This week, Certara, a software and scientific consulting vendor, launched the Cardiac Safety Simulator, a tool that lets pharmaceutical companies test the toxicity of potential drug candidate on the heart using an in silico model of ventricular cells and determine safe dosage regimens prior to launching clinical trials.
Certara launched the CSS in response to a perceived need for tools that enable pharma firms to "understand the mechanistic behavior of drug [candidates] at an early stage" as well as "the implications of genetics, gender, and other covariates on the risk of arrhythmia," James Hayden, Certara's senior vice president of global sales and marketing, told Bioinform. He also said that the company sees the cardiac safety market as a potential growth area for its business.
"Cardiac safety is a major challenge in drug development," he said. "Many drugs have been pulled from the market that exhibit QT prolongation and as a result the industry has begun killing compounds in early development that appear risky." With CSS, drug developers may be able to "save certain drugs that may exhibit QT prolongation by identifying the right dose or patient population in which the drug is safe."
The CSS is integrated with Certara's Simcyp Population-based Simulator — a program used to model pharmacokinetics and pharmacodynamics activities in virtual human populations as well as in virtual laboratory animals. The simulator is part of the assets Certara obtained when it bought Sheffield, UK-based Simcyp last year for $32 million.
According to Sebastian Polak, principal scientist at Certara’s Simcyp and chief architect of the CSS, the model incorporates pharmacokinetic and pharmacodynamic data as well as information about the electrophysiology of heart cells and uses it to predict the likelihood that drug candidates will be toxic to the heart. Researchers can use the model, he said, to "determine whether a drug candidate is likely to cause disruption of the electrical potential in the left ventricular cardiac cells and QT prolongation," both of which are markers of arrhythmias. Furthermore, because the CSS is integrated with the Simcyp population simulator, users can also explore the effect of demographic, physiological, and genetic variables as well as biologic rhythms on drug toxicity.
Polak, who's also an associate professor at the Jagiellonian University in Krakow, Poland, told BioInform that the simulator can be used to rank potential drug candidates being considered for further development and to determine safe dosing levels should the development efforts move forward. It can also be used at later phases of the drug's development process to refine their initial predictions, he said. For example following the first phase of a clinical trial, the simulator could be used to reassess initial drug toxicity predictions based on data collected during the trial.
Certara also said that although CSS’ initial focus is on QT prolongation, there are plans underway to include additional electrophysiology endpoints as well as the ability to simulate heart contractility and heart muscle cell metabolism.
CSS is available only to members of Certara's Simcyp consortium, a group of pharmaceutical firms including Pfizer, GlaxoSmithKline, AstraZeneca, and Eli Lilly as well as the US Food and Drug Administration, which all license the Simcyp simulator for internal use. Members of the consortium pay a fee, which is also the cost of the software license. Pharma companies interested in CSS will have to join the consortium if they want to use the tool, Certara's Hayden said. They will also have to pay a separate undisclosed fee to use the CSS as its cost is not included in the membership, he said.
Besides investing in cardiac safety, Certara plans to focus more effort on other products in its portfolio where it sees growth potential, according to Hayden. This includes its Simcyp business, which he said has grown over 50 percent in the first half of 2013. Other products like D360 as well as some of the PK/PD modeling offerings are also "doing quite well" and Certara will be investing more of its resources in these areas, he said.
The company, which pulls in almost $60 million in revenue, according to Hayden, is also investing resources in linking products from its three subsidiary companies — Tripos, Pharsight, and Simcyp. "For example the Simcyp simulator now links with the Phoenix product line" from Certara subsidiary Pharsight, "so you could run a simulation in Simcyp and then input the data directly into another tool we have called WinNonlin that does the PK/PD modeling," he said.
Certara's customers include the FDA, which is using its Simcyp Dog model to evaluate drug products intended for use in different canine breeds (BI 11/16/2012) and Plexxikon, where scientists are using the D360 software for drug discovery projects (BI 12/7/2012).
Also, earlier this year, Certara signed a partnership agreement with ChemAxon that allows it to provide its customers with access to ChemAxon’s MarvinSketch — a chemical structure sketching tool — and its JChem chemistry data cartridge, through the D360 solution (BI 3/22/2013).