STATINS: CHOLESTEROL-LOWERING DRUG BOOSTS BONE REPAIR
Lovastatin, a drug used to lower cholesterol and help prevent cardiovascular disease, has been shown to improve bone healing in an animal model of neurofibromatosis type 1, according to researchers at Max Planck Institute for Molecular Genetics, Berlin. The findings, reported in the open access journal BMC Medicine, showed that lovastatin appears to accelerate cortical bone repair primarily by enhancing new bone formation within the bone marrow cavity and by replacing fibro-cartilaginous tissue in the injury site with mineralized bone matrix in mice. The researchers said the results suggest the usefulness of lovastatin in the treatment of neurofibromatosis-related fracture healing abnormalities.

 

Thousand Oaks, California-based Amgen said a phase 3 trial demonstrated that its denosumab treatment for postmenopausal osteoporosis both increased bone mass and reduced the risk of skeletal fractures in women. Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, an essential regulator of osteoclasts (the cells that break down bone). In this three-year, international study of about 7,800 women with osteoporosis, patients were randomized to receive either denosumab, given by subcutaneous injection once every six months, or placebo injections. For the primary endpoint, treatment with denosumab resulted in a statistically significant reduction in the incidence of new vertebral fractures compared with placebo treatment, the company said. In addition, women receiving denosumab experienced a statistically significant reduction in the incidence of new non-vertebral and hip fractures (each secondary endpoints) compared with those receiving placebo, the company added. The incidence and types of both adverse and serious adverse events observed in this study, including serious infections and neoplasms, were similar between the denosumab and placebo groups, Amgen said. The most common adverse events across both treatment arms were arthralgia, back pain, hypertension, and nasopharyngitis.

 

LIVER CANCER: NEXAVAR APPROVED FOR TREATMENT IN CHINA

Wayne, New Jersey-based Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals of Emeryville, California said the State Food and Drug Administration of China has approved Nexavar (sorafenib) tablets for the treatment of patients with unresectable or metastatic hepatocellular carcinoma or liver cancer. Nexavar is the first and only oral targeted therapy to significantly improve overall survival in patients with the disease the companies said. The approval was based on two international Phase 3 double-blind, placebo-controlled trials that evaluated more than 800 patients who received no prior systemic therapy, they added. China has the highest number of liver cancer patients worldwide, with more than 340,000 new cases diagnosed each year, said Bayer HealthCare. Hepatocellular carcinoma is the most common form of liver cancer and is responsible for about 90 percent of the primary malignant liver tumors in adults, the companies said. Nexavar targets both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply), which are two important processes that enable cancer growth, the companies said.

 

South San Francisco-based Exelixis said it told GlaxoSmithKline it has achieved proof-of-concept for its small molecule anticancer compound XL184 under the collaboration agreement between GSK and Exelixis. Under the agreement, GSK has 90 days to review the data and decide whether to exercise its option to select the compound for further development and commercialization, the company said. If GSK selects XL184, Exelixis would receive a $55-million milestone creditable by GSK against outstanding amounts under the loan facility between the parties, and potentially would receive commercialization milestones, royalties on product sales, and certain co-promotion rights in North America. Exelixis anticipates a decision from GSK by late October 2008. Exelixis said it believes that XL184 shows great potential as a new therapy for patients with medullary thyroid cancer for which no standard of care is currently available. XL184 targets the MET, RET, and VEGFR2 receptor tyrosine kinases.

 

ANGINA: FDA CONTINUES TO REVIEW RANEXA APPLICATIONS BEYOND PDUFA DATE

Palo Alto, California-based CV Therapeutics said it has been informed by the U.S. Food and Drug Administration that it is continuing its review of CV Therapeutics pending applications for Ranexa (ranolazine extended-release tablets) for first-line treatment of angina past the Prescription Drug User Fee Act action date of July 27. Ranexa is currently indicated for the treatment of chronic angina in patients who have not achieved an adequate response with other antianginal drugs. The applications seek a first-line angina indication and promotable claims for the reduction of hemoglobin A1c (HbA1c) and ventricular arrhythmias in patients with coronary artery disease, the company said. The FDA has informed the company that it should receive draft labeling in the next few weeks. In September, the company said it had submitted a supplemental new drug application to the FDA seeking an expansion of the approved product labeling for Ranexa for the new indication and a significant reduction in cautionary language, based on substantial data from the MERLIN TIMI-36 study.

 

Redwood City, California-based Genelabs Technologies said it is in a research pact with the Taiwan’s National Health Research Institutes and Genovate to jointly conduct further research to discover and develop compounds that target the hepatitis C virus. NHRI and Genelabs scientists will jointly work to discover and develop new HCV drug candidates by utilizing Genelabs’ know-how and lead compounds on an existing target and NHRI’s chemistry and drug discovery expertise, the company said. The collaboration will increase the level of chemistry and biology research activities on a selected Genelabs project targeting the HCV virus, the company added.

 

RESEARCH TOOLS: SCIENTIST DEVELOP MICROSCOPIC MICROSCOPE
Researchers at the California Institute of Technology have developed a super-compact high-resolution microscope, small enough to fit on a finger tip. This “microscopic microscope” operates without lenses, but has the magnifying power of a top-quality optical microscope. It can be used in the field to analyze blood samples for malaria or check water supplies for giardia and other pathogens, and can be mass-produced for around $10. Dubbed an optofluidic microscope, the new instrument combines traditional computer-chip technology with microfluidics—the channeling of fluid flow at incredibly small scales. An entire optofluidic microscope chip is about the size of a quarter, although the part of the device that images objects is only the size of Washington’s nose on that quarter.

 

Researchers at the Stanford University School of Medicine have found that mature, specialized cells naturally regress to serve as a kind of de facto stem cell during the fruit-fly life cycle. The findings, published in Science Express, counter the common belief that the ability to form new cell types or tissues wanes as a cell becomes more specialized. Harnessing this type of developmental backtracking in adult human cells would allow researchers to explore new avenues for treating many human diseases. Although recent research has shown that human skin cells can be coaxed in a laboratory dish to generate many other types of cells, the conversion requires the use of viruses to deliver specific combinations of genes into the cells. The existence in humans of similar, naturally occurring stem cell understudies, called “facultative stem cells,” has recently been proposed, but the idea remains controversial.

               

San Carlos, California-based Nuvelo said that it has enrolled the first subject in a single-center, early-stage trial of recombinant, secreted protein, NU206, the company’s lead compound from its Wnt Therapeutics Program. This double-blind, placebo-controlled, single-ascending dose trial will determine the safety, tolerance and pharmacokinetics of a single intravenous administration of NU206, in approximately 48 healthy male volunteers. Participants will be enrolled in up to six cohorts of varying doses. Due to its ability to promote cell growth and repair in preclinical studies, the company believes that NU206 has the potential to offer a novel approach for the treatment of serious medical conditions including gastrointestinal injury, inflammatory bowel disease, and bone disease. NU206 is a recombinant, secreted protein that acts as a key regulator of the Wnt pathway, the critical pathway that stimulates cell growth and differentiation during homeostasis and pathogenesis in specific tissues including the GI epithelium and bone. Preclinical studies suggest it can promote growth and repair in animal models of radiation or cancer chemotherapy induced GI injury, inflammatory bowel disease, bone disease and wound healing.

 

DRUG DEVELOPMENT: SINGULEX GETS SECOND PHASE SBIR GRANT FROM NCI TO DEVELOP BIOMARKER ASSAYS
Alameda, California-based Singulex said it secured the second phase of its Fast Track Small Business Innovation Research contract from the National Cancer Institute. The company will use the funds to develop biomarker assays that will be useful in determining whether a potential cancer therapeutic is effective. Because the levels of specific proteins vary depending on disease state, biomarkers, or proteins associated with a disease, can be measured to determine whether a disease is progressing. In addition, by measuring changes to disease-associated biomarkers following treatment with a specific drug, pharmaceutical developers can assess whether a drug candidate demonstrates efficacy. Singulex said the problem has been that technologies have not existed that allow detection sensitively enough to see the subtle changes that enable drug developers or clinicians to use biomarkers to assist in the development of medicines or to make clinical decisions. The company has developed an assay to detect VEGF, a protein implicated in many cancers, that it says overcomes the limitations of traditional biomarker detection technologies and allows drug developers to see normal levels of VEGF in blood and assess the efficacy of anti-VEGF drugs. The development of the VEGF assay was supported with Phase I of the Fast Track SBIR contract. Singulex said the Phase II grant will provide it with the resources to develop 12 more assays to different biomarkers that will provide insights into drug efficacy in additional oncology areas.

 

ARTHRITIS: FRANKINCENSE PROVIDES RELIEF TO SUFFERERS
An enriched extract of the Indian Frankincense herb Boswellia serrata has been proven to reduce the symptoms of osteoarthritis, according to researchers at the University of California, Davis. Research published today in the open access journal Arthritis Research & Therapy has shown that patients taking the herbal remedy showed significant improvement in as little as seven days. Osteoarthritis is the most common form of arthritis; it commonly affects weight-bearing joints such as the knees and hips, along with the hands, wrists, feet and spine. The symptoms include pain, stiffness, and limited movement. This randomized, double-blinded, placebo-controlled trial of 70 patients will be of great interest to sufferers, especially those who don’t get adequate relief from existing treatments. The high incidence of adverse affects associated with currently available medications has created great interest in the search for an effective and safe alternative treatment, the researchers said. The extract the researchers used was enriched with 30 percent AKBA (3-O-acetyl-11-keto-beta-boswellic acid), which is thought to be the most active ingredient in the plant. AKBA has anti-inflammatory properties. This is a proprietary product developed by Laila Nutraceuticals.