Friday, March 6, 2015

Ganciclovir drug resistance may occur more frequently in cystic fibrosis patients



Ganciclovir structure.svg




A drug called ganciclovir is given to lung transplant patients to protect against a life-threatening virus that is common after transplantation.
Ganciclovir reduces mortality due to the virus from 34 percent to between 3 and 6 percent. But between 5 percent and 10 percent of patients infected with the virus have strains that are resistant to the drug.
A Loyola University Medical Center study found that such resistance may occur more frequently in cystic fibrosis patients. These patients were found to have insufficient levels of the drug in their bloodstream, enabling the virus to continually replicate. This in turn may increase the chance that mutations will occur and result in drug resistance.
The study suggests that cystic fibrosis patients should be monitored to ensure there are therapeutic levels of ganciclovir in their bodies, said James Gagermeier, MD, first author of the study. The study is published online ahead of print in the journal Transplant Infectious Disease.



Thursday, March 5, 2015

Palatin begins bremelanotide phase 3 study for treatment of female sexual dysfunction



Bremelanotide chemical structure.png


Palatin Technologies, Inc. (NYSE MKT: PTN), a biopharmaceutical company developing targeted, receptor-specific peptide therapeutics for the treatment of diseases with significant unmet medical needs and commercial potential, today announced that it has started its bremelanotide pivotal registration program. The Company has initiated its phase 3 reconnect study in the United States for the treatment of female sexual dysfunction (FSD).

"We are pleased to achieve this major milestone in the bremelanotide program with the initiation of our phase 3 reconnect study in the U.S," stated Carl Spana, Ph.D., President and CEO of Palatin. "This is a key step in our global strategy to bring bremelanotide to market for the millions of women who have FSD and are seeking a safe and effective treatment." Dr. Spana further stated that, "Our recent $30 million financing has provided the financial resources to start the bremelanotide phase 3 pivotal registration program and timing flexibility regarding partnering for the U.S. and other non-European territories."

Wednesday, March 4, 2015

Can-Fite BioPharma begins dosing in CF102 Phase II liver cancer trial



CF-102 structure

Can-Fite BioPharma Ltd. , a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer and inflammatory diseases, today announced that it has dosed the first patient in a Phase II trial for the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer.

The Phase II randomized, double-blind, placebo controlled trial is to be conducted in the U.S., Europe and Israel with an estimated 78 patients to be enrolled. CF 102 is being evaluated for efficacy and safety as a second-line treatment for advanced HCC in subjects with Child-Pugh B who failed Nexavar as a first line treatment. The first patient was dosed at the study's Israeli site, the Rabin Medical Center. The primary endpoint of the study is overall patient survival.

Tuesday, March 3, 2015

Intriguing small molecule directs activity of key ‘clock proteins’

In research published in Nature Communications, Thomas Burris, Ph.D., chair of pharmacological and physiological science at Saint Louis University, reports intriguing findings about a small molecule that directs the activity of key "clock proteins," offering the potential to manage circadian rhythm and treat problems that are associated with its dysfunction, like sleep and anxiety disorders.

 



Circadian rhythm refers to biological processes that cycle every 24 hours. In mammals, the internal clock that maintains circadian rhythm is essential for normal physiological functions. The rhythms can, however, be disrupted, and dysregulation of circadian rhythm is associated with many disorders, including metabolic disease and neuropsychiatric disorders including bipolar disorder, anxiety, depression, schizophrenia and sleep disorders.
Burris and his colleagues examined compounds that target a protein called REV-ERB, which appears to play a key role in regulating mammals' internal clocks.

"It has been suggested that REV-ERB is a core component of our clock," said Burris. "Mice without it are arrhythmic. This study demonstrated that when we give mice a synthetic compound that turns REV-ERB on, it altered their circadian rhythm."
The team examined effects of the REV-ERB drug on patterns of sleep and wakefulness and found that the compound increases wakefulness, reduces REM and slow-wave sleep, and, notably, decreases anxiety.
This is an interesting finding because it is unusual. Frequently, drugs that increase arousal (wakefulness) also increase anxiety (ex. cocaine, amphetamines). And, vice versa: Drugs that decrease anxiety also decrease arousal (ex. benzodiazepines and ethanol). An exception to this common pattern is nicotine.

Monday, March 2, 2015

Actavis receives complete response letter for nebivolol/valsartan FDC for treatment of hypertension

In continuation of my  update on Valsartan

Actavis plc , confirmed that the Company has received a complete response letter from the U.S. Food and Drug Administration (FDA) for its New Drug Application (NDA) for the fixed-dose combination (FDC) of nebivolol (below structure)  and valsartan for the treatment of hypertension.

Nebivolol.svg


"Although we are disappointed in the receipt of a complete response letter, Actavis remains committed to bringing treatments to market that address the significant public health issue of cardiovascular disease," said David Nicholson, Senior Vice President, Actavis Global Brands R&D. "Bystolic is a safe and effective option that is commonly used in combination with other antihypertensive medications to help patients reach blood pressure treatment goals. We will review the complete response and determine the appropriate next steps."


Friday, February 27, 2015

Mirati begins dosage in MGCD265 Phase 1b clinical trial for NSCLC

Mirati Therapeutics, Inc. (NASDAQ: MRTX) today announced that the first patient with Non-Small Cell Lung Cancer (NSCLC) has been dosed in a Phase 1b clinical trial of MGCD265 in selected patients exhibiting genetic alterations of MET or Axl. In this segment of the study, one of the expansion cohorts will enroll patients with NSCLC and another will enroll patients with other solid tumors. Both cohorts will enroll only those patients that have specific MET driver mutations including MET gene point mutations, gene amplification, and MET or Axl gene rearrangements.

MGCD-265 Chemical Structure
"In the dose escalation phase of this trial, we identified an optimal dose that achieved serum levels that we believe will result in greater than 90% inhibition of MET and Axl," said Charles M. Baum, M.D., Ph.D., president and CEO of Mirati. "We are focused on patients whose tumors harbor the specific MET and Axl genetic alterations that MGCD265 is designed to treat. By selecting and treating only those patients who carry the targeted mutations, there is strong rationale that we'll see proof of concept based on a high overall response rate in early 2015 that supports accelerated drug development."

Wednesday, February 25, 2015

Pre-clinical studies confirm TRXE-009 as new potential treatment for melanoma

Novogen Limited (ASX:NRT; NASDAQ: NVGN), Australian/US biotechnology company, announces that it has confirmed that its lead candidate product, TRXE-009, originally developed for the treatment of brain cancers, has been shown in pre-clinical studies also to be highly active against melanoma.

The Company believes this is an important breakthrough discovery for two reasons. The first is that it confirms that TRXE-009 is an important new potential treatment for melanoma, including for the treatment of secondary brain cancers due to melanoma, for which there currently are no effective therapies. The second is that it offers evidence for the first time of an hypothesized link between brain cancer and melanoma.

The link has long been considered a possibility because nerve cells and melanocytes (the melanin pigment-bearing cells in skin that lead to melanoma) have a common origin in the embryo known as the neural crest. This primitive tissue gives rise to the neural cells that go on to form the brain, spinal cord, and peripheral nerves, as well as cells that form the structures of the skull; melanocytes also come from this embryonic tissue. Up till now, no functional link has been found between brain cells and melanocytes, or between brain cancer and melanoma. TRXE-009 is the first compound to demonstrate the possibility of a common link, suggesting that is the first drug with the ability to identify cancers arising in cells that have the neural crest as their common origin.

Monday, February 23, 2015

Isis Pharmaceuticals begins ISIS-DMPK Rx clinical study in DM1 patients

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced  that it has initiated a study for ISIS-DMPKRx in patients with Myotonic Dystrophy Type 1 (DM1). DM1 is a rare genetic neuromuscular disease caused by the production of toxic dystrophia myotonica-protein kinase (DMPK) RNA in cells. ISIS-DMPKRx is specifically designed to reduce toxic DMPK RNA.

"The Myotonic Dystrophy Foundation is pleased that Isis is advancing to the next phase of clinical trials for ISIS-DMPKRx," said Molly White, executive director of the Myotonic Dystrophy Foundation. "Myotonic Dystrophy, the most common form of muscular dystrophy, is a devastating disease with no therapeutic option. Myotonic dystrophy research has accelerated significantly in the last 10 years, helping bring about the innovative science behind ISIS-DMPKRx, a drug that specifically targets the genetic defect that causes myotonic dystrophy type 1. We applaud Isis for investing in and leading drug development efforts for myotonic dystrophy type 1, and we appreciate the commitment Isis Pharmaceuticals has made to improve the lives of patients in our community."

"We have an innovative and productive partnership with Biogen Idec in developing drugs to treat severe and rare diseases, like DM1. In just under two and a half years, we have been able to discover and complete early development on ISIS-DMPKRx, which includes completing a Phase 1 single ascending-dose study in healthy volunteers. Today we advance this program into patients," said B. Lynne Parshall, chief operating officer at Isis. "The speed at which we have advanced ISIS-DMPKRx highlights the productive and collaborative nature of our partnership."

Friday, February 20, 2015

Researchers identify 53 existing drugs that may block Ebola virus from entering human cells



Researchers found 53 existing drugs that may keep the Ebola virus from entering human cells, a key step in the process of infection, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and the National Institutes of Health (NIH), and published today in the Nature Press journal Emerging Microbes and Infections.

Among the better known drug types shown to hinder infection by an Ebola virus model: several cancer drugs, antihistamines and antibiotics. Among the most effective at keeping the virus out of human cells were microtubule inhibitors used to treat cancer.

"In light of the historic and devastating outbreak of Ebola virus disease, there is an urgent need to rapidly develop useful treatments against Ebola infection, and our study results argue that repurposing existing drugs may be among the fastest ways to achieve this," said lead author Adolfo García-Sastre, PhD, Director of the Global Health and Emerging Pathogens Institute within the Icahn School of Medicine at Mount Sinai. "Many of the compounds identified in this study promise to become lead compounds in near-future drug development efforts studies targeting this virus," said Dr. García-Sastre, also the Fishberg Chair and Professor of Medicine (Infectious Diseases) within the School.

A few are listed below...


Ref : http://www.nature.com/emi/journal/v3/n12/full/emi201488a.html

Nocodazole (IC50=0.4 µM), Toremifene (0.55 µM), Tamoxifen (0.76 µM), Raloxifene 1.84 (1.53 µM), Cepharanthine (1.53 µM), Clomiphene (1.72 µM), Dronedarone (2.2 µM), Amodiaquine (4.43 µM), Imipramine (13.7 µM), Chloroquine (15.3 µM), and Nilotinib (15.3 µM).