BIRMINGHAM, Ala.–(BUSINESS WIRE)–DiscoveryBioMed, Inc. (DBM) today announced that it has been awarded a $750,000 Small Business Innovations Research (SBIR) Phase 2 grant by the National Institutes of Health (NIH) to continue the research into the discovery and development of small molecules to alleviate multiple chronic human diseases including cystic fibrosis (CF), hypertension and chronic kidney diseases with hypertension.
“We are proud to have been awarded this grant and to have our technology again recognized and validated by the NIH,” said Dr. Erik Schwiebert, Chief Executive Officer of DiscoveryBioMed. “With our academic partners at the University of Alabama at Birmingham and at Johns Hopkins University School of Medicine, we stand ready to test lead compounds for safety and efficacy in both CF and hypertensive animal models.”
DBM has adapted a known electrical bioassay method to be high-throughput screening friendly, a necessary solution to bring the bioassay to the molecular target endogenous to the apical cell membrane of polarized renal and respiratory epithelia. The molecular target in play for this drug discovery program is an epithelial ion channel that is the rate-limiting step for the handling of salt in the distal portions of the kidney and in the respiratory tract. When over-active, this sodium channel can cause dehydration of the airways and too much salt in the blood, leading to high blood pressure.
“To successfully study this ion channel target, we had to bring the bioassay to the target where it is most comfortable, the apical membrane of a polarized epithelium simulated in in vitro 3D culture,” continued Dr. Schwiebert. “Researchers refer to this target as ‘twitchy’ since it does not behave the same in other experimental systems. It also depends upon factors produced by the epithelium itself to maintain proper activity. DBM brought the assay to the target and remains true to the principle that the target should be endogenous to a human or mammalian epithelial cell system to empower the most biologically-relevant drug discovery program. We believe screening on life-like human cell platforms is essential in development of drugs that ultimately will be provided to human patients.”
Additionally, DiscoveryBioMed has a pair of closely related lead compounds in hand that it will use as a medicinal chemistry platform. Additional hit-to-lead compounds are emerging. At the end of Phase 2, DBM anticipates having pre-clinical animal data and, possibly, proof-of-concept efficacy data in animals and in humans to show to potential out-license partners.
About DiscoveryBioMed, Inc.
DiscoveryBioMed, Inc. is a life sciences and biotechnology company that engages in R&D and services work in cell engineering and production and cell-based drug discovery. The company is located within The Innovation Depot facility in Birmingham, Alabama. Using physiologically relevant cell culture models preferably derived from normal and diseased adult human cells and tissues, DBM focuses on finding therapeutic compounds for a variety of human diseases. It also applies this custom human cell-based approach to its “fee-for-service” support to researchers in allied areas and currently serves clients both locally in Alabama as well as in 11 other states in the US currently. For more information, visit the DBM website at www.discoverybiomed.com.
Determining the prospective strategies for Implementing Clinical trials in India & South Asia - Today’s Hottest Market
18th - 20th May 2009, The Park, New Delhi, India
Key Speakers • Chandrashekhar Potkar, Director, Medical and Regulatory Affairs, Pfizer, India
• Viraj Rajadhyaksha, Senior Manager, Operations, Planning & Mgmt Clinical Research, Pfizer, India
• Rajesh Karan, Regional Head of Translational Medicine & Scientific Operations, Novartis, India • Anirban Roy Chowdhury, Clinical Research Manager, AstraZeneca, India • Subbaraju Sagi, Senior Sales Consultant,Oracle Health Sciences • Mark Engel, Chairman, ExcelPharmaStudies, China • Celestine Juliet, Project Manager, Cipla
• Krathish Bopanna, Senior Vice President, Acunova
• Nermeen Varawalla, Vice President, Scientific & Medical Affairs, PRA International, London
• Paula Mumby, Director, i3 Pharma Resourcing
• Dan Zhang, CEO, Fountain Medical Development, China
• Dalvin Ni, VP, Fountain Medical Development, China
• Milind Antani, Head-Pharma LifeSciences group, Nishith Desai • Arun Bhatt, President, Clininvent Research
• Arani Chatterjee, Vice President,
India has all the competitive advantages for conducting clinical trials. As the country is increasingly becoming a favored destination for clinical trials, a gap analysis needs to be done to scale up all resources for clinical trials. This scale up is essential for India to cope with the large global clinical trial projects. It is no coincidence over the last decade or more of economic liberalization, and years of unprecedented growth, that India and parts of South Asia are becoming a preferred clinical research destination for multinational pharmaceutical and biotechnology corporations.
Clinical Trials Summit 2009 will discuss the on-going pressing concerns faced in clinical trials operations, addressing the risks, timeline and budget constraint, whilst effectively tackling key challenges in overcoming trials agreement and site contract negotiation hurdles. This year, the operational element of trial site management, strategic partnership with CROs and SMOs, patient, talent & investigators management will be discussed in order to improve and optimize the overall drug development effectiveness and ROI. Find out how to implement and benefit from electronic data management & monitoring cost effectively. This event will be shared by leading industrial practitioners across the region to promote practical discussions; especially on the know-how to manage needs, variability of different countries and institutions to enhance clinical operational excellence and vigilance. Delegates will have the opportunity to learn, network and benchmark against the global top pharmas and local industry leaders on the best practices in talent, site, budget and performance management in clinical trials. The conference aims to provide a detailed analysis of what it takes to conduct clinical trials from a biopharmaceuticals and vaccines perspective in India and China and also addressing risk/benefit balance, anecdotal experiences of the multinational pharmaceutical industry in India and China, selection and role of CROs, logistics of operations, clinical trials management, government policies (including IPR issues) and pharmacovigilance.
Reasons to register today:
• How can you take advantage of the global market for clinical trials?
• Improving and optimizing site management and overall productivity of clinical operations
• Optimising clinical trials operation effectiveness and ROI through strategic site, patient, data and risk management in the regulated markets
• Identify the data management, CMC supply chain, operational requirements and CRO infrastructure in India and South Asia
• Gaining insights on future forwards of clinical trials and valuing its potential
• Discover how to improve your supplier-client relationships
• Complete trials on schedule and budget by learning to overcome hurdles in investigator/patient recruitment
• What are the issues with off-shoring trials to countries such as India & South Asia? What are the ways to overcome them?
• Explore innovative strategies for outsourcing, what you should be looking for in a CRO?
• Working with limited budget to ensure on time study completion
• Escalating patient recruitment and improving patient retention to save cost and reduce lead-time
• Maximizing trials results through overseas multinational/multi-centric trials
• Avoiding potential pitfalls of trials agreement
• Motivating and managing clinical project teams to improve timeline and progress
Who should attend? From pharmaceutical, biotech and CRO’s: Directors and Heads of: • Clinical Research & Development
• Clinical Research Services
• Clinical Operations
• Clinical Data Management
• Clinical IT
• Clinical Trials
• Medical Affairs
• Regulatory Affairs
• Compliance
• Quality Control/Assurance/GCP
• Clinical Study Design
• Safety Surveillance
• Subject Recruitment
• E-Clinical Systems
Location The Park, New Delhi
15 Parliament Street, New Delhi, 110001
Tel: +91 011 2374 3000 Ext 1902, Fax: +91 11 233629320
BERKELEY, Calif.–(BUSINESS WIRE)–Plexxikon Inc. today announced the issuance of key composition-of-matter patents covering novel compounds discovered through the company’s Scaffold-Based Drug Discovery™ platform. Plexxikon’s pipeline of preclinical and clinical stage product opportunities currently span potential treatments for cardio-renal disease, CNS disorders, inflammation, metabolic disease and oncology. Two of the three recently issued patents (U.S. patents no. 7,498,342 and no. 7,504,509) cover compounds derived from the company’s discovery efforts to target protein kinases for the treatment of multiple indications including oncology and inflammation. The third patent (U.S. patent no. 7,476,746) covers novel compounds from the company’s PPAR (peroxisome proliferator-activated receptor) program yielding novel therapeutic opportunities for metabolic disorders and other diseases.
“We are pleased to be adding these additional patents to our growing and broad intellectual property portfolio,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “Plexxikon’s novel approach to drug discovery has enabled the company to advance multiple first-in-class drug candidates which are covered by strong intellectual property, and as a result, to secure significant pharmaceutical industry interest in our programs.”
In contrast to fragment-based approaches, Plexxikon’s platform has generated multiple product opportunities by mining the relatively unexplored chemical space of scaffold-like cores and by utilizing co-crystallography early in the discovery process to guide chemical optimization of these scaffolds. Further, the company has developed methods to make highly selective kinase inhibitors as yet rarely seen. Plexxikon has demonstrated the ability to develop selectivity between two targets with as little as one amino acid difference in their catalytic domains. This capability has created the opportunity for the development of new targeted drugs not only for oncology, but also for chronic disease indications outside oncology where safety hurdles are even higher. To date, Plexxikon’s platform has led to the development of a targeted medicine for the treatment of melanoma, a drug candidate for polycystic kidney disease (PKD), an oral agent for rheumatoid arthritis and a broad spectrum oral diabetic therapeutic, all representing novel agents addressing significant unmet needs.
Dr. Prabha Ibrahim Promoted to Vice President of Chemistry
In other news, Prabha N. Ibrahim, Ph.D., was promoted to the position of vice president of chemistry, bringing over 15 years of experience to her position. As head of chemistry since 2002, she has played a key role in building the company’s synthetic and medicinal chemistry capabilities leading to the discovery of Plexxikon’s novel drug candidates now in the clinic and in preclinical development. Prior to Plexxikon, Dr. Ibrahim was a senior scientist at CV Therapeutics, where she was responsible for the identification and development of preclinical candidates for cardiovascular indications. She also previously worked at Amgen, where she played an integral role in small molecule drug discovery for inflammation therapeutics. Dr. Ibrahim earned her Ph.D. at the University of Victoria, Canada, and was a Welch Foundation Fellow at Rice University in Houston.
Plexxikon Profile
Plexxikon is a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s clinical stage programs include PLX4032 for the treatment of melanoma and colorectal cancer, PLX5568 for the treatment of PKD and PLX204 for the treatment of diabetes. Among the company’s preclinical development programs, candidates are being developed for the treatment of rheumatoid arthritis, multiple sclerosis and other autoimmune diseases.
Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform is being applied to build a pipeline of product opportunities in multiple therapeutic areas. This discovery process integrates multiple state-of-the-art technologies, including structural screening as one key component that provides a significant competitive advantage over other drug discovery approaches. To date, the company has discovered a portfolio of clinical and preclinical stage compounds in varied disease areas addressing significant unmet needs in each therapeutic category.
Plexxikon is seeking pharmaceutical and biotechnology partners for select collaboration opportunities. For more information, please visit www.plexxikon.com.
San Francisco, CA - GTCbio Announces its 4th Annual Assay Development and Screening Conference taking place June 8-9, 2009. As compounds derived from high throughput screening increasingly find their way into clinical trials, drug screening has become widely accepted as a critical step in the drug discovery process. After more than a decade of rapid growth, tremendous progress has been made in assay technology, laboratory automation, and informatics. These technological developments have not only facilitated a drastic increase in throughput and efficiency in drug screening, but have also provided novel solutions in other areas of drug discovery and development. As screening has also become prominent in biological research, screening facilities have become increasingly popular in academic institutions.
As the pharmaceutical industry continues to face the challenges of developing more new chemical entities and reducing the cost of R&D, the demand for novel technologies and creative approaches for improving the efficiency of screening has intensified. Cell-based assays used in compound screening and high-content screening technologies have gained popularity in the industry. Years of intensive research have finally resulted in label-free technologies in the drug screening market place. These technologies provide new ways of interrogating cellular and molecular binding events and enable orthogonal screening approaches to drug targets.
The goal of the 4th annual Assay and Screening Technologies Conference is to provide a forum for academics and professionals in the drug discovery industry to stay abreast of exciting new developments in assay technologies while exchanging ideas and developing more efficient approaches to the drug discovery and development process.
For more information, visit http://gtcbio.com/conferenceDetails.aspx?id=123
HOPKINTON, Mass., March 19 /PRNewswire-FirstCall/ — Caliper Life Sciences, Inc. (NASDAQ: CALP) , a leading provider of tools and services for drug discovery and life sciences research, today announced that the United States Environmental Protection Agency (EPA) presented initial analyses of Phase I data generated by Caliper Discovery Alliances and Services (CDAS) under the EPA’s ToxCast(TM) screening program at the annual meeting of the Society of Toxicology (SOT) held this week in Baltimore, MD. Separately, the EPA notified Caliper that it has exercised the first additional option year under Caliper’s ToxCast contract with the EPA. Task orders under this contract have already generated approximately $3.5 million in total revenues for Caliper since the initiation of the contract in April, 2007, $1.2 million of which was recognized in 2008.
“We are pleased with the preliminary findings presented by the EPA,” said Kevin Hrusovsky, President and CEO of Caliper Life Sciences. “These results, coupled with the EPA’s third year option exercise, reinforce the likelihood for Phase II efforts to begin at Caliper in the third quarter of this year, which supports our expectation of receiving approximately $3 million of service task orders under this contract in 2009.”
Caliper works with the EPA under its ToxCast initiative to develop new in vitro (laboratory) approaches to identify chemicals that are potentially toxic to the environment. The initial phase of the EPA ToxCast program was aimed at creating a database of in vitro assay data on a broad set of compounds for which in vivo (animal) safety data already existed. Key goals for this phase were to assess overall data quality and establish that the database was predictive of in vivo toxicity profiles. Initial analyses of the data generated at CDAS indicate that the goals for high quality data and potential predictive power have been met. For the 11 replicate controls included in the initial 320 compound set, there was greater than 99% concordance in the screening results across 240 assays tested, and more than 200 correlations between the in vitro results generated at CDAS and in vivo toxicity parameters have already been identified. In addition, 75% of the assays tested showed activity for one or more compounds, reinforcing the need for broad in vitro profiling.
“We believe this data presentation validates the importance of in vitro profiling as a tool for predicting potential toxicity liabilities of compounds and highlights the high quality data generated by Caliper,” said David Manyak, Ph.D., Executive Vice President of Discovery Services at Caliper Life Sciences. “Our access to the entire Phase I ToxCast database makes Caliper an ideal partner for collaborative data mining projects. We also believe that the assay screening panel employed by Caliper for the ToxCast initiative will be broadly applicable for product development programs within the agricultural chemical and pharmaceutical industries.”
The ultimate goal of the ToxCast program is to develop a set of predictive in vitro assays that can supplement or replace in vivo tests currently used for regulatory approval of new environmental chemicals. If successful, the ToxCast initiative will reduce the cost and improve the speed of regulatory approval of new environmental chemicals. More extensive data analysis from the EPA is expected in mid-May of this year.
About Caliper Life Sciences
Caliper Life Sciences is a premier provider of cutting-edge technologies enabling researchers in the life sciences industry to create life-saving and enhancing medicines and diagnostic tests more quickly and efficiently. Caliper is aggressively innovating new technology to bridge the gap between in vitro assays and in vivo results and then translating those results into cures for human disease. Caliper’s portfolio of offerings includes state-of-the-art microfluidics, lab automation & liquid handling, optical imaging technologies, and discovery & development outsourcing solutions. For more information please visit www.caliperLS.com.
BERKELEY, Calif.–(BUSINESS WIRE)–Plexxikon Inc. today announced the issuance of key composition-of-matter patents covering novel compounds discovered through the company’s Scaffold-Based Drug Discovery™ platform. Plexxikon’s pipeline of preclinical and clinical stage product opportunities currently span potential treatments for cardio-renal disease, CNS disorders, inflammation, metabolic disease and oncology. Two of the three recently issued patents (U.S. patents no. 7,498,342 and no. 7,504,509) cover compounds derived from the company’s discovery efforts to target protein kinases for the treatment of multiple indications including oncology and inflammation. The third patent (U.S. patent no. 7,476,746) covers novel compounds from the company’s PPAR (peroxisome proliferator-activated receptor) program yielding novel therapeutic opportunities for metabolic disorders and other diseases.
“We are pleased to be adding these additional patents to our growing and broad intellectual property portfolio,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “Plexxikon’s novel approach to drug discovery has enabled the company to advance multiple first-in-class drug candidates which are covered by strong intellectual property, and as a result, to secure significant pharmaceutical industry interest in our programs.”
In contrast to fragment-based approaches, Plexxikon’s platform has generated multiple product opportunities by mining the relatively unexplored chemical space of scaffold-like cores and by utilizing co-crystallography early in the discovery process to guide chemical optimization of these scaffolds. Further, the company has developed methods to make highly selective kinase inhibitors as yet rarely seen. Plexxikon has demonstrated the ability to develop selectivity between two targets with as little as one amino acid difference in their catalytic domains. This capability has created the opportunity for the development of new targeted drugs not only for oncology, but also for chronic disease indications outside oncology where safety hurdles are even higher. To date, Plexxikon’s platform has led to the development of a targeted medicine for the treatment of melanoma, a drug candidate for polycystic kidney disease (PKD), an oral agent for rheumatoid arthritis and a broad spectrum oral diabetic therapeutic, all representing novel agents addressing significant unmet needs.
Dr. Prabha Ibrahim Promoted to Vice President of Chemistry
In other news, Prabha N. Ibrahim, Ph.D., was promoted to the position of vice president of chemistry, bringing over 15 years of experience to her position. As head of chemistry since 2002, she has played a key role in building the company’s synthetic and medicinal chemistry capabilities leading to the discovery of Plexxikon’s novel drug candidates now in the clinic and in preclinical development. Prior to Plexxikon, Dr. Ibrahim was a senior scientist at CV Therapeutics, where she was responsible for the identification and development of preclinical candidates for cardiovascular indications. She also previously worked at Amgen, where she played an integral role in small molecule drug discovery for inflammation therapeutics. Dr. Ibrahim earned her Ph.D. at the University of Victoria, Canada, and was a Welch Foundation Fellow at Rice University in Houston.
Plexxikon Profile
Plexxikon is a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s clinical stage programs include PLX4032 for the treatment of melanoma and colorectal cancer, PLX5568 for the treatment of PKD and PLX204 for the treatment of diabetes. Among the company’s preclinical development programs, candidates are being developed for the treatment of rheumatoid arthritis, multiple sclerosis and other autoimmune diseases.
Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform is being applied to build a pipeline of product opportunities in multiple therapeutic areas. This discovery process integrates multiple state-of-the-art technologies, including structural screening as one key component that provides a significant competitive advantage over other drug discovery approaches. To date, the company has discovered a portfolio of clinical and preclinical stage compounds in varied disease areas addressing significant unmet needs in each therapeutic category.
Plexxikon is seeking pharmaceutical and biotechnology partners for select collaboration opportunities. For more information, please visit www.plexxikon.com.
International symposium “Stem Cell Transplantation in Multiple Sclerosis: Sharing the Experience” will be held on October 5th, 2009 in Moscow, Russia. Symposuim Organizers are Pirogov National Medical Surgical Center, National Center for Research and Treatment of Autoimmune Diseases, Russian Cooperative Group for Cellular Therapy, New Jersey Center for Quality of Life and Health Outcomes Research.
The symposium will be the first special meeting fully meant to discuss the state-of-the-art and perspectives of the new and quite promising method of multiple sclerosis treatment - high dose immunosuppressive therapy + autologous hematopoietic stem cell transplantation. It intends to share the newly acquired knowledge in the field, to discuss challenges and perspectives of the method, and to develop collaborative projects. The topics to be covered within the symposium include:
“ Regimens of conditioning: Immunoablation or immunosupression?
“ Types of transplantation: autologous or allogenic?
“ Posttransplant immunological reconstitution
“ Side effects
“ Outcome measures: clinical, imaging, patient-reported outcomes
“ Posttransplant neurorehabilitation
“ Long-term follow-up results
“ Proposals for cooperative studies
Neurologists, immunologists, transplantologists, hematolosits, specialists in stem cell research are invited to participate in the Symposium.
Key dates:
1 March 2009 - Deadline for abstract submission
1 April 2009 - Deadline for early registration
Names World-Renowned Cancer Drug Expert Dr. Joseph Rubinfeld as Chief Scientific Advisor
LOS ANGELES–(BUSINESS WIRE)–CytRx Corporation (NASDAQ: CYTR) today unveiled its corporate strategy to focus its internal resources on the clinical development of oncology drug candidates tamibarotene and INNO-206, which the Company believes offer the greatest mix of near-term and medium-term revenue potential among its clinical assets. CytRx will pursue partnerships to advance the clinical development of INNO-406 (bafetinib) and its clinical molecular chaperone portfolio, where it continues to see significant future revenue potential. The Company further intends to use its proprietary high-throughput, high-content drug screening Master Chaperone Regulator Assay (MaCRA) platform to discover additional molecular chaperone drug candidates, including those that may inhibit cancer growth, which will support internal efforts to build an oncology drug franchise or future out-licensing possibilities.
CytRx also announced that Board of Directors’ member Dr. Joseph Rubinfeld has accepted the additional responsibility of Chief Scientific Advisor, and will consult on all aspects of the Company’s oncology development programs while serving as an important interface between the Company and investors, clinicians and industry thought leaders. Dr. Rubinfeld brings substantial expertise in oncology and drug development through his distinguished career. Dr. Rubinfeld was employed at Bristol-Myers Company International Division as Vice President and Director of Research and Development. While at Bristol-Myers, Dr. Rubinfeld was instrumental in licensing the original anticancer line of products, including Mitomycin and Bleomycin. Among other accomplishments, he was among the four co-founders of Amgen, Inc., and founded SuperGen, Inc., where he previously served as CEO, President and Chief Scientific Officer. In his career he has been instrumental in the development of several blockbuster cancer drugs including cisplatinum, etoposide, erythropoietin, decibitene and pentostatin, and the antibiotics amoxicillin and cefadroxil.
Steven A. Kriegsman, CytRx President and CEO said, “We feel that our stockholders are best served by a focus on potential therapeutics for cancer. We believe tamibarotene has strong potential as a revenue generator with a high likelihood for rapid U.S. approval as a third-line treatment for acute promyelocytic leukemia (APL). Our view is based on the substantial clinical history of tamibarotene as an approved treatment of relapsed APL, in Japan and the existing special protocol assessment (SPA) in place with the U.S. Food and Drug Administration (FDA) for our ongoing U.S. registration clinical trial. We are accelerating enrollment in this clinical trial, with the expectation of filing an NDA with the FDA as early as 2010. We are also taking steps to move into a Phase 2 clinical trial with INNO-206, our highly promising targetable pro-drug for the commonly prescribed chemotherapeutic doxorubicin. We believe that INNO-206 could be effective in a wide variety of cancers, including small cell lung cancer, sarcoma, breast and ovarian cancer and Non-Hodgkins Lymphoma.
“Importantly, we expect that we have ample financial resources with our current cash position and investment in RXi Pharmaceuticals Corporation to support this strategy,” according to Mr. Kriegsman. “We have strong oncology expertise within CytRx and are delighted that Dr. Joseph Rubinfeld, our long-time board member who has enjoyed an illustrious career developing cancer drugs, will be taking a leadership role in our oncology programs.”
Dr. Rubinfeld said, “Having reviewed the extensive data on tamibarotene and INNO-206, I am excited about the potential for these two cancer drug candidates and look forward to working closely with the CytRx management team to advance their clinical development to potential commercialization. I am also encouraged by the Phase 1 data we announced earlier this month with INNO-406, now known as bafetinib, which demonstrated positive, clinical responses in 35% of patients with refractory chronic myeloid leukemia. I believe these results will be instrumental in our search for a partnership for bafetinib.”
Mr. Kriegsman added, “We also stand behind our view that our orally administered molecular chaperone drug candidates, arimoclomol and iroxanadine, provide enormous potential in addressing large, underserved markets and are convinced that the prudent course to maximize stockholder value in this economic climate is to pursue pharmaceutical partners to share additional development costs for these longer-term programs. We intend to complete our ongoing arimoclomol animal toxicology studies and work aggressively toward lifting the current clinical hold in order to enable this drug candidate to move back into the clinic. At that point, we will seek partners for further development of arimoclomol as a therapeutic treatment for both ALS and stroke recovery. Additionally, iroxanadine has shown significant potential as a therapeutic treatment for diabetic foot ulcers and other diabetic complications, and based on Phase 2 data, we will pursue potential partnerships in cardiovascular conditions.”
CytRx’s drug portfolio includes the following:
Oncology Drug Candidates:
Tamibarotene: CytRx holds the North American and European rights to tamibarotene, a rationally designed, synthetic retinoid compound designed to potentially avoid toxic side effects of the current first-line APL treatment trans-retinoic acid (ATRA). CytRx is actively enrolling patients in a Phase 2 registration clinical trial, known as STAR-1, with tamibarotene to evaluate its efficacy and safety as a third-line treatment for APL. The registration study is being conducted under a Special Protocol Assessment. The FDA has granted Orphan Drug Designation and Fast Track Designation for the use of tamibarotene in patients with relapsed or refractory APL following treatment with ATRA and arsenic trioxide.
There are currently no approved third-line treatment options for refractory APL patients. CytRx estimates the U.S. market opportunity for tamibarotene in refractory APL at approximately $20 million annually. CytRx scientists are also evaluating clinical strategies for developing tamibarotene as a first-line or second-line APL therapy. The estimated annual market potential in the U.S. and Europe for an expanded label including refractory, maintenance and front-line therapy is $150 million. CytRx also retains an option to expand its licenses for the use of tamibarotene in other cancers including multiple myeloma, myelodysplastic syndrome and certain solid tumors in the U.S., and multiple myeloma, myelodysplastic syndrome and solid tumors, other than hepatocellular carcinoma, in Europe.
INNO-206: This pro-drug derivative of the commonly prescribed chemotherapeutic agent doxorubicin is designed to reduce adverse events by controlling drug release and preferentially targeting the tumor. In a Phase 1 study, INNO-206 was administered in doses at up to six times the standard dosing of doxorubicin without an increase in observed side effects over those historically seen with doxorubicin. Objective clinical responses were seen in patients with sarcoma, breast and lung cancers. The Company plans to evaluate further clinical development of INNO-206 in a wide variety of cancers, including sarcomas, breast and ovarian cancer, and Non-Hodgkins Lymphoma.
INNO-406 (bafetinib): INNO-406 (bafetinib), a potent, orally available, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor, is being evaluated for the treatment of patients with chronic myeloid leukemia (CML) and other leukemias that have a certain mutation called the Philadelphia Chromosome (Ph+) and are intolerant of or resistant to imatinib (Gleevec®) and second-line tyrosine kinase inhibitors (i.e. dasatinib (Sprycel®) and nilotinib (Tasigna®)). In November 2008, CytRx announced that bafetinib demonstrated positive, clinical responses in 35% of patients with CML in Phase 1 clinical testing. The Phase 1 clinical trial was used to determine the optimal dose prior to Phase 2 clinical efficacy testing.
CML is a type of cancer that starts in blood-forming cells of the bone marrow and invades the blood. In 2007, the American Cancer Society estimated that approximately 4,600 new cases of CML were diagnosed in the U.S. and that the number will increase as the population ages. Current estimates are that worldwide CML prevalence will increase by 10,000 patients a year, reaching a population of 110,000 in 2010. The global market will grow to an estimated $5.5 billion by 2012.
Molecular Chaperone Regulation
CytRx is a leader in molecular chaperone regulation technology. The Company currently has two orally administered, clinical-stage, drug candidates and recently discovered a series of additional compounds that may provide a pipeline for additional drug candidates. The Company’s drug candidates are believed to function by regulating a normal cellular protein repair pathway through the activation or inhibition of “molecular chaperones.” Because damaged proteins are thought to play a role in many diseases, activation of molecular chaperones that help to reduce the accumulation of misfolded proteins may have therapeutic efficacy in a broad range of disease states. Similarly, CytRx believes that the inhibition of molecular chaperones that normally help protect cancer cells from toxic misfolded proteins may result in the selective destruction of cancer cells.
Arimoclomol: This molecular chaperone regulator drug candidate is being considered as a treatment for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and stroke recovery. Arimoclomol has been studied in seven Phase 1 and two Phase 2 clinical trials without any significant adverse events. CytRx’s Phase 2b clinical trial with arimoclomol as a treatment for ALS was placed on clinical hold by the FDA in January 2008, unrelated to any data generated by human studies, and additional preclinical toxicology studies are underway to resolve this issue.
Iroxanadine: CytRx believes that this orally available small molecule compound represents a potentially powerful breakthrough in the treatment of vascular diseases that are caused in part by damage to “vascular endothelium” that lines the inside of blood vessels. CytRx believes that endothelial dysfunction plays a key role in the development of various vascular diseases or their complications including diabetic ulcers, thrombosis, retinopathy, and peripheral artery disease. Preclinical and clinical studies with iroxanadine indicate that it has therapeutic potential for the treatment of cardiovascular atherosclerosis. According to the National Heart, Lung & Blood Institute, atherosclerosis is a leading cause of illness and death in the U.S. and affects approximately 4.6 million people annually.
CytRx San Diego Laboratory: The CytRx San Diego Laboratory is using the Company’s proprietary Master Chaperone Regulator Assay (MaCRA), a cell image-based screening tool that enables the rapid and quantifiable screening of large numbers of small molecule compounds. This technology is used to identify potential drug candidates that modify the activity of a protein known as heat shock transcription factor 1 (Hsf1) and consequently control entire groups of molecular chaperone proteins that repair or degrade toxic misfolded proteins present in diseased cells. Evaluation of the compounds identified in the screen has shown that they exhibit cytoprotective properties in cell culture models of disease. This platform has broad applicability to a range of therapeutic areas, through its ability to identify drug candidates that can either inhibit or amplify molecular chaperone activity. Information related to the development of MaCRA for compound screening was published in the November 2008 issue of the peer-reviewed Journal of Biomolecular Screening.
CytRx Oncology Expertise
Collectively, CytRx’s management and its Board of Directors have brought numerous cancer drugs to market. In addition to Dr. Rubinfeld, the senior managers and directors of CytRx who hold significant oncology experience include: Max Link, Ph.D., Chairman of the Company’s Board of Directors since 1996, who served for a number of years as Chairman and CEO of Sandoz Pharma as well as a director of Alexion Pharmaceuticals, Inc., Celsion Corporation and Discovery Laboratories, Inc.; Jack R. Barber, Ph.D., Chief Scientific Officer, who has significant R&D experience in oncology at Immusol and Viagene, where he most recently served as Head of Oncology; and Shi Chung Ng, Ph.D., Senior Vice President of Research and Development, who has substantial R&D experience at companies such as Abbott and ArQule, Inc., and most recently served as Vice President of Molecular Oncology at Ligand Pharmaceuticals.
About CytRx Corporation
CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The CytRx drug development pipeline includes programs in clinical development for cancer indications, including tamibarotene in a registration study for the treatment of acute promyelocytic leukemia (APL). CytRx is developing two drug candidates based on its industry-leading molecular chaperone technology, which aims to repair or degrade misfolded proteins associated with disease. The Company owns and operates a research and development facility in San Diego. CytRx also maintains a 45% equity interest in publicly traded RXi Pharmaceuticals, Inc. (NASDAQ: RXII). For more information on the Company, visit www.cytrx.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks relating to the outcome or results of any pre-clinical or clinical testing of CytRx’s potential oncology or molecular chaperone drug candidates, including tamibarotene as a third-line treatment for APL, risks related to CytRx’s ability to enter into partnerships to advance the clinical development of INNO-406 and its clinical molecular chaperone portfolio, uncertainties related to the impact of the FDA’s clinical hold on the Company’s arimoclomol clinical trial for ALS on the timing and ability to resume clinical testing at the desired dosage of arimoclomol, the risk that any requirements imposed on the Company’s planned clinical trial designs for ALS or stroke recovery by the FDA as a result of the concerns expressed in their clinical hold of the Company’s ALS program might adversely affect the Company’s ability to demonstrate that arimoclomol is efficacious in treating ALS or stroke patients or cause the Company to cancel one or both of those trials, risks related to CytRx’s need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, risks related to the future market value of CytRx’s investment in RXi and the liquidity of that investment, and the risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx’s most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Combination of Proprietary Drug Targets and Unique Technologies to Create Range of New Therapeutic Antibodies
MUNICH, GERMANY — (Marketwire) — 11/26/08 — MorphoSys AG (FSE: MOR; Prime StandardSegment, TecDAX) and Galapagos NV (Euronext: GLPG) announced today the launch of a long term co-development alliance aimed at discovering and developing antibody therapies based on novel modes of action in bone and joint disease, including rheumatoid arthritis, osteoporosis and osteoarthritis.
The alliance spans all activities from target discovery through to completion of proof of concept clinical trials of novel therapeutic antibodies. Both companies will contribute their core technologies and expertise to the alliance. Galapagos will provide antibody targetsimplicated in bone and joint disease in addition to its adenoviral target discovery platform to discover further targets for antibody development.MorphoSys will contribute its HuCAL antibody technologies to generate fully human antibodies directed against these targets. The initial goal is to further validate the targets through disease-specific in vitro and in vivotesting of the antibodies. After successful validation, the alliance will select antibody programs for pre-clinical and clinical development.Following proof of concept in human clinical trials, programs will be partnered for subsequent development, approval and marketing.
Under the terms of the agreement, Galapagos and MorphoSys will share the research and development costs, as well as all future revenues equally.Decisions will be made by a Joint Steering Committee comprising members of both companies. An initial set of three targets implicated in bone and joint disease has been selected for the collaboration, and Galapagos isalready commencing with production of these proteins for the alliance.Generation of antibodies directed against these targets will start in2009. More targets will be selected using Galapagos’ target discovery platform to fuel the alliance in the coming years. If successful, the first antibody programs based on these novel targets could enter the clinic within four to five years.
“With this alliance, we are adding a biologics strategy to our small molecule drug discovery. Galapagos is the world leader in discovery ofnovel targets, and this alliance with MorphoSys enables us to explore the potential of proprietary antibody targets. Antibody approaches have provento be successful in developing new therapies for major diseases, including rheumatoid arthritis. Having both approaches, small molecules andantibodies, to fill our product pipeline in bone and joint disease willfurther establish Galapagos as the leader in this field,” said Onno van deStolpe, Chief Executive Officer of Galapagos. “With our cash position and revenue streams from both BioFocus DPI and our pharma alliances, we are in a good financial position to enter into this alliance to create value for our shareholders.”
“This alliance represents a major step in our efforts to gain access to novel antibody targets for proprietary drug development in disease areas with a high unmet medical need. The partnership with Galapagos combines both the scientific and financial strength of two leading companies in their space,” said Dr. Simon Moroney, Chief Executive Officer of MorphoSys. “We are excited to combine our broad antibody expertise with Galapagos’ target discovery capabilities and disease know-how to form a successful partnership. The access to novel disease-related target molecules from a renowned partner accelerates the expansion of our proprietary antibody pipeline. This alliance also complements our development efforts in the field of inflammation and arthritis includingour lead program MOR103.”
With this strategic alliance, MorphoSys gains access to a proven target discovery engine as well as to Galapagos’ expertise in bone and joint disease, to support its therapeutic antibody pipeline expansion. The threemain indications of bone and joint disease - rheumatoid arthritis,osteoporosis and osteoarthritis - all represent very significant marketopportunities with several million people affected worldwide and combinedsales of drug treatments of more than US$ 15 billion in 2006.
Through the alliance with MorphoSys, Galapagos enters the rapidly growingmarket for therapeutic antibodies. In 2007, total sales for the 20antibody drugs on the market amounted to more than US$ 25 billion andantibody sales are forecast to increase to approximately US$ 50 billion in 2013. Fully human antibodies are recognized as the next generation and the majority of therapeutic antibodies currently in development are humanized or fully human. The average industry timescale from discovery to pre-clinical development of antibody therapies is only two to three years, considerably shorter than the average six years for small molecules.Antibodies also incur lower attrition rates than small molecules.
Galapagos and MorphoSys will conduct a conference call and live audio webcast today at 02:00 p.m. CET (8:00 a.m EST) to provide detailed information on the alliance.Dial-in number for the Conference Call (listen-only):Germany & U.K. residents: +32 2 401 53 06For U.S. residents: +1 866 931 1567 Please dial in 10 minutes before the beginning of the conference.Approximately two hours after the press conference, the archived webcast will be available for replay of the conference on http://www.morphosys.comand http://www.glpg.com.
For further information please contact: Dr. Claudia Gutjahr-Löser, Head ofCorporate Communications & Investor Relations, Tel: +49 (0) 89 / 899 27-122, gutjahr-loeser@morphosys.com or Mario Brkulj, Manager CorporateCommunications & Investor Relations, Tel: +49 (0) 89 / 899 27-454,brkulj@morphosys.com
About Galapagos:
Galapagos (Euronext Brussels: GLPG; Euronext Amsterdam: GLPGA; OTC: GLPYY)is a drug discovery company with pre-clinical programs in bone and jointdiseases and bone metastasis. Its BioFocus DPI division offers a fullsuite of target-to-drug discovery products and services to pharmaceuticaland biotech companies, encompassing target discovery and validation,screening and drug discovery through to delivery of pre-clinicalcandidates. BioFocus DPI also provides adenoviral reagents for rapididentification and validation of novel drug targets, compound libraries fordrug screening as well as chemogenomics and ADMET database products toselect targets and compounds. Galapagos currently employs about 450 peopleand operates facilities in six countries, with global headquarters inMechelen, Belgium. More information about Galapagos and BioFocus DPI canbe found at www.glpg.com and www.biofocusdpi.com.
About Galapagos’ target discovery technology:
Galapagos’ target discovery engine is based on adenoviruses thatefficiently introduce human gene sequences into a wide variety of humancells to knock-down specific proteins. High-throughput assays thatrepresent a selected human disease state are then used to functionallyselect for those proteins that have a causative effect in those models ofhuman disease. After rigorous validation of these protein targets, theyform the basis for the development of novel drugs.
About MorphoSys:
MorphoSys is a publicly traded biotechnology company focused on thegeneration of fully human antibodies as a means to discover and developinnovative antibody-based drugs against life-threatening diseases.MorphoSys’s goal is to establish HuCAL as the technology of choice forantibody generation in research, diagnostics and therapeutic applications.The Company currently has therapeutic and research alliances with themajority of the world’s largest pharmaceutical companies includingBoehringer Ingelheim, Centocor/Johnson & Johnson, Novartis, Pfizer andRoche. Within these partnerships, more than 50 therapeutic antibodyprograms are ongoing in which MorphoSys participates through exclusivelicense and milestones payments as well as royalties on any end products.Additionally, MorphoSys is active in the antibody research market throughits AbD Serotec business unit. The business unit has operations in Germany(Munich), the U.S. (Raleigh, NC) and U.K. (Oxford). For further informationplease visit http://www.morphosys.com/
HuCAL® and HuCAL GOLD® are registered trademarks of MorphoSys AG
Diagnosing and treating Cushing’s syndrome is sometimes just as difficult as it was 70 years ago.
For as long as it has been described, Cushing’s syndrome has presented physicians with a problem. Harvey Cushing first described it in 1932, and the diagnosis, differential diagnosis and treatment of Cushing’s have remained a major challenge for endocrinologists ever since.
Though uncommon, it is difficult to consider Cushing’s syndrome a rare occurrence. New research has shown Cushing’s syndrome to have a substantially higher prevalence than previously thought. Unexpected endogenous hypercortisolism may occur in 0.5% to 1% of patients with hypertension, 2% to 3% with poorly controlled diabetes, 6% to 9% with incidental adrenal masses and 11% with osteoporosis and vertebral fractures.
“We are gaining an appreciation that Cushing’s is more common than it was once believed to be,” said Mary Ruppe, MD, endocrinologist at the University of Texas Health Science Center at Houston, and program committee chair of the Women in Endocrinology organization. “This fact points to the need for data regarding the value of the different diagnostic approaches and for data regarding treatment/outcomes in populations with Cushing’s.”
As most of the characteristics of Cushing’s are common in the general population, including obesity, depression and hypertension, it is extremely difficult for endocrinologists to decide on who should be screened for the disorder. A recent clinical review by Hershel Raff, PhD, and James W. Findling, MD, noted that as the number of patients in these high-risk groups continues to increase, the need for a sensitive and specific diagnostic test for Cushing’s syndrome has become paramount.
The three most commonly performed diagnostic studies for Cushing’s syndrome — urine-free cortisol, low-dose dexamethasone suppression test and the nocturnal salivary cortisol — are also not without hurdles. All three have been shown to produce false positives and false negatives.
Approximately 80% of patients with Cushing’s syndrome have an adrenocorticotropic-secreting neoplasm from a pituitary tumor (Cushing’s disease) or a nonpituitary neoplasm, and the treatment of Cushing’s disease remains challenging for both endocrinologists and neurosurgeons as well. Transsphenoidal surgery is currently the standard treatment of choice in patients, but achieving surgical remission has been difficult as well.
“Cushing’s syndrome is a very rare but important diagnosis for the patient and endocrinologist. Confirming the diagnosis may be challenging, and before embarking on a costly set of tests, the endocrinologist should be reasonably assured that the patient indeed requires diagnostic exclusion by rigorous screening methods,” said Shlomo Melmed, MD, senior vice president of Academic Affairs at Cedars Sinai Medical Center, Los Angeles, and an Endocrine Today editorial board member
.
With more than 7.5 decades of research since Dr. Cushing’s discovery, what are the best methods of diagnosis and treatment for Cushing’s syndrome? Endocrine Today talked with leading researchers in the field to uncover the current trends in Cushing’s syndrome treatment.
Screening process
Laurence Katznelson, MD, associate professor of medicine and neurosurgery at Stanford University, and medical director of the pituitary program at Stanford Hospital and Clinics, explained to Endocrine Today the difficulty of deciding who should be screened for Cushing’s syndrome. For instance, although the syndrome is associated with multiple comorbidities, including obesity, hypertension and depression, endocrinologists should be prepared to delve a little deeper into the symptoms to see if they warrant a screening test.
“The presence of Cushing’s syndrome should be considered if these medical conditions are present, though diagnostic testing should be performed only in subjects who have signs favoring Cushing’s, such as demonstration of objective proximal weakness, spontaneous ecchymoses and violaceous striae,” Katznelson said.
“For example, central obesity with supraclavicular and dorsicervical fat pads would favor a diagnosis of Cushing’s syndrome, in contrast to the presence of generalized obesity,” he said.
Raff and Findling noted in a recent clinical review that endogenous cortisol excess also leads to fairly specific catabolic effects — including the thinning of the skin with easy bruising, abdominal striae, poor wound healing, immune suppression, rib fractures, hirsutism in women, acne and muscle wasting leading to proximal muscle weakness.
“There is no clear guideline,” said Roberto Salvatori, MD, associate professor of medicine in the division of endocrinology at Johns Hopkins University School of Medicine. “You need to keep your mind open.”
“Sometimes Cushing’s is obvious. Sometimes, when it is mild, it may not be diagnosed for many years. One must screen a lot of patients to find one with Cushing’s. However, anytime a physician thinks about the possibility of a patient having the disease, work-up should be initiated,” he said.
Testing options
Opinions varied when Endocrine Today asked researchers which of the three tests for Cushing’s syndrome was most reliable.
“No test is 100% sensitive or specific,” Salvatori said. “I always use two, sometimes three, screening tests.” However, Salvatori noted he feels the night-time salivary cortisol test is the most reliable and easy to obtain.
Raff and Findling described the measurement of free cortisol in a 24-hour urine collection as being long considered the gold standard for the diagnosis of endogenous hypercortisolism. The test relies on the concept that as daily production of cortisol is increased, the free cortisol filtered and not reabsorbed or metabolized in the kidneys will be increased. They noted that current research has shown that many patients with mild Cushing’s syndrome do not have elevations of urine-free cortisol, “making it a poor screening test for this condition.”
The low-dose dexamethasone suppression test relies on the concept that the correct dose of dexamethasone will suppress ACTH, and cortisol will release in normal patients while patients with corticotroph adenomas will not suppress below a specified cut off. Raff and Findling noted that because of the significant variability of the biological behavior of corticotroph adenomas, research has shown that neither the overnight 1-mg dexamethasone suppression test nor the two-day low-dose dexamethasone suppression test appears to be reliable using the standard cutoffs for serum cortisol.
According to Raff and Findling, there is no diagnostic test used in the evaluation of Cushing’s syndrome that performs better than the late night/midnight salivary cortisol method. The concept is based on the fact that patients with mild Cushing’s syndrome fail to decrease cortisol secretion to its nadir at night. However, they still acknowledged that many factors, such as stress, sleep disturbances and psycho-neuroendocrine may falsely elevate nocturnal cortisol secretion.
“Because each of these tests has associated false positives and negatives, a combination of these tests is often necessary for a valid diagnosis,” Katznelson said. “In the end, these tests need to be considered in the context of a history and physical examination that favors this diagnosis.”
Lynette Nieman, MD, associate director of the Intramural Endocrinology Training Program at the NIH, agreed. “Of the three recommended tests, each is useful in certain conditions,” she said. “I try to stress that the testing should be individualized since some tests are likely to be falsely positive in some situations, eg, a woman on birth control pills is likely to have a high corticosteriod-binding globulin, which might elevate serum cortisol.”
Ruppe said the choice between the tests should be based on patient characteristics that will allow for adequate collection of each sample. “For instance, the use of a late-night salivary cortisol measurement would be suboptimal in an individual who works the third shift and may not have an intact circadian rhythm, or the choice of a 24-hour urinary free cortisol may be suboptimal in an individual with urinary frequency or urinary incontinence.”
Ruppe also noted that one possible improvement would be to improve standardization of the assays across different labs. “Since there is no standardization, the quality of the performance of the assay can vary across different facilities and centers,” she said.
Petrosol sinus sampling
Another controversial topic in the field is whether or not the inferior petrosol sinus should be sampled for an ACTH gradient to distinguish between Cushing’s disease and occult ectopic ACTH syndrome.
The invasive procedure has proven to be relatively safe when performed by experienced radiologists, but not all medical centers have the capability.
A woman with mild hypercortisolism, a normal or slightly elevated plasma ACTH and normokalemia has an approximately 95% likelihood of having Cushing’s disease before any differential diagnostic testing is performed, according to Raff and Findling. In contrast, a male patient with prodigious hypercortisolism of rapid onset, hypokalemia and marked elevations of plasma ACTH may be more likely to have an occult ectopic ACTH-secreting tumor.
About half of patients with ACTH-secreting microadenomas are estimated to have a normal pituitary MRI. In such situations, it is important to perform further testing, particularly an inferior petrosal sinus catheterization, to discern the presence of an ectopic ACTH-producing lesion, according to Katznelson.
“Some people would say that every patient should have it because it is the one best test for the differential diagnosis of ACTH-dependent Cushing’s syndrome,” Nieman said. “However, patients in whom data strongly suggest Cushing’s disease might forego it.”
“In a young woman with an MRI with a definitive adenoma and high-dose dexamethasone test showing less than 60% suppression, it is reasonable to proceed with surgery,” Salvatori said. “But even the International Prostate Symptom Score is not 100% sensitive or specific.” Raff said that he disagrees with the high-dose dexamethasone test.
Fast Facts: Issues at Hand
Transsphenoidal surgery
Currently, transsphenoidal surgery is the primary treatment of Cushing’s disease associated with an ACTH-secreting pituitary tumor. According to recent studies, remission rates after transsphenoidal pituitary microsurgery range from 42% to 86%.
Raff told Endocrine Today that the most important treatment recommendation that an endocrinologist makes to a patient with Cushing’s disease is referral to a neurosurgeon with extensive experience.
“Referral to a neurosurgeon who is highly experienced in this procedure is critical,” Katznelson agreed. He noted that there have been studies demonstrating that both the degree of tumor bulk resection and rates of biochemical remission are increased for all types of pituitary tumors when the surgery is performed by a neurosurgeon with extensive experience in endonasal pituitary surgery.
“In Cushing’s disease, this is especially true,” Katznelson said. “Because the tumors in this disorder are often small, if not microscopic, the surgical strategy may require dissection through the gland. In inexperienced hands, this may result in higher rates of hypopituitarism and lower rates of biochemical cure,” Katznelson said.
“There is no doubt that the surgeon’s experience influences the success rate,” Nieman said.
Constantine Stratakis, MD, with the National Institute of Child Health and Human Development, said he agreed, and stressed the importance of confirmation of diagnosis of Cushing’s syndrome prior to a referral to a neurosurgeon.
“There is nothing worse than an inexperienced surgeon operating on a patient with Cushing’s or a surgeon operating on a patient who does not have a firm diagnosis of Cushing’s syndrome,” Stratakis said.
“Surgery offers a reasonable chance for cure in the hands of an experienced neurosurgeon,” said Amir Hamrahian, MD, a staff physician at the Endocrinology Institute at the Cleveland Clinic. “We are currently involved in two studies looking at new medications for medical treatment of patients with Cushing’s syndrome. However, surgery is still the best initial approach for those not cured,” Hamrahian said.
The future
“Medications are the future for patients with inoperable, recurrent Cushing’s syndrome,” Stratakis said, referring to pasireotide (SOM230), a somatostatin analog.
He was part of a study in 2006 examining the in vitro effects of SOM230 on cell proliferation in human corticotroph tumors. Researchers found SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. They concluded that SOM230 may have a role in the medical therapy of Cushing’s disease. Raff said he believes that clinical trials in patients with Cushing’s disease who used SOM230 were not particularly successful. Anne Klibanski, MD, director of the neuroendocrine clinical center at Massachusetts General Hospital and primary investigator of the study, commented that in vitro studies play a critical role in assessing novel targeted pituitary tumor therapies. It is only in rigorous clinical trials that the overall efficacy and risks of such therapies can be established, she suggested.
Constantine Stratakis, MD
“Microsurgical improvements will also be significant, but the major problem right now is the number of patients who are left untreated with recurrent disease,” Stratakis said. “For them, there are very few options other than irradiation, so innovative medical treatments with molecularly designed compounds or targeted to specific receptors and/or functions of the pituitary are the most important advances that I see coming in the near future,” Stratakis said.
According to James Liu, MD, assistant professor of neurologic surgery at Northwestern University Feinberg School of Medicine in Evanston, Ill., the future appears bright in the battle against Cushing’s.
“Technical advances in surgery including endoscopic pituitary surgery and pseudocapsular dissection can improve surgical outcomes,” Liu said.
Katznelson said he hopes the future will bring improved diagnostic strategies important for detecting true Cushing’s syndrome in the presence of multiple comorbidities. He noted that the ongoing research studies involving innovative medical therapeutic strategies that target the corticotroph adenoma itself, or block the effects of cortisol in the periphery, should bring new treatment options in the future.
“These studies will hopefully lead to novel medical options for this syndrome,” Katznelson said. “There have been significant advances in surgery, particularly with the development of minimally invasive, endoscopic surgery that has resulted in both improved biochemical outcomes and patient tolerability.” – by Angelo Milone
For more information:
* Aron DC, Raff H, Findling JW. Effectiveness vs. efficacy: the limited value in clinical practice of high-dose dexamethasone suppression testing in the differential diagnosis of ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 1997:82;1780-1785.
* Batista DL, Zhang X, Gejman R, et al. The effects of SOM230 on cell proliferation and ACTH secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab.2006;91:4482-4488.
* Carroll T, Raff H, Findling JW. Late-night salivary cortisol measurement in the diagnosis of Cushing’s syndrome. Nat Clin Pract Endocrinol Metab. 2008;4:344-350.
* Findling JW, Raff H. Cushing’s syndrome: Important issues in diagnosis and management. J Clin Endocrinol Metab. 2006;91:3746-3753
* Liu JK, Fleseriu M, Delashaw Jr. JB, et al. Treatment options for Cushing’s disease after unsuccessful transsphenoidal surgery. Neurosurg Focus. 2007;23:E8.
* Nieman L. The dexamethasone-suppresssed corticotropin-releasing hormone test for the diagnosis of Cushing’s syndrome: What have we learned in 14 years? J Clin Endocrinol Metab. 2007;92:2876-2878.
* Lad SP, Patil CG, Laws ER Jr, Katznelson L. The role of inferior petrosal sinus sampling in the diagnostic localization of Cushing’s disease. Neurosurg Focus. 2007:23:E2.g
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