8/8/2012
Researchers Discover New Mechanism Behind Resistance to Cancer Treatment
Developing resistance to chemotherapy is a nearly universal, ultimately lethal consequence for cancer patients with solid tumors – such as those of the breast, prostate, lung, and colon – that have metastasized throughout the body. A team of scientists led by
“Cancer cells inside the body live in a very complex environment or neighborhood. Where the tumor cell resides and who its neighbors are influence its response and resistance to therapy,” said Senior Author Peter S. Nelson, MD, a member of the
Dr. Nelson and colleagues found that a type of normal, noncancerous cell that lives in cancer’s neighborhood – the fibroblast – when exposed to chemotherapy sustains DNA damage that drives the production of a broad spectrum of growth factors that stimulate cancer growth. Under normal circumstances, fibroblasts help maintain the structural integrity of connective tissue, and they play a critical role in wound healing and collagen production.
Specifically, the researchers found that DNA-damaging cancer treatment coaxes fibroblasts to crank out a protein called WNT16B within the tumor microenvironment, and that high levels of this protein enable cancer cells to grow, invade surrounding tissue, and resist chemotherapy.
The researchers observed up to 30-fold increases in WNT production – a finding that was “completely unexpected,” said Dr. Nelson. The WNT family of genes and proteins plays an important role in normal development and also in the development of some cancers but, until now, was not known to play a significant role in treatment resistance. This discovery suggests that finding a way to block this treatment response in the tumor microenvironment may improve the effectiveness of therapy.
“Cancer therapies are increasingly evolving to be very specific, targeting key molecular engines that drive the cancer rather than more generic vulnerabilities, such as damaging DNA. Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies. In other words, the same cancer cell, when exposed to different neighborhoods, may have very different responses to treatment,” said Dr. Nelson.
The major clinical reason that chemotherapy ultimately fails in the face of advanced cancer, he added, is because the doses necessary to thoroughly wipe out the cancer would also be lethal to the patient. “In the laboratory we can “˜cure’ most any cancer simply by giving very high doses of toxic therapies to cancer cells in a petri dish. However, in people, these high doses would not only kill the cancer cells but also normal cells and the host.”
Therefore, treatments for common solid tumors are given in smaller doses and in cycles, or intervals, to allow the normal cells to recover. This approach may not eradicate all of the tumor cells, and those that survive can evolve to become resistant to subsequent rounds of anti-cancer therapy.
For the study the team of researchers, which also involved investigators at the University of Washington, Oregon Health and
“This study is an example of collaborative, translational research that capitalizes on years of federally funded investments into the development of tissue banks and clinical trials in which we were able to track long-term patient outcomes. Investing in this type of infrastructure is critical but may take many years to see payoff,” said Dr. Nelson, who serves as Principal Investigator of the Pacific Northwest Prostate Cancer SPORE, a federally funded, multi-institution research consortium led by the
The National Institutes of Health, the National Cancer Institute, the Department of Defense and the Prostate Cancer Foundation funded the research.
CoreRx, Inc. Opens State-of-the-Art Facility
CoreRx, Inc. recently announced it is now occupying its new 35,000-sq-ft facility in
The new complex will encompass nearly four times the former site and will more than triple per day production capacity, reinforcing CoreRx’s status as a leader in the pharmaceutical contract development and manufacturing industry. Enhancements are continually made to its already strong record of providing the most outstanding customer service in the business while helping customer-partners grow their share of the pharmaceutical industry.
CoreRx’s new plant is a high-capacity Good Manufacturing Practices (GMP) certified facility equipped with the latest Trane catalytic air cleaning system and climate-control systems for temperature, humidity, and air quality. The analytical laboratories, outfitted with the latest scientific instrumentation, ensure that all products are tested and released to the highest standards of quality.
The flexible facility together with CoreRx’s cross-trained, multi-skilled work force ensures fast processing times, high-tech manufacturing capability, extensive excipient and packaging component inventory, superior customer service, and overall cost control. CoreRx’s expanded new facility allows them to quickly and efficiently transform their customer’s concepts into reality and manufacture products in order to shorten client’s time to the clinic and ultimately to the commercial marketplace. Fully appreciating that time-to-market is critical, CoreRx offers remarkably flexible, affordable, and rapid outsourcing services designed to meet clients’ specific development and manufacturing needs. CoreRx’s clients represent both small and large companies, within the pharmaceutical and biotechnology industries, and academic institutions who have a focus on clinical studies.
CoreRx is a contract research organization providing customized preformulation services, formulation development, manufacturing, and analytical services to pharmaceutical, biotechnology, academic, and veterinary clients. For more information, visit www.corerxpharma.com.
Aptar’s Dose Indicator Chosen for Allergic Rhinitis
ZETONNA (ciclesonide) Nasal Aerosol from Sunovion Pharmaceuticals Inc., equipped with an Aptar Pharma Landmark® dose indicator, is now available in the
World leader in the development and manufacturing of nasal and pulmonary drug delivery devices, Aptar Pharma worked closely with Sunovion Pharmaceuticals for over 6 years to develop a unique customized Dose Indicator for the delivery of ZETONNA. The innovative actuator offers an alternative to conventional spray pump-based systems.
ZETONNA (ciclesonide) Nasal Aerosol is a corticosteroid indicated for the treatment of symptoms associated with seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older. ZETONNA Nasal Aerosol’s delivery system is a non-aqueous, dry aerosol spray for once daily use, with one spray per nostril. Each canister of ZETONNA Nasal Aerosol contains enough medicine for 60 metered actuations, equivalent to one month of treatment. ZETONNA is currently available in the
Allergic Rhinitis is estimated to affect approximately 60 million people in the
As worldwide leader in nasal spray pumps for allergic rhinitis treatments, Aptar Pharma is continually expanding its portfolio of drug delivery device solutions to the pharmaceutical industry. This portfolio includes a full range of spray pumps, side-actuation systems, dry mist pMDIs as well as dose indicators and mechanical and electronic dose counters.
ZETONNA is a CFC-free Nasal Aerosol formulated with hydrofl uoroalkane (HFA) propellant in a pressurized Metered Dose Inhaler (pMDI), which incorporates Aptar Pharma’s well-known Landmark dose indicator technology. With the help of Aptar Pharma’s R&D team, ZETONNA Nasal Aerosol was customized to include the convenient, built-in Landmark dose indicator actuator. Landmark counts downward and provides the patient with a visual color and numerical reference when it is time to refill the prescription before the container becomes empty.
The Landmark dose-counting mechanism operates independently from the patient’s actuation force. The compact and robust design of Landmark includes a plastic cap to protect the nose tip from dust, which is attached to the Landmark actuator to avoid it being lost. The US FDA recommends that drug manufacturers integrate a dose-counting device into new pMDI drug products.
Aptar Pharma’s Landmark was developed to be compliant with the functional and technical requirements defined by US FDA in their guidelines for dose-counting devices for pMDI products. This patented mechanical dose indicator is easy to use and cost effective. Landmark won an FEA (European Aerosol Federation) international aerosol award in 2007.
“The collaboration between Aptar Pharma and Sunovion is a source of great satisfaction, and we are particularly proud to have developed this customized device for ZETONNA,” said Pierre Carlotti, Vice President Marketing and Communication for Aptar Pharma Prescription Division.
“The launch of ZETONNA Nasal Aerosol in the
Aptar Pharma is part of the Aptargroup family of companies, along with Aptar Beauty + Home and Aptar Food + Beverage. It creates innovative drug delivery systems that meet the evolving needs of biotechnology, healthcare, and pharmaceutical companies around the world. For more information, visit www.aptar.com/pharma.
Advantar Adds Executive Superhero
Advantar Laboratories, Inc. recently announced the addition of Dave Bergstrom, PhD, to the company’s executive team as Chief Operating Officer. Dr. Bergstrom will be responsible for managing overall business operations, including laboratory maintenance, project management, facilities planning, and human resources.
“Dr. Bergstrom brings to our team an invaluable amount of experience in drug development across the commercial and contract sides of our Industry” said Rich Kenley, PhD, CEO of Advantar Laboratories, Inc. “We’re looking forward to his leadership and contributions that will translate to increased customer value and even more efficient laboratory operations, thus strengthening our ability to continue empowering drug development.”
“Advantar has demonstrated strong growth since opening its doors in 2009, and their recent lab expansion is a testament to their overall experience and ability to formulate with the right ingredients for success. I look forward to ensuring we have the right tools, teams, and systems in place that will allow for scaling of existing service offerings and the seamless integration of new ones in the future,” said Dr. Bergstrom.
Dr. Bergstrom comes to Advantar from NovaDel Pharmaceuticals, Inc., where he joined in 2006 as Senior Vice President and Chief Operating Officer. He previously served as Senior Vice President and General Manager of the Pharmaceutical Development business of Cardinal Health, Inc. Prior to Cardinal Health, Dr. Bergstrom served as Vice President of Pharmaceutical and Chemical Development at Guilford Pharmaceuticals and also served in senior positions in preclinical development and pharmaceutical and analytical development at Hoechst-Roussel Pharmaceuticals, Inc., predecessor companies of Sanofi-Aventis Pharmaceuticals, Inc.
San Diego, CA-based Advantar Laboratories, Inc. is a top-tier contract testing laboratory specializing in Routine QC & Monograph Testing, Methods Development/Validation, Pre-formulation, and Formulation Development, QA Consulting, Clinical Packaging/Kitting and ICH Stability Studies for small and large molecule programs ranging in phase from Pre-clinical through to Clinical and Commercial. For more information, visit www.advantarlabs.com or contact Brandon Griffin at (858) 228-7788.
Purac Acquires FiberLive Technology
Purac recently announced it has acquired the FiberLive technology from Vivoxid Ltd.,
FiberLive is a unique composite consisting of resorbable glass fibers and resorbable polymers, forming the strongest fully resorbable material available today. With the acquired technology, Purac Biomaterials will further strengthen its position in the resorbable biomedical market, enabling Purac Biomaterials to develop, manufacture, and market new materials with load bearing properties.
“This technology will be a game changer in the orthopedic resorbable market, where load bearing properties are needed, such as trauma and spine applications,” said Menno Lammers, Managing Director Purac Biomaterials. “The FiberLive technology is the strongest fully resorbable material available for human implants, with strength up to 6 times higher than cortical bone, comparable to metal.”
For more information, visit http://www.purac.com/purac-biomaterials.
InSite Vision Initiates First Phase III Clinical Study
InSite Vision Incorporated recently announced that patient enrollment has begun in the first Phase III clinical trial of BromSite (ISV-303) for the reduction of pain and inflammation after cataract surgery. This study will seek to enroll approximately 240 patients undergoing cataract surgery in a two-arm trial designed to evaluate the efficacy and safety of BromSite against the DuraSite vehicle alone. BromSite combines a low dose (0.075%) of the non-steroidal anti-inflammatory drug (NSAID) bromfenac with InSite Vision’s DuraSite drug delivery technology.
“BromSite has the potential to significantly improve care for patients undergoing cataract surgery in the rapidly growing eye surgery market,” said
The BromSite Phase III clinical study is a two-arm, double-blind, placebo-controlled clinical trial in which the placebo arm will be the DuraSite vehicle. Using 15 separate sites, patients undergoing cataract surgery will be randomized and then dosed twice-a-day beginning the day before surgery and continuing the day of surgery and 14 days post-surgery. The primary study endpoint is the reduction of pain and inflammation after surgery. Pharm-Olam International has been selected to serve as the contract research organization managing the BromSite study on behalf of InSite Vision.
This is the first of two Phase III clinical studies in support of BromSite’s regulatory submissions. In the second quarter of 2012, InSite conducted an end-of-Phase II meeting with the US FDA and two European regulatory meetings, where both BromSite pivotal trials were discussed. The design of the second Phase III study for BromSite will soon be finalized pending full input from both the European regulators and the FDA.
In the Phase I/II study of 169 patients undergoing cataract surgery, once-daily and twice-daily doses of BromSite were compared against the DuraSite vehicle alone. Once-a-day BromSite was demonstrated to be superior to vehicle (53.3% versus 19%, P-value of 0.0016) in reducing pain and inflammation. InSite reported results from the Phase I/II clinical study in March 2011.
In a Phase II clinical study evaluating pharmacokinetics, BromSite achieved more than twice the eye tissue penetration than Bromday (bronfenac ophthalmic solution) 0.09% marketed by ISTA Pharmaceuticals. Results from the Phase II clinical trial comparing BromSite to Bromday were released in October 2011.
Cataract surgery is the most frequently performed ocular surgery in the
InSite’s DuraSite sustained delivery technology is a synthetic polymer-based formulation designed to extend the residence time of a drug relative to conventional topical therapies. It enables topical delivery of a solution, gel, or suspension and can be customized for delivering a wide variety of potential drug candidates. The DuraSite platform is currently leveraged in two commercial products for the treatment of bacterial eye infections, AzaSite and Besivance. InSite Vision is advancing a portfolio of novel preclinical-to-clinical-stage ophthalmic products based on the DuraSite platform.
InSite Vision is advancing new ophthalmologic products for unmet eye care needs. The company’s product portfolio utilizes InSite Vision’s proven DuraSite bioadhesive polymer core technology, an innovative platform that extends the duration of drug retention on the surface of the eye, thereby reducing frequency of treatment and improving the efficacy of topically delivered drugs. For more information, visit www.insitevision.com.
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