacta in the USA and will be marketed as Revolade in the EU. Eltrombopag was approved by the U.S. Food and Drug Administration on November 20, 2008....

GlaxoSmithKline receives CHMP positive opinion for REVOLADE

Rapamycin: Limited anti-aging effects

In continuation of my update on Rapamycin

The drug rapamycin is known to increase lifespan in mice. Whether rapamycin slows down aging, however, remains unclear. A team of researchers from the German Center for Neurodegenerative Diseases (DZNE) and the Helmholtz Zentrum München has now found that rapamycin extends lifespan -- but its impact on aging itself is limited. The life-extending effect seems to be related to rapamycin's suppression of tumors, which represent the main causes of death in these mouse strains....

Ref : http://www.jci.org/articles/view/67674

Rapamycin: Limited anti-aging effects

Teduglutide offers relief for patients with short-bowel syndrome

 

In continuation of my update on Teduglutide

Teduglutide (brand names Gattex and Revestive) is a 36-membered polypeptide and glucagon-like peptide-2 analog that is used for the treatment of short bowel syndrome. It works by promoting mucosal growth and possibly restoring gastric emptying and secretion. In Europe it is marketed under the brand Revestive by Nycomed. It was approved by the United States under the name Gattex on December 21, 2012...

Teduglutide offers relief for patients with short-bowel syndrome

Chelsea Therapeutics Announces FDA Acceptance of Northera (droxidopa) NDA Resubmission

In continuation of my update on droxidopa.....

Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) today announced that the U.S. Food and Drug Administration (FDA) has acknowledged receipt of the New Drug Application (NDA) resubmission seeking approval to market NORTHERA(TM) (droxidopa), an orally active synthetic precursor of norepinephrine, for the treatment of symptomatic neurogenic orthostatic hypotension (NOH) in patients with primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure), dopamine beta hydroxylase deficiency and non-diabetic autonomic neuropathy. The FDA has deemed the resubmission a complete response to its March 28, 2012 Complete Response Letter and assigned a new Prescription Drug User Fee Act (PDUFA) goal date of January 3, 2014.

Chelsea Therapeutics Announces FDA Acceptance of Northera (droxidopa) NDA Resubmission

Cheaper anti-cancer drug as effective as expensive drug in treating most common cause of blindness in older adults

Results of a two-year trial, led by Queen's scientist Professor Usha Chakravarthy, and published in The Lancet today (Friday 19 July), show that two drug treatments Lucentis and Avastinare equally effective in treating neovascular or wet age-related macular degeneration (wet AMD)....

Ref : http://www.sciencedirect.com/science/article/pii/S0140673613615019

Cheaper anti-cancer drug as effective as expensive drug in treating most common cause of blindness in older adults

New drugs to find the right target to fight Alzheimer's disease

A favorite Alzheimer's target: gamma secretase

The two next-generation classes of compound that are currently in clinical trials target an enzyme that cuts APP, known as gamma secretase. Until now, our understanding of the mechanism involved has been lacking. But with this work, the EPFL researchers were able to shed some more light on it by determining how the drug compounds affect gamma secretase and its cutting activity.

In most forms of Alzheimer's, abnormally large quantities of the long amyloid peptide 42 -- named like that because it contains 42 amino acids  are formed. The drug compounds change the location where gamma secretase cuts the APP protein, thus producing amyloid peptide 38 instead of 42, which is shorter and does not aggregate into neurotoxic plaques.

Compared to previous therapeutic efforts, this is considerable progress. In 2010, Phase III clinical trials had to be abandoned, because the compound being tested inhibited gamma-secretase's function across the board, meaning that the enzyme was also deactivated in essential cellular differentiation processes, resulting to side-effects like in gastrointestinal bleeding and skin cancer.

"Scientists have been trying to target gamma secretase to treat Alzheimer's for over a decade," explains Patrick Fraering, senior author on the study and Merck Serono Chair of Neurosciences at EPFL. "Our work suggests that next-generation molecules, by modulating rather than inhibiting the enzyme, could have few, if any, side-effects. It is tremendously encouraging."

Ref : http://www.nature.com/ncomms/2013/130802/ncomms3246/full/ncomms3246.html

New drugs to find the right target to fight Alzheimer's disease

Necrostatin-1 counteracts aluminum's neurotoxic effects

we know that, Necrostatin-1 inhibits necroptosis, a non-apoptotic cell death pathway. Inhibits the loss of mitochondrial membrane potential in TNFα-treated Jurkat cells (EC50=490 nM). Does not inhibit FAS-induced apoptosis and has no effect on apoptotic morphology. It displays a pronounced protective effect in a mouse model of ischemic brain injury and inhibits myocardial cell death. Inhibits RIP1 kinase the key upstream kinase involved in the activation of necroptosis (EC50=180nM).

Ivestigators have linked aluminum accumulation in the brain as a possible contributing factor to neurodegenerative disorders such as Alzheimer's disease. A new study published in Restorative Neurology and Neuroscience sheds light on the mechanism underlying aluminum-induced neuronal cell death and identifies necrostatin-1 as a substance which counteracts several of aluminum's neurotoxic effects.

Ref : http://iospress.metapress.com/content/h81617j3542x6487/?p=cfdaeabe671d4941ba8ae36ae55c6c5f&pi=0

Necrostatin-1 counteracts aluminum's neurotoxic effects

Acid reflux drug may cause heart disease, study suggests

In human tissue and mouse models, the researchers found PPIs (proton pump inhibitors) caused the constriction of blood vessels. If taken regularly, PPIs could lead to a variety of cardiovascular problems over time, including hypertension and a weakened heart. In the paper, the scientists call for a broad, large-scale study to determine whether PPIs are dangerous.

"The surprising effect that PPIs may impair vascular health needs further investigation," said John Cooke, M.D., Ph.D., the study's principal investigator. "Our work is consistent with previous reports that PPIs may increase the risk of a second heart attack in people that have been hospitalized with an acute coronary syndrome. Patients taking PPIs may wish to speak to their doctors about switching to another drug to protect their stomachs, if they are at risk for a heart attack."

Commonly used proton pump inhibitors in the United States are lansoprazole (below left) and omeprazole (below right), 

and these drugs are purchasable over the counter as brands or generics. The FDA estimates about 1 in 14 Americans has used them. In 2009, PPIs were the third-most taken type of drug in the U.S., accounting for $13 billion in sales. PPIs are used to treat a wide range of disorders, including gastroesophageal reflux disease, or GERD, infection by the ulcer-causing Helicobacter pylori, Zollinger-Ellison syndrome, and Barrett's esophagus.

Recent studies of proton pump inhibitors use by people who've already experienced severe cardiovascular events have raised concern about the anti-reflux drugs, at least for this subgroup of patients, said Cooke, chair of the Department of Cardiovascular Sciences and director of the Center for Cardiovascular Regeneration at Houston Methodist DeBakey Heart & Vascular Center.

PPIs are initially inert. After oral consumption, they are activated by specialized cells in the stomach. Once active, the molecules suppress the movement of protons into the intestine, which reduces the amount of acid present there and in the stomach.

In mouse models and cultures of human endothelial cells, Cooke and lead author Yohannes Ghebramariam, Ph.D., found that PPIs suppressed the enzyme DDAH, dimethylarginine dimethylaminohydrolase. That caused an increase in the blood levels of ADMA (asymmetric dimethylarginine), an important chemical messenger. They found ADMA in turn suppressed the production of another chemical messenger, nitric oxide, or NO, proven by 1998 Nobel Prize winners Furchgott, Ignarro, and Murad to impact cardiovascular function. Quantitative studies in mouse models showed animals fed PPIs were more likely than controls to have tense vascular tissue.

"We found that PPIs interfere with the ability of blood vessels to relax," said Ghebremariam, a Houston Methodist molecular biologist. "PPIs have this adverse effect by reducing the ability of human blood vessels to generate nitric oxide. Nitric oxide generated by the lining of the vessel is known to relax, and to protect, arteries and veins."

The researchers found PPIs led to an approximately 25 percent increase in ADMA in mouse and tissue cultures, and reduced the ability of mouse blood vessels to relax by over 30 percent on average.

Acid reflux drug may cause heart disease, study suggests

Phase III trial shows afatinib offers clinical benefit to patients with EGFR mutation positive NSCLC

We know that, Afatinib (INN; trade name Gilotrif, previously Tomtovok and Tovok) is an approved drug against non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim As of July 2012, it is undergoing Phase III clinical trials for this indication and breast cancer, as well asPhase II trials for prostate and head and neck cancer, and a Phase I glioma trial. Afatinib is a first-line treatment

.

In October 2010 a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug. Fall 2010 interim results suggested the drug extendedprogression-free survival threefold compared to placebo, but did not extend overall survival. In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.

Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive breast cancer) were described as promising by the authors, with 19 of 41 patients achieving benefit from afatinib. Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug.

Mechanism of action :: Like lapatinib and neratinib, afatinib is a next generation tyrosine kinase inhibitor (TKI) that irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases. Afatinib is not only active against EGFR mutations targeted by first generation TKIs like erlotinib or gefitinib, but also against those not sensitive to these standard therapies. Because of its additional activity against Her2, it is investigated for breast cancer as well as other EGFR and Her2 driven cancers.

Phase III trial shows afatinib offers clinical benefit to patients with EGFR mutation positive NSCLC

FDA Approves Khedezla for Major Depressive Disorder

We know that, Desvenlafaxine (brand name: Pristiq), also known as O-desmethylvenlafaxine, is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class developed and marketed by Wyeth (now part of Pfizer). Desvenlafaxine is a synthetic form of the major active metabolite of venlafaxine (sold under the brand names Effexor and Efexor). It is being targeted as the first non-hormonal based treatment for menopause. 

Now FDA Approves Khedezla for Major Depressive Disorder