Posts Tagged liver
Posted by Darshana V. Nadkarni, Ph.D. in Biotech - Medical Device - Life Science - Healthcare on January 29, 2013
Dr. Mike Bowles, previously a founder of Com21 and IBeam Broadcasting (both of which went on to huge IPOs) and currently co-founder of Biomatica, talked about the application of Computational Biology to investigate drug toxicity effects, earlier in drug development process. It is an understatement to say that drug development is very expensive, often costing billions of dollars and years of research. The primary challenge is determination of long term drug toxicity side effects. If we can develop and deploy efficient technologies for early prediction of adverse side effects, then the costs of drug development can be noticeably reduced, said Bowles.
However, the toxicity studies often take place relatively late in the process. During first year of research, the focus is on identifying and validating target molecules from over 5000 compounds. Toxicity is not studied until much later in the development process. Liver damage is one of the worst potential side effects of drugs, taken alone or with other medicines. “We need a paradigm shift”, said Bowles, to include toxicity studies earlier in the development process. But animal studies are also time consuming and they leave many uncertainties about human risk potential. Often by the time the animal data is in, too much is invested and it is costly to cancel the compounds. So there is an incentive to go on, rather than to eliminate compounds with riskier profiles.
Biomatica addresses this challenge by replacing liver toxicology studies on live rats with machine learned models of liver damage that can be run on rat (or human) liver cells grown in culture. They have built models using microarray data from hepatocytes to predict animal and human toxicity. Toxicity does not occur through just one pathway and it is a diffused problem. But microarray can encompass all the changes going inside a cell, at any point in time. Microarray data is collected on rat liver or rat hepatocytes grown in cultures or human hepatocytes grown in cultures and used to find earlier the compounds that should be eliminated. Testing costs earlier on live rats and on microarrays are similar. But at following stages they start adding up, in case of live rats. For instance, for 36 rats, in later stage, while they come to about $20,000 with microarry, with live rats they go as high as $113,400. The early results are indicating very good prediction accuracy, said Bowles. The talk generated a lot of interest and was followed by Q&A.
Pierre Cassigneul CEO of XDx (www.xdx.com) discussed how AlloMap is poised to change medical practice and revenue stream at www.bio2devicegroup.org
Posted by Darshana V. Nadkarni, Ph.D. in Biotech - Medical Device - Life Science - Healthcare on March 16, 2012
XDx is a molecular diagnostics company with a focus on discovery, development, and commercialization of noninvasive gene expression testing that would translate a patient’s immune system information to clinically actionable information. The goal is to help in effective monitoring of transplant rejection and autoimmune diseases.
After the transplant, the organ recipient’s immune system recognizes a transplanted organ as foreign, and mounts a response to reject it. Currently, the only standard method to monitor for such rejection is endomyocardial biopsy and then prescribing drugs to suppress the body’s natural immune system response. There are two significant challenges. Endomyocardial biopsy is an invasive procedure that requires puncturing the jugular vein and inserting the guide with fluoroscopic or echocardiographic guidance. The jaws are then opened and a tiny piece of the heart is removed. This invasive procedure is performed weekly during the first month, with gradually reducing frequency to annually after twelve months. Besides being painful and an invasive procedure with potential of many complications, this is also an expensive procedure costing up to $4 to $10 thousand per biopsy. An additional challenge pertains to the determination of the dosage of immunosuppressant drugs. The correct dosage is determined on the basis of the information derived from the biopsies and this is somewhat of a subjective decision, with high consequences. The dose cannot be too high or too low as these drugs are powerful drugs with serious side effects, and frequently lead to renal or liver failure, in the long term.
AlloMap is XDx flagship product to aid in the identification of the probability of acute cellular rejection for post cardiac transplant patient management. This is a noninvasive method to monitor immune system activity by measuring gene expressing in a patient’s peripheral blood. The AlloMap blood test is CLIA certified and reports a score and is therefore a quantitative measure, that takes out the subjectivity from determining the right dose. The hope is also that the patient can then take the lowest possible dose needed. XDx has 30-44 thousand test capacity, annually. Not only is this a highly cost saving method to determine the right dosage, but it is a non-invasive, more humane method that should replace traditional biopsies.
Cassigneul shared results from several studies that indicate AlloMap to be as clinically effective as biopsies. And yet, the company has encountered revenue challenges, payer resisting coverage, hospitals making it more challenging to get the blood drawn and so on. However, recently Society of Heart Lung Transplant, recommended AlloMap in their clinical guidelines. This was a huge milestone for XDx and cleared the path for revenue generation. Now several payers have also recommended AlloMap for coverage. One hundred out of 140 transplant centers in theUS, have used the test and the company is seeing a steady growth. The company is working on several tests for monitoring of other transplant organs and also for monitoring several autoimmune diseases like Lupus, Rheumatoid Arthritis and so on. For Lupus, XDx is working on flare predictor so that sudden flare-ups can be caught prior to irreversible damage to kidneys and other organs. The talk generated strong interest and was followed by Q&A.