Gilead Sciences Truvada

Gilead Sciences has submitted an sNDA application for the approval of once-daily Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP) to reduce the risk of HIV-1 infection among uninfected adults. Truvada was approved by the FDA in 2004 for the treatment of HIV-1 infection and is currently the most-prescribed antiretroviral treatment in the US.

If the sNDA is approved, Truvada would be the first agent indicated for uninfected individuals to reduce the risk of acquiring HIV through sex, a prevention approach called PrEP. The application is based on the results of two large placebo-controlled trials of Truvada as PrEP, sponsored by the National Institutes of Health (NIH) and the University of Washington.

The first trial providing data to support the Truvada sNDA is a Phase III, randomised, double-blind, placebo-controlled trial known as the Pre-Exposure Prophylaxis Initiative (iPrEx), which was sponsored by the NIH and conducted among 2,499 high-risk HIV-negative adult homosexuals in the US and countries in Africa, Asia and South America. Results from the trial, published in the New England Journal of Medicine in November 2010, showed that once-daily use of Truvada for PrEP reduced the risk of acquiring HIV overall by 44 per cent compared with placebo and by up to 73 per cent among men who reported taking the drug consistently (defined as at least 90 per cent of days). Among men who took the drug consistently enough to have detectable drug in their body, the risk was reduced by more than 90 per cent.

The Truvada sNDA submission is also supported by data from Partners PrEP, a Phase III, randomised, double-blind, placebo-controlled trial conducted among 4,758 heterosexual couples in Kenya and Uganda, in which one partner was infected with HIV and the other was not. The trial, sponsored by the University of Washington, showed that once-daily use of oral Truvada by the HIV-negative participants reduced their risk of acquiring HIV by 73 per cent compared with placebo.

Additional supportive data come from two studies sponsored by the Centers for Disease Control (CDC). The first trial, known as TDF2, was a Phase III, randomised, double-blind, placebo-controlled trial conducted in Botswana among 1,200 HIV-negative heterosexual men and women. Participants taking once-daily oral Truvada for PrEP had 63 per cent fewer HIV infections compared with those receiving placebo. The second trial, known as CDC 4323, was a Phase II, randomised, placebo-controlled, double-blind study of homosexual men in the US primarily designed to assess the safety, adherence and acceptability of PrEP.

Although full details are not yet available, another separate Phase III study of Truvada for PrEP known as FEM-PrEP was stopped in April 2011 based on a recommendation by the study’s Independent Data Monitoring Committee that the trial would not be able to establish the efficacy of Truvada among HIV-negative women in sub-Saharan Africa. The reason for this outcome is not yet understood and a complete detailed analysis of the data is currently under way.

In all studies, side-effects included nausea, weight loss and serum creatinine elevations. The incidence of side effects was consistent with Truvada’s safety and tolerability profile when used as HIV treatment, which is supported by more than 1.8 million years of patient use. Overall, there have been more than 4.4 million patient years of experience with tenofovir-containing regimens. Three cases of resistance to emtricitabine were reported in the iPrEx trial among participants who tested negative for HIV infection by serology at enrollment, but were later found to have been infected with HIV prior to enrolment using a different assay. Two of these cases occurred in the active drug arm, and one case occurred in the placebo arm.

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Ambulatory blood pressure may “best predict brain disease and cognitive decline”

Ambulatory blood pressure – not the doctor’s office blood pressure – can best predict the progression of small vessel brain disease and the decline of cognitive function in older people, according to a new study in Circulation: Journal of the American Heart Association. Ambulatory blood pressure is measured by monitoring blood pressure at regular intervals using a special recording device under normal living and working conditions. Clinical or in-office blood pressure is taken in a healthcare provider’s office. The National Institutes of Health funded the study.

According to Dr William B White, senior author of the study and professor of hypertension and clinical pharmacology in the Calhoun Cardiology Center at the University of Connecticut School of Medicine in Farmington, the study showed for the first time in an older population that blood pressure measured over a 24-hour period was associated with the progression of vascular brain disease, whereas the typical office blood pressure was not. To determine the effect blood pressure had on the progression of brain disease, researchers examined the change in blood pressure and volume of white matter hyperintensities (WMH) in the brain at baseline and after two years.

WMH are a sign of small vessel brain damage that can be detected using an MRI. In addition to looking for WMH, researchers measured cognitive ability and physical mobility over the two-year time period. Previous studies by the authors and other researchers have shown that increased WMH is associated with cognitive decline. A worsening in ambulatory blood pressure was associated with an increase in WMH and a decrease in cognitive and mobility functions. If medical professionals target average ambulatory blood pressure, it could reduce the progression of small vessel brain disease, researchers stated.

The two-year study included 72 patients – average age 82. For the group, there were no major changes in body weight, clinical or ambulatory blood pressure during the study, and only three patients had severe medical problems, including the development of stroke, heart failure or valvular disease. Researchers found no relationship between clinical blood pressure and WMH; the average volume of WMH, when adjusted for age and “bad” LDL cholesterol, increased significantly over two years from 13.9mL to 20.5mL; and three of the four mobility measures and all of the cognitive measures were significantly related to WMH volume at two years.

The results of this cohort study mean that for older people who aim to stay as functional as possible during advancing age, their blood pressure averaged out of the office, rather than in the office, might be the most important to target and treat.

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Welcome back to The Medical Technology Blog, todays article is taken from Espicom’s business publication Diagnostics Focus, please read on…

Johns Hopkins University (JHU) scientists have developed a gene-based test to distinguish harmless from precancerous pancreatic cysts, and which could eventually help some patients avoid needless surgery to remove the harmless variety. The investigators estimate that fluid-filled cysts are identified in more than a million patients each year, most of whom have undergone CT or MRI scans to evaluate non-specific symptoms, such as abdominal pain and swelling.

Dr Bert Vogelstein, co-director of the Ludwig Center at JHU and a Howard Hughes Medical Institute investigator, and his colleagues analysed precancerous cysts from 19 patients and searched for mutations in 169 cancer-causing genes. They found mutations in the KRAS gene, known for its prevalence in pancreatic cancers, and the GNAS gene, which had not previously been associated with pancreatic cancer. In both KRAS and GNAS, the mutations occur at a single coding spot in the DNA, the equivalent of a typo in a word within an entire encyclopaedia. KRAS and GNAS genes produce signalling proteins, relaying signals from the cell surface to areas within the cell.

The researchers then tested a total of 132 precancerous pancreatic cysts for mutations in KRAS and GNAS. The latter were found in more than half of the samples (87 of them), and KRAS mutations occurred in 107 samples. Nearly all (127) had mutations in GNAS, KRAS or both. The mutations occurred in large and small, high- and low-grade cysts, and in all major types of the most common precancerous pancreatic cysts. There were no major differences in age, gender or smoking history for people with GNAS or KRAS mutations in their cysts’ cells. Finally, the investigators tested tissue from pancreatic cancers that had developed in eight people with GNAS-mutated cysts. Seven of the eight had GNAS mutations in their cancer, as well as cells in the cysts.

GNAS and KRAS mutations were not found in benign cysts, although KRAS mutations did appear occasionally in a rare type of cyst with a relatively low potential to become cancerous. These rare, mostly benign cysts are less challenging to diagnose because of their location within the pancreas and type of patient, according to the investigators. Genetic analysis of the kind reported in the new study offers a new way to sort the potential of these cysts to cause malignant trouble.

The investigators caution that cyst fluid removal, an invasive procedure, also has its drawbacks and can cause bleeding, infection and inflammation in a very small percentage of patients. Further studies on a larger number of patients are expected to be done before the gene-based test can be widely offered. However, Vogelstein says that the technology for developing a gene-based test in this case is relatively straightforward because “the mutation occurs at one spot in both of the genes.”

Major funding for the study was provided by the Lustgarten Foundation, a private foundation that provides to funding pancreatic cancer research. Other funding was provided by the Virginia and D K Ludwig Fund for Cancer Research, the Sol Goldman Center for Pancreatic Cancer Research, the Joseph L Rabinowitz Fund, the Michael Rolfe Foundation, the Indiana Genomics Initiative of Indiana University, which is supported in part by Lilly Endowment., the J.C. Monastra Foundation, Swim Across America and the National Institutes of Health. JHU has filed a patent application on inventions described in the study.

Thanks to Lawrence Miller for this post, if you woul like more information like this, or to start your subscription please click on the link  Diagnostics Focus Newsletter

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Nuvilex, a company that dedicates itself to the development of natural and biotechnology products, has made the canny decision to up sticks and move its corporate headquarters from Scottsdale, AZ, to Silver Spring, MD – only four miles from the FDA’s doorstep. Nuvilex is hoping that the move – which is in its final stages – will give the company immediate access to the FDA’s resources as the company pursues clinical development of its pancreatic cancer treatment technology, as well as other biotechnology developments in the future.

Not only is the company’s HQ in the FDA’s backyard, it is also only about ten miles away from the National Institutes of Health, and the National Cancer Institute – both major sources of funding grants and research collaborations. To explain the move, Nuvilex’ President and CEO, Dr Robert F Ryan, said the new location “..will facilitate our interactions with the FDA, an important part of our overall strategic planning, especially given our recent entry into biotechnology and our plans for expansion in this area”.

Nuvilex’ pancreatic cancer treatment is currently being geared-up for more clinical trials, and apparently, significant advances are in progress with the company’s live-cell encapsulation technology. Natural products in development include Gluten-Free Cinnergen and others to enhance a healthy lifestyle. The company is also developing products designed for cosmetic use, flu treatment and the use of heavy-metal-free tattoo inks. Future developments are planned for Citroxin and Oraphyte, Nuvilex’ antimicrobial and antinematodal agents.

This article was kindly provided by Sophie Bracken, editor of Drug Delivery Insight for Espicom.

Kensey Nash finds way in to regenerative medicine market through Nerites takeover

Kensey Nash, a company focused on regenerative medicine via its collagen and synthetic polymer technologies, has snapped up Nerites, a Madison, WI-based developer of metal adhesives and anti-fouling coatings. The purchase was made for US$20 million in cash.

Right now, Nerites is developing a platform for adhesive-based biomaterials that Kensey Nash thinks would help it enter the regenerative medicine market, which covers soft tissue repair, orthopaedics, sports medicine, spine and neurosurgery. Surgical sealants can be used in most procedures, and over the past few years the wound closure market has moved from staples and sutures to a new generation of technologies, including a range of external and internal surgical adhesives. These products compete in a market that serves over 70 million surgical wounds in the US alone. The market is estimated to be worth over US$1 billion by 2015.

As well as new surgical sealants and adhesives, Kensey Nash says it wants to develop and integrate the acquired adhesive, sealant and coating technologies into its Regenerative Biomaterials business. The firm believes that through this technology it can develop a portfolio of next-generation hybrid adhesive-based products that integrate its ECM, collagen and polymer technologies for use in general, neurologic, plastic/reconstructive, orthopaedic, urologic, cardiovascular and thoracic surgical specialties. The company first intends to develop products for repairing defects in abdominal walls, dural membranes and gastro-intestinal tracts.

Kensey Nash also wants to look at applications for the Nerites anti-fouling technology for preventing bacterial biofilm formation. Biofilms form when micro-organisms attach to implanted medical devices, and form a biological film coating that can interrupt healing, and cause infection. It is thought hat device-related biofilm infections can increase hospital stays and add over US$1 billion per year to US hospitalisation costs.

According to Nerites, its technology is inspired by proteins secreted by marine mussels for bonding to underwater surfaces. Research carried out on these adhesive proteins by Dr Phillip Messersmith of Northwestern University identified a key compound believed to be primarily responsible for the adhesive properties. Synthetic versions of these components have been developed to create biomaterials capable of binding to tissue and other materials in aqueous surgical environments. Nerites has funded the activities through US$11 million from venture capital and private investors, as well as an additional US$5 million in NIH and NSF SBIR grants.

Though the loose ends of the transaction have not yet been tied up, Kensey Nash thinks the purchase will be dilutive to earnings by around US$0.02 per share in the second half of 2011, and expects that in 2012, it will have a neutral impact on earnings, as any R&D spending on the Nerites technology will be reallocated from other projects.

Thanks to Sophie Bracken for this article, Sophie is  the editor for Orthopaedic Business News