The high cost and uncertain outcomes of developing new drugs has taken a toll on research over the past several years. Few companies can take the hit of investing hundreds of thousands of dollars in research and testing, only to see dangerous side effects emerge during the final stages, human clinical trials.
The pursuit of more accurate, less costly testing methods has led many companies to stem cells, which can be coaxed into developing into cells of human organs such as the heart and liver and provide a more accurate, less expensive process for testing. Researchers have been able to generate cells in the laboratory that reach the gold standard required by the pharmaceutical industry to test drug safety. Now, drug companies are increasingly adopting stem cells for research, for testing the toxicity of drugs and identifying potential new therapies.
“I’d say there have been a lot of advances in past five years, but it’s still in its early days,” said Dr. Steven Minger, chief scientist for cellular sciences, GE Healthcare Life Sciences. “There is still a concern about how good the cells are and how they will react. We’ve gone a long way and have a lot of high-quality data, but pharmaceutical companies still have to decide if this is superior to the method they have been using for 40-50 years.”
Safer, cheaper, better drugs
Standard procedure for decades has been to test new drugs on the organs of animals, such as rabbits. But in many cases, there were no adverse reactions in the animals, so companies proceeded to clinical trials, only to discover then the drug caused side effects on human organs, forcing the company to abandon the drug or launch costly research to find a solution.
Now some new medications are being tested for safety on differentiated cells generated from human pluripotent cell lines, which are stem cells capable of developing into any type of cell or tissue except those that form a placenta or embryo. Not only is there an endless supply of them, but they provide a more consistent basis for testing. “Human cells are much more predictable and predictable certainly lowers risks,” Minger noted. Not to mention saving money; developing a new compound can cost as much as $27 million, he added.
“Companies were spending millions of dollars to fail,” Minger continued, “This [stem cell testing] will make for safer, cheaper, better drugs.” The sooner companies are aware of problems with a drug, the easier it is to address them. “They can bail fast, bail early or get rid of the toxic compounds as quickly as possible,” he said. “And just because a drug comes up bad, doesn’t mean the drug is bad. It gives you more options early. The fact that you have data early means you have time to do something with it. Later on, you don’t what to spend billions to find out the problem.”
Heart and liver cells
Cells currently available for use in testing are heart muscle and liver, which are the organs where 80 percent of drug failures occur, Minger added. Drug companies get the cells from firms such as Sweden’s Takara Bio Europe AB, which produces heart muscle cells and liver cells for drug and biotechnology companies as well as universities. “They allow for early testing on human material; you have quality controlled material from the same source,” said Kristina Runeberg, site head/senior director, business development, for Takara Bio Europe AB. Heart and liver cells were considered most important and developed first, but she expects neural cells to come next, and researchers also are working on beta cells, which are in the pancreas.
The results from stem cell testing so far are convincing companies and regulatory agencies that this is the new best practice. The U.S. Federal Drug Administration (FDA) is expected to require at least some drugs to undergo stem cell testing as part of the approval process in the not so distant future.
“We have huge amounts of data and believe they are superior to animal cells; now through a number of organizations working together with the FDA, there is starting to be a consensus built that stem cells have a huge potential and should be the new standard for how pharmaceutical compounds are assessed on a safety basis,” according to Minger.
Future developments include using stem cells to test for long-term chronic toxicity in certain drugs, which requires keeping the same culture for longer periods of time, Runeberg said. Researchers also are working on new ways to identify hazards and test toxicity, added Minger.
“There are 220 different cell types, and it is theoretically possible to make them all,” Runeberg added. “The field has started with the most important ones. In the future, more and more will be developed and more companies will be commercially involved.”