FDA Supports Phase 3 Trial for NGX-1998 | News | Drug Discovery and Development Magazine

NeurogesX Inc., a specialty pharmaceutical company focused on developing and commercializing a portfolio of novel non-opioid, pain management therapies, provided an update on its regulatory process for NGX-1998 (see below structure), the company's next generation liquid formulation of prescription-strength capsaicin. NeurogesX has received End-of-Phase 2 guidance from the U.S. Food and Drug Administration (FDA) regarding its previously announced plans for the Phase 3 clinical development of NGX-1998 as a treatment for neuropathic pain conditions, including key elements of its overall development plan related to manufacturing, applicator development, and clinical trial design.

FDA Supports Phase 3 Trial for NGX-1998 | News | Drug Discovery and Development Magazine

Less commonly prescribed antibiotic may be better for bloodstream infections

 In continuation of my update on Vancomycin

Kevin Chan, MD (Fresenius Medical Care North America and Massachusetts General Hospital) and his colleagues compared the effectiveness of various antibiotics at preventing hospitalization and death from bloodstream infection. They reviewed more than 500,000 blood culture results from their chronic kidney disease database, looking for methicillin-sensitive strains of S. aureus bloodstream infection. They also identified when physicians used vancomycin or cefazolin to treat these infections. Vancomycin is often perceived as the better antibiotic because it has broad coverage against many strains of bacteria; however, other factors like the antibiotic's killing power and tissue penetration are also important factors in selecting the best treatment.

  

Among the major findings:

• 56% of patients remained on vancomycin after blood culture results reported S. aureus bacteria were susceptible to cefazolin, while only 17% were treated with cefazolin. 
• Cefazolin-treated patients experienced a 38% lower rate of hospitalization and death compared with vancomycin-treated patients. 
• Cefazolin-treated patients also had a 48% lower rate of sepsis, which is the most serious form of bloodstream infection.
• "I think the data suggest there is an opportunity to improve outcomes for patients through appropriate antibiotic selection," said Dr. Chan.

 Less commonly prescribed antibiotic may be better for bloodstream infections

Ref : http://jasn.asnjournals.org/content/early/2012/08/15/ASN.2012010050

Resveratrol might help improve mobility and prevent life-threatening falls among older people

In continuation of my update on Resveratrol...

"Our study suggests that a natural compound like resveratrol, which can be obtained either through dietary supplementation or diet itself, could actually decrease some of the motor deficiencies that are seen in our aging population," said Jane E. Cavanaugh, Ph.D., leader of the research team. "And that would, therefore, increase an aging person's quality of life and decrease their risk of hospitalization due to slips and falls."

Resveratrol might help improve mobility and prevent life-threatening falls among older people

FDA Approves Stivarga | News | Drug Discovery and Development Magazine

In continuation of my update on Stivarga

FDA Approves Stivarga | News | Drug Discovery and Development Magazine

Golden age of prostate cancer treatment hailed as fourth drug in two years extends life

We know that, Enzalutamide (formerly known as MDV3100, see the structure) is an experimental androgen receptor antagonist drug developed by the pharmaceutical company Medication for the treatment of castration-resistant prostate cancer currently in phase 3 clinical trials. Results so far have been encouraging; Medivation has reported up to an 89% decrease in prostate specific antigen serum levels after a month of taking the medicine. Early preclinical studies also suggest that enzalutamide inhibits breast cancer cell growth. 

Researchers from Institute of Cancer Research, London, and its partner hospital The Royal Marsden NHS Foundation Trust jointly led the new Phase III trial of enzalutamide and the Phase III trials of two other drugs, cabazitaxel and abiraterone. Abiraterone was also discovered at The Institute of Cancer Research and was recently made available on the NHS. A further drug sipuleucel-T has also been shown to extend life in the two-year period.

"What we're seeing now is an unprecedented period of success for prostate cancer research, with four new drugs shown to extend life in major clinical trials in just two years, and several others showing promise. It truly is a golden age for prostate cancer drug discovery and development" claims Prof. Martin Gore....

Golden age of prostate cancer treatment hailed as fourth drug in two years extends life

AEOL10150 Protects Against Nerve Gas | News | Drug Discovery and Development Magazine

The study confirmed AEOL10150 (see structure)’s ability to cross the rat blood brain barrier and achieve sufficient levels to exert its neuroprotective effects.  Further, the study showed that subcutaneous administration of AEOL10150 30 min prior to or 60 and 90 minutes after nerve agent exposure resulted in inhibition of markers of oxidative stress and neuronal damage.

“These new data show that AEOL 10150 has potential neuroprotective properties against chemical nerve agents and broaden the utility of protection proved by AEOL 10150 across the chemical threat spectrum”, stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc.  “This study builds on prior work that has shown AEOL 10150 to be an effective countermeasure to protect the lungs from damage due to inhalation of chlorine, sulfur mustard, and phosgene gas and well as protection against radiologic damage to the lungs and gastrointestinal tract.”  

AEOL10150 Protects Against Nerve Gas | News | Drug Discovery and Development Magazine

Pilot Study Drug Controls Blood Sugar in People with HI | The Children's Hospital of Philadelphia

The standard treatment for some forms of congenital HI is diazoxide (right structure), a drug that controls insulin secretion by opening potassium channels in beta cells. However, this drug does not work in the most common types of HI, in which mutations prevent these potassium channels from forming.                                       

A pilot study in adolescents and adults has found that an investigational drug (Exendin 9-39) (see below structure) shows promise as the first potential medical treatment for children with the severest type of congenital hyperinsulinism, a rare but potentially devastating disease in which gene mutations cause insulin levels to become dangerously high.

Pilot Study Drug Controls Blood Sugar in People with HI | The Children's Hospital of Philadelphia

Hint of tafamidis benefit in rare polyneuropathy

The results of a randomized trial suggest that tafamidis treatment may slow the progression of early-stage V30M transthyretin familial amyloid polyneuropathy.

During 18 months of treatment, 45.3% of the 65 patients given tafamidis (see structure) 20 mg/day worsened by less than 2 points on the Neuropathy Impairment Score-Lower Limbs (NIS-LL). The rate among 63 placebo-treated patients was 29.5%, which was a nonsignificant difference. 

The Norfolk Quality of Life-Diabetic Neuropathy total score (TQOL) worsened by 2.0 points in the tafamidis group, compared with 7.2 points in the placebo group - also a nonsignificant difference.

But this analysis was based on the intent-to-treat population. A higher than anticipated dropout rate, caused by patients requiring liver transplantation, meant that just 87 of the original 125 patients actually completed the treatment.

In this group, 60.0% versus 38.1% of those treated with tafamidis and placebo had a less than 2-point deterioration on the NIS-LL, and TQOL scores worsened by a corresponding 0.1 versus 8.9..... 

More...
Hint of tafamidis benefit in rare polyneuropathy

Developing the First Novel Drug Regimen from TB Alliance...

TB Alliance’s push to test new drugs in combination has been done to produce a regimen that not only would be faster and easier for patients, but also would tackle two other challenges as a major step in stopping the spread of drug-resistant TB—the complexity and high cost of treatment. This promising regimen eliminates the use of injectables and projects to reduce the cost of MDR-TB therapy by as much as 90 percent.

The study, NC-001, or New Combination 1, was a two-week trial successfully completed at two centers in South Africa. It involved the new combination therapy called PaMZ, consisting of the novel TB drug candidate, PA-824 (see below structure left); moxifloxacin (right structure), an established antibiotic not yet approved for use in first-line TB therapy and being developed in partnership with Bayer Healthcare AG; and pyrazinamide, an existing TB drug.

“Treating drug-sensitive and drug-resistant TB with the same regimen can simplify the delivery of TB treatment worldwide,” said Andreas Diacon, MD, the trial’s principal investigator and lead author of the Lancet study. “The results of this study give healthcare providers on the front lines of the TB epidemic hope for better, faster tools needed to stop this disease.”

 (Pyrazinamide)

Newscenter | Global Alliance for TB Drug Development

Chemical makes blind mice see; compound holds promise for treating humans

The chemical, called AAQ (see below structure,   acrylamide- azobenzene - quaternary ammonium),  acts   by taking the remaining, normally "blind" cells in the retina  sensitive to  light,  said  lead  researcher  Richard Kramer, UC Berkeley professor of molecular and cell biology.   AAQ is a photoswitch that binds to protein ion channels on the surface of retinal cells. When switched on by light, AAQ alters the flow of ions through the channels and activates these neurons much the way rods and cones are activated by light.

The blind mice in the experiment had genetic mutations that made their rods and cones die within months of birth and inactivated other photopigments in the eye. After injecting very small amounts of AAQ into the eyes of the blind mice, Kramer and his colleagues confirmed that they had restored light sensitivity because the mice's pupils contracted in bright light, and the mice showed light avoidance, a typical rodent behavior impossible without the animals being able to see some light. Kramer is hoping to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.

Because the chemical eventually wears off, it may offer a safer alternative to other experimental approaches for restoring sight, such as gene or stem cell therapies, which permanently change the retina. It is also less invasive than implanting light-sensitive electronic chips in the eye.

"The advantage of this approach is that it is a simple chemical, which means that you can change the dosage, you can use it in combination with other therapies, or you can discontinue the therapy if you don't like the results. As improved chemicals become available, you could offer them to patients. You can't do that when you surgically implant a chip or after you genetically modify somebody," Kramer said...........