Bio Screening Industry News

LONDON–(BUSINESS WIRE)–The drug discovery process has changed dramatically over the past decade and continues to evolve in response to new discoveries and technologies. There is also increasing demand to produce more drug candidates and decrease attrition during drug development. Recent advances in cell culture robotic technology have grown out of the need to maximise efficiency and minimise the possibility of errors, contamination and failure associated with high-throughput cell culture.

In addition, the trends towards assay miniaturisation and multiplexing for high-throughput and ultrahigh-throughput have been triggered by the necessity to reduce development and operational costs. Despite advances in cell based assay technology, numerous bottlenecks still need to be addressed in drug discovery for the identification of novel drug candidates.

New analysis from Frost & Sullivan (http://www.drugdiscovery.frost.com), European Cell Based Assays Markets, finds that the market for cell based assay kits earned revenues of $66.2 million in 2007 and estimates this to reach $220.1 in 2014.

As pharmaceutical companies strive to improve the cost effectiveness of their drug discovery programmes, it is becoming apparent that considerable amounts of money are lost on compounds that fail late in the drug discovery process because of their toxicity.

“Over the past decade, various initiatives have been taken to improve the science of predicting toxicity and improving extrapolation to humans, including the use of cell based assays to enhance predictions,” notes Frost & Sullivan Research Analyst Dr. Laleh Safinia. “The revolution in the drug discovery process has recently demonstrated emerging lab disciplines and technology platforms in the area of cell based assay screening, holding great promise for the discovery of new drug targets.”

Drug targets derived from genomics and proteomics projects have sparked the interest of pharmaceutical, biotechnology and drug discovery companies in screening large numbers of compounds using cell based assays in an ultrahigh-throughput format. Progress and advances in a number of technologies have made the utilisation of live cells in high-throughput screening and high-content screening assays an attractive option in the drug discovery process.

Partnerships and alliances between active participants within this industry will allow the acquisition of new molecules, increase profitability and offer a pipeline of other drugs in development as well as remove some of the bottlenecks within drug discovery.

Cell based assays are an important aspect of the drug discovery process. However, there is a growing need for reliable and robust assay kits to enable the effective standardisation of assays and a reduction in variability. For researchers using automated screening systems, the stability and compatibility of reagents with robotic components is often a concern, resulting in high cost of operation.

“The assay reagent must be stable at ambient temperature; signal generated by the assay should be stable for an adequate period of time to be able to monitor cells over a period of time,” says Dr. Safinia. “Thus, HTS requires the optimisation of HTS assays and protocols. Approximately $200 million could be saved through more productive discovery programs or cell based assay screens that boost clinical success rates.”

With the increase in demand for new drugs, the degree of competition among the drug discovery companies is also intensifying. The initial investment is considerable; however, the scope for new drug target and profit margins is also high.

“There is, therefore, a heightened need for target validation technology to verify the correct target through advances in assay protocols, novel technologies and reliable data analyses,” comments Dr. Safinia. “Identifying the correct drug target through the use of genomics, proteomics and chemical libraries for drug discovery is a critical bottleneck in the pharmaceutical and biotechnology industries.”

There have been tremendous efforts by the pharmaceutical industry to improve cell based screening platforms to expedite target validation as well as for use in preclinical trials. In order to understand the complexity of biological systems and accelerate the hit-to-lead process, recent advances in microfluidic technologies and automation have attracted a lot of attention with promising applications in cell based biosensors and drug screening.

In addition, considerable efforts are being made to improve the science of predicting the toxicology of emerging clinical candidates to reduce the ADME/Tox failure of drug candidates.

If you are interested in a virtual brochure, which provides manufacturers, end users, and other industry participants with an overview of the European cell based assays markets, then send an e-mail to Patrick Cairns, Corporate Communications, at pcairns_pr@frost.com, with your full name, company name, title, telephone number, company e-mail address, company website, city, state and country. Upon receipt of the above information, an overview will be sent to you by e-mail.

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European Cell Based Assays Markets

Roche has entered into an agreement to provide drug compounds for cardiotoxicity testing using a cell-based platform that could play a major role in the preclinical safety evaluation of drugs and newly developed compounds.

The deal aims to detect any drug-induced changes in the electrical activity of the heart, such as prolongation of the QT interval, which could cause faster, slower, or irregular beating.

Cardiotoxicity has been cited as the reason 30 per cent of all drug compounds fail during testing and with this new deal Roche aim to build predictive models of toxicology to reduce this failure rate.

Under the terms of the deal, Roche will supply Cellular Dynamics International two sets of 25 compounds to test on its platform, that uses human cardiomyocytes derived from human embryonic stem cells. Financial terms of the agreement were not released.

“The validation of the company’s platform through this collaboration is the first step in using these cells in routine toxicology testing,” said Chris Kendrick-Parker, CDI’s vice president of business development.

The late detection of cardiotoxic side effects, such as QT prolongation, caused by pharmacological compounds can impede drug discovery and development projects, and consequently increase their cost.

Drug development can take anywhere between 8 to 16 years, and average cost of developing a drug is now around $500m-$800m with the cost expected to hit the $1bn mark within the next four years.

Market analysis firm Frost & Sullivan has estimated the price of failure at $50m-$70m with approximately 90 per cent of clinical candidates failing at development stage

The launch of new drugs with undetected cardiotoxic side effects could have hazardous consequences and could trigger lethal cardiac dysrhythmias in patients. Testing for the potential cardiotoxic side effects of compounds at an early stage of drug development has therefore been the goal of many pharmaceutical and biotechnology companies.

Electrophysiological test systems and cellular-based fluorometric high-throughput assays are now the test of choice for cloned human cardiac ion channels.

When you consider that every drug nowadays has to undergo testing for hERG block and electrophysiological effects, the potential for this market is huge.

According to Frost and Sullivan, a better understanding of pharmacokinetic properties motivates the use of innovative solutions and early ADME/Tox screening. As a result the European ADME/Tox technologies market is expected to grow from its current size of $384m to $776m by 2011.

Federal scientists are collaborating on a new approach to testing the toxicity of chemicals ranging from pesticides to household cleaners. They plan to use new automated high-speed cell tests to get more reliable data faster and more cheaply, and with less reliance on animal testing.

The National Institutes of Health and the U.S. Environmental Protection Agency are partners in the plan. NIH director Elias Zerhouni says scientists will apply technology developed by the two agencies to identify chemicals that might be harmful to humans.

“You could, in a battery of tests, end up with very specific molecular signatures that will be predictive of human toxicology, in ways that you just can’t do in animal testing today,” he said.

Scientists now rely heavily on animal tests to generate chemical toxicity data. That process is expensive, time-consuming and not always the best predictor of effects on humans says Francis Collins, director of the NIH National Human Genome Research Institute.

“There are differences between species. We are not rats and we are not even other primates, and so that [the] desire here is to see if we could do better,” she said. “Ultimately what you are looking for is [whether] this compound does damage to cells.”

The high-speed automated screening looks at the effects of chemical compounds on single human cells rather than on an entire laboratory animal. Researchers expect the new toxicology testing method will expand the number of chemicals tested and reduce the time, money and use of animals. NIH director Elias Zerhouni says it will also generate data more relevant to humans.

“What is being proposed here is to move the 20th century paradigm of testing of one compound at a time in many animals to going to the 21st Century paradigm [that] tests 5,000 to 10,000 compounds against 20,000 conditions in cells that are very specific to human toxicology,” he said.

Since NIH started the National Toxicology Program 30 years ago, it has tested 2,500 chemicals. Using the new automated strategy could get the same job done in a single afternoon.

John Butcher, associate director of the National Toxicology Program, explains that to check the reliability of this approach, scientists will first do a comparative analysis of the 2,500 chemicals previously tested on animals.

“And we can compare the output from these cell-based assays, in terms of whether these chemicals cause cancer, reproductive and developmental effects, neurological effects, immunotoxic effects and various other kinds of toxicity,” he said.

Butcher says the anticipated shift away from animal testing could take many years. Writing in Science Magazine, he says the agencies expect broader participation from public and private partners in the scientific community as the cell-based testing methods are refined and accepted.

Madison, Wis. - Promega Corp., a provider of life science solutions, has formed an agreement with San Francisco-based Multispan Inc. to co-develop tools for the drug-related screening of protein receptors.

The agreement will team Promega’s line of bioluminescent technologies with Multispan’s line of G-protein coupled receptors (GPCRs) to increase the efficiency of testing for drugs that work on the receptors.
GPCRs, which transmit chemical signals into multiple types of cells, are involved in processes like the regulation of mood, the nervous system, and the immune system. They are among the most widely targeted receptors by pharmaceutical companies.

Promega’s bioluminescent technologies typically are used to study drug targets such as protein and nuclear hormone receptors. The technology also profiles small molecule compounds and assesses the viability and toxicity of various drugs on those targets.

John Watson, marketing director of pharma/biotech at Promega, said in a release that the agreement will provide solutions for scientists researching new drugs, reducing the assay development time on these drugs from months to days.

Research conducted at Birmingham’s Southern Research Institute helped develop a system to identify drugs with the ability to fight the virus that causes AIDS.

Trana Discovery, a North Carolina-based drug discovery technology company, worked with Southern Research to create a screening system to identify drugs that inhibit HIV replication.

The system can be used by pharmaceutical companies to “rapidly and efficiently screen vast libraries of compounds” to help in the treatment of AIDS patients, said Trana CEO Steve Peterson.

Scientists at Royal Holloway, University of London have joined forces with CABI to establish a facility to screen for potential new antibiotics. The aim of the project is to build a highly focused natural products drug discovery operation that will address the urgent need for bringing new antibiotic compounds to market.

Since their discovery, antibiotics and other antimicrobial agents have saved millions of lives and significantly eased patients’ suffering. However, over time, micro-organisms have developed resistance to existing antibiotics making infections difficult, if not impossible, to treat. The recent appearance of multiple-resistant bacterial infections has radically increased the necessity for new antibiotic discovery.

As part of a three-year programme, the joint research facility will utilise CABI’s unique collection of fungi gathered from all parts of the world, to screen for potential new antibiotics. Although the first natural product antibiotic to be used clinically, penicillin, was isolated from a fungus, these organisms have not been as extensively evaluated as bacteria as sources of new drugs for treating infections and so there is great potential for discovery in CABI’s 28,000 organism collection.

Furthermore, over the past 25 years companies have concentrated on using chemistry-based approaches to modify recognised antibiotic structures. However, the use of natural products, from fungi, which have evolved from millions of years of competition against bacteria is likely to lead to products with new modes of antibiotic action that disease-causing bacteria cannot counter. This new joint facility aims to harness these natural chemical compounds from fungi to offer potential new antibiotics. Similarly, compounds that have proven health benefits when taken in the diet (so-called nutraceuticals) are also likely to be found in fungi and the new joint research facility will also screen the collection for new nutraceuticals.

Professor Peter Bramley and Dr Paul Fraser in the School of Biological Sciences at Royal Holloway and Dr Trevor Nicholls, CEO and Dr Joan Kelley Executive Director of CABI are managing the project. Professor Bramley and Dr Fraser’s extensive experience in molecular biology and analytical methodologies will be applied to state-of-the-art screening techniques for the discovery of new compounds and the manipulation, recombination and expression of their biosynthetic pathways to bioengineer new, related compounds. Dr Nicholls’ experience in the biotechnology industry and Dr Kelley’s expertise and knowledge of mycology and biodiversity will direct the research to identify strains which are likely to be more biochemically diverse and commercially valuable for screening.

Professor Bramley commented, “This joint initiative lays the foundations for a long term collaboration with potential strategic benefits, both research and commercial. A major focus will be the search for new antibiotics and nutraceuticals, for which there is now increasing commercial, nutritional and medical demand.”

Dr Trevor Nicholls, CEO CABI added, “This is a really exciting partnership and we are looking forward to working with the expertise of the scientists at Royal Holloway. We are hopeful that our collaboration will prove the winning formula for discovering new drugs to fight cancers, diseases and resistant strains of infections such as MRSA.”

The joint facility is located in the Royal Holloway’s School of Biosciences and houses a new state-of-the-art mass spectrometer. As part of this collaboration, two technicians will be employed and a PhD studentship funded.

Royal Holloway has also obtained early stage seed fund investment from the London Development Agency backed WestFocus PARK Fund, to commercialise any potential new discoveries emerging from this project. The project team will work closely with the Research & Enterprise department at Royal Holloway to protect, manage and exploit any new intellectual property.

About CABI

CABI is a not-for-profit organisation that provides information and applying scientific expertise to solve problems in agriculture and the environment. Its mission and direction is influenced by its 45 member countries who help guide the activities undertaken as a business. These include scientific publishing, projects and consultancy, information for development and mycological services.

Seaside Therapeutics announced today the award of a $4.5 million collaborative research contract to Vanderbilt University Medical Center to discover novel compounds to potentially suppress the manifestations of fragile X syndrome. Fragile X syndrome is the most common inherited disorder of brain development and the most common known genetic cause of autism. Individuals with fragile X can suffer from impaired cognitive function, developmental delay, attention deficit and hyperactivity, anxiety, obsessive-compulsive and autistic behaviors.Research conducted by Seaside founders and others in the field has indicated that excessive signaling through metabotropic glutamate receptor subtype 5 (mGluR5) may be responsible for the neurological and psychiatric consequences of fragile X syndrome. Seaside believes that selective inhibition of this receptor could potentially reduce or eliminate the devastating effects of fragile X syndrome.

Scientists at Vanderbilt, led by Dr. Jeffrey Conn, Director of the Vanderbilt Program in Drug Discovery, principal investigator of the fragile X project and a member of Seaside’s Scientific Advisory Board, have identified more than 400 novel compounds belonging to multiple chemical classes that inhibit mGluR5. With the support of the Seaside Therapeutics’ funding, Vanderbilt researchers will use medicinal chemistry, molecular biology, pharmacology, and efficacy studies to develop compounds that have the properties required for drugs to be used for further study in fragile X. Seaside Therapeutics will collaborate with Vanderbilt on this project by contributing scientific and drug development expertise, particularly as related to fragile X syndrome, autism and other disorders of brain development. Seaside will also select compounds from the collaboration to carry forward into clinical development.

“There are currently no effective treatments for fragile X syndrome,” said Dr. Randall Carpenter, Co-Founder, President and CEO of Seaside Therapeutics. “Seaside believes the best approach to identifying new treatments is to use our own research to discover and validate specific biological sites that play a role in fragile X, and then, either internally or in collaboration with others, develop therapeutics that modulate these biologic targets. We’re excited to work with the team at Vanderbilt given their expertise in drug discovery and, most importantly, because they share Seaside’s passion for helping children with fragile X—creating a strong partnership focused on rapidly translating new discoveries in neurobiology into desperately needed novel treatments.”

“Selectively inhibiting mGluR5 to treat fragile X is an innovative idea and, with continued success, has the potential to change the way people think about developmental disorders,” said Dr. Jeffrey Conn. “While we are at the very earliest stages in the drug discovery process, my team members and I are hopeful we can help advance research efforts in fragile X.”

About Fragile X

Fragile X syndrome is relatively rare, affecting approximately 90,000 people in the United States. It is caused by a mutation in the FMR1 gene on the X chromosome that prevents expression of a single protein, the fragile X mental retardation protein (FMRP). The absence of FMRP gives rise to the major symptoms of fragile X syndrome in humans—impaired cognitive function, developmental delay, attention deficit and hyperactivity, anxiety, obsessive-compulsive and autistic behaviors. A key advance for understanding fragile X was identification of the FMR1 gene and subsequent generation of the Fmr1 knockout mouse—an animal model that lacks FMRP and mimics the human condition. By studying the brain of these mice, Seaside scientific founder Mark Bear, Ph.D., the Picower Professor of Neuroscience at the Massachusetts Institute of Technology’s Picower Center for Learning and Memory, discovered a connection between metabotropic glutamate receptor subtype 5 (mGluR5) signaling and fragile X syndrome. Metabotropic glutamate receptors are activated by the neurotransmitter glutamate. Studies by Bear and others indicate that excessive signaling through mGluR5 may be responsible for the neurologic and psychiatric consequences of fragile X syndrome, and suggest that selective mGluR5 inhibitors will provide therapeutic benefit to this population.

About Seaside Therapeutics

Seaside Therapeutics is creating new drug treatments to correct or improve the course of fragile X syndrome, autism and other disorders of brain development. We are dedicated to translating breakthrough discoveries in genetics and neurobiology into therapeutics that improve the lives of patients and their families.

About Vanderbilt University Medical Center and the Vanderbilt Program in Drug Discovery

Vanderbilt University Medical Center is a major referral center for the Southeast and nation. It is made up of Vanderbilt University Hospital, The Vanderbilt Clinic, The Monroe Carell Jr. Children’s Hospital at Vanderbilt, Vanderbilt School of Medicine and Vanderbilt School of Nursing. VUMC is the largest private employer in the region, employing more than 10,000 employees and generating an annual regional economic impact of over $1 billion.

The primary mission of the Vanderbilt Program in Drug Discovery is to facilitate the application of chemical and other technologies to answer fundamental questions in the biological sciences that may ultimately lead to the development of novel therapeutic strategies. Vanderbilt scientists led by Dr. Jeffrey Conn, Director of the Vanderbilt Program in Drug Discovery, have pioneered the discovery of “allosteric” compounds that modulate (“turn up” or “turn down”) the activation of certain receptors, called metabotropic glutamate receptors, when the neurotransmitter glutamate binds to them. Using Vanderbilt’s high-throughput screening facility, which is capable of testing tens of thousands of small molecules for drug-like activity in a single day, Dr. Conn and his colleagues have identified more than 400 compounds with mGluR5 inhibitory effects.

In Quest for a Cure, Peter Day reports on whether the US Food and Drug Administration will licence the HIV/AIDS drug Maraviroc.

Maraviroc, a new HIV/AIDS drug was developed by Pfizer - the world’s largest pharmaceutical company - at its vast research and development center located at Sandwich in Kent, on the southeastern tip of England.

In the first two episodes (broadcast last year), the series examined how the drug was discovered - by screening millions of compounds in search of just one with the right efficacy and tested at vast cost, on thousands of volunteers.

In the final episode, the story reaches a climax with the public hearing into maraviroc organised by the US Food and Drug Administration in Washington DC in April this year.

At this extraordinary event, a panel of independent experts hear evidence for and against the drug in question. At the end of the day the panel vote, in public. For the Pfizer scientists it was the climax of years and years of work, involving thousands of people and millions of dollars.

When the result was announced - a unanimous yes vote - the team watching on CCTV back in Sandwich cheered and clapped ; some even shed a tear or two. As one researcher remarked “this doesn’t happen very often…”

The next step should have been a formality, with the expectation that the FDA would ratify the panel’s recommendation a few weeks later, but - surprisingly - it did not.

It seems even tumour cells can get lonely; scientists have discovered that by cutting off a key gene, lung cancer tumour cells are left ‘homeless’ and they can’t survive on their own.
The gene in question is called 14-3-3zeta and it can now be considered a potential target for selective anticancer drugs, according to Professor Haian Fu at the Emory University School of Medicine. These latest research results were published in the 24 December edition of the Proceedings of the National Academy of Sciences (PNAS).

Lung cancer kills more Americans annually than any other type of cancer, according to the National Cancer Institute. Yet treatment options are very limited.

“The recent trend towards targeted therapies requires us to understand the altered signalling pathways in the cell that allow cancer to develop,” said Prof. Fu.

“If you think about genes that are deregulated in cancer as drivers or passengers, we want to find the drivers and then, aim for these drivers during drug discovery.”

Prof. Fu and his collaborator, Dr Fadlo Khuri, deputy director of clinical and translational research at Emory Winship Cancer Institute, chose to focus on the gene 14-3-3zeta because it is activated in many lung tumours. In addition, recent research elsewhere shows that lung cancer patients are less likely to survive if the gene is on overdrive in their tumours, Dr. Fu explained.

There are seven 14-3-3 genes, each designated with a Greek letter. Their protein products act as adaptors that can clamp onto other proteins, depending on whether the target protein has been phosphorylated or not. One of the pathways 14-3-3 helps control is epidermal growth factor receptor (EGFR) signalling, which drives the growth of lung cancer.

The team of scientists, including lead author Dr Zenggang Li, used RNA interference (RNAi) to selectively silence the 14-3-3zeta gene. They found that when 14-3-3zeta is turned off, lung cancer cells become less able to form new tumour colonies in a laboratory test.

One of the most important properties of cancer cells is their ability to grow and survive without touching other cells or the polymers that connect them. The researchers found that if they turned 14-3-3zeta off, the tumour cells once again become vulnerable to anoikis (Greek for homelessness), a form of cell death that occurs when cells that are accustomed to growing in layers find themselves alone.

“You can see how control of anoikis means 14-3-3zeta could play a critical role in cancer invasion and metastasis,” Dr. Fu says. “The mechanistic question we still haven’t answered is: what makes zeta unique so that it can’t be replaced by the others.”

Further experiments also showed that 14-3-3zeta regulates the Bcl2 protein family, which is a popular target for cancer drug developers thanks to its role in cell death. If 14-3-3zeta is absent, it upsets the balance within the Bcl2 family.

The finding has implications beyond lung cancer, in that 14-3-3zeta is also activated in other forms of cancer such as breast and oral, he notes.

“Targeting this critical molecule could lead to meaningful therapeutic progress,” said Dr Khuri.

Dr Fu and his co-workers are using a robot-driven screening programme at the Emory Chemical Biology Discovery Center to sort through thousands of chemicals that may disrupt its interactions specifically. They hope to identify these compounds rapidly and move them from bench into clinic testing to benefit patients.

Patients with FDA-defined Valvulopathy Permitted to Enroll in 2nd and 3rd Pivotal Trials - Echocardiogram Screening Requirement Eliminated

SAN DIEGO, Dec. 13 /PRNewswire-FirstCall/ — Arena Pharmaceuticals, Inc. today announced the initiation of patient screening in the second and third Phase 3 pivotal trials evaluating the efficacy and safety of its lead drug candidate, lorcaserin hydrochloride, for weight management in overweight and obese patients. Known as BLOSSOM (Behavioral modification and Lorcaserin Second Study for Obesity Management) and BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus), these one-year, double-blind, randomized and placebo-controlled trials are expected to collectively enroll approximately 3,750 overweight and obese patients. Consistent with Arena’s proposal, the Food and Drug Administration, or FDA, is allowing patients with FDA-defined valvulopathy to enroll in both BLOSSOM and BLOOM-DM. This is different from the design of the initial lorcaserin pivotal study known as BLOOM, in which echocardiography was used to screen for patients with FDA-defined valvulopathy and exclude those patients from enrolling in the trial. Instead, in BLOSSOM and BLOOM-DM, there are no such echocardiographically defined exclusion criteria, although serial echocardiograms will be obtained to extend the lorcaserin safety database. BLOOM, BLOSSOM and BLOOM-DM comprise the entire planned pivotal trial program for lorcaserin.

“Eliminating the requirement of screening echoes, and receiving permission from the FDA to expand the patient population of the lorcaserin pivotal trial program to include patients with FDA-defined valvulopathy, is a significant and positive variation in the protocol for the second two pivotal trials,” commented Steven R. Smith, M.D., principal investigator in the study and Professor at the Pennington Biomedical Research Center. “This change will allow the pivotal trial program to more fully explore, and develop a more complete understanding of, lorcaserin’s selective mechanism and its safety profile.”

“Given the prevalence and impact of obesity, patients and their physicians need new treatment options,” commented Lee M. Kaplan, M.D., Ph.D., an investigator in the BLOOM, BLOOM-DM and BLOSSOM pivotal trials, Director of the Massachusetts General Hospital Weight Center and Associate Professor of Medicine at Harvard Medical School. “Including a broader representation of overweight patients and patients with obesity as part of the pivotal trial program for lorcaserin, including individuals with more significant valvulopathy and type 2 diabetes, is important for providing a more complete assessment of the safety and efficacy of this agent,” concluded Dr. Kaplan.

The BLOSSOM trial will evaluate 10 mg and 20 mg daily doses (10 mg dosed once or twice daily) of lorcaserin versus placebo over a one-year treatment period in obese patients (Body Mass Index, or BMI, 30 to 45) with or without co-morbid conditions and overweight patients (BMI 27 to 29.9) with at least one co-morbid condition at about 100 sites in the United States. The BLOOM-DM trial will evaluate 10 mg and 20 mg daily doses of lorcaserin versus placebo over a one-year treatment period in obese and overweight patients with type 2 diabetes mellitus at about 45 sites in the United States.

Consistent with the BLOOM trial, diet and exercise will also be included in the BLOSSOM and BLOOM-DM trials in accordance with current FDA guidelines, and the proportion of patients with a 5% or greater weight reduction from baseline at week 52 will be the primary efficacy endpoint. Secondary endpoints include changes in serum lipids and HbA1c and, in the BLOOM-DM trial, other indicators of glycemic control will also be evaluated. In both of these additional studies, all patients will receive echocardiograms at baseline, at month 6, and at the end of the study to assess heart valve function over time. In contrast to the ongoing BLOOM trial, however, there will be no independent monitoring by an Echocardiographic Safety Monitoring Board. The complete lorcaserin Phase 3 pivotal program is planned to enroll a total of approximately 7,000 patients in these three trials. In addition to the planned pivotal trial program, several additional small studies, such as drug interaction and abuse potential studies, will be conducted.

“As we continue advancing our lorcaserin clinical program, we are looking forward to March 2008 when we expect the BLOOM Echocardiographic Safety Monitoring Board’s review of echocardiograms for patients completing 12 months of treatment. We will continue to work with the FDA as we implement the final non-pivotal trial elements of the complete Phase 3 program,” stated William R. Shanahan, M.D., Arena’s Vice President and Chief Medical Officer.

An earlier estimate of the total external clinical costs of the Phase 3 trial program was updated from approximately $125 million to approximately $160 million. The increased estimate is primarily due to the increased number of patients Arena plans to enroll, and to Arena’s initiative to expand the echocardiographic monitoring program by including patients with FDA-defined valvulopathy in the BLOSSOM and BLOOM-DM trials.