Multiple firms collaborate to develop new DDIRC

Elsevier, an information analytics business, is working together with a set of evaluation partners including Boehringer Ingelheim, Eli Lilly, Pierre Fabre, Sanofi, Servier, and others to develop a new drug–drug interaction risk calculator (DDIRC).

The updated DDIRC will aim to help DMPK (Drug Metabolism-Pharmacokinetic) and clinical pharmacology scientists improve patient safety and outcomes and reduce risk during pharmaceutical development.

In Europe, 197,000 deaths per year are attributed to them, while the FDA estimates that over 106,000 people die every year due to adverse drug reactions (ADRs). In the US alone, the cost to the medical care system is an estimated $200 billion per year. One reason for the increase in ADRs is the growth in prescription use—especially among ageing populations where drug–drug interactions (DDIs) are more likely.

As DDIRC is a “mechanistic static” modeling calculator that can be used to predict interactions early on—when information on the drug candidate is limited—through to later stages of drug development. It also allows fast predictions, for quick responses to questions from regulatory bodies or physicians.

Jessica Rehmel, MS, consultant scientist - ADME/investigative drug disposition, Eli Lilly said: "Elsevier’s team has collected the background data, and the DDIRC can potentially help us put that data to work to broadly understand DDI implications. We look forward to quickly evaluating and helping to develop this quantitative risk assessment tool."

This joint project between Elsevier’s PharmaPendium team and a group of leading pharma companies will develop and test a DDIRC that can analyse both internal and external data. It will include additional models that can, for example, assess the risk of transporter-mediated DDIs or better assess the risk of DDI due to polypharmacy, and will deliver accurate, shareable and actionable insights.

Yannick Parmentier, head of the Biopharmaceutical Research Department, Servier, said: “Because patient safety has always been a priority for Servier, we want to make sure that our drugs are optimally co-administered. Predicting pharmacokinetic Drug-Drug Interactions (DDI) with the maximum of relevance, precision and reactivity is therefore essential. It starts by anticipating the risk at the research stage, including it in the decision process, to mastering the benefit risk ratio in development phase, optimising clinical DDI trials as well as following up potential combinations with new drugs appearing on the market in the clinical practice.

“DDIRC is therefore an essential tool in those perspectives and enables rapid responses, hence decisions, on the interaction risks. In addition, because the tool will be used by a large community of users it will allow also to harmonise the way to predict DDI to the benefit of the patient.”

By enabling pharmaceutical companies to upload internal data, combined with the high-quality, public FDA/EMA data available in PharmaPendium, the new DDIRC will feature increased predictive power.

Guenther Kurapkat, senior vice president of Life Science Solutions, Elsevier, said: “The healthcare industry’s ability to treat more and more ailments has enabled people to live longer and more fruitful lives, but with that benefit also comes the grave risk of complications when those drugs interact. Researchers developing drugs need tools that can take their valuable internal data and cross-reference it against what’s available in public regulatory filings to get a broader view into how their drugs may interact with others. That’s why we are developing this new DDIRC alongside pharma companies who will depend on it to ensure that key decisions are made with the most predictive insights.

“For Elsevier, this is another important milestone towards a portfolio which helps the pharmaceutical industry in performing better risk-management. With the power of our new versatile data and analytics platform Entellect, we enable insights across data assets from customers, third-party or any of Elsevier’s content in a very flexible and reusable way.”

PharmaPendium’s updated DDIRC will continue to follow FDA Guidelines for mechanistic static prediction of enzyme-mediated DDI risk and could provide information for other models of DDI prediction, based on evaluation partner feedback and feasibility. The new DDIRC is expected to launch in 2020, leveraging the power of our data and analytics platform.