Abstracts

Recent regulatory ICH E14 revisions regarding QT assessment and its impact on Thorough QT studies

Presented by Borje Darpo, MD, PhD, Chief Scientific Officer, iCardiac

Assessing cardiac safety much earlier in the drug development process by using data collected from routine Phase I studies and what iCardiac calls an Early Precision QT approach leads to more precise, cost-effective cardiac safety assessment and informed decision making, which provides significant benefits to drug developers by the means of a more thorough QT study.

In this session, Dr. Darpo will discuss the use of exposure response analysis and High Precision QT measurement technology in the design of more efficient QT studies. He will share his experience from recently performed studies using exposure response analysis for QT assessment, and will talk about the Method Bias Sensitivity metric, which significantly minimizes the possibility of a false negative result.

How innovative technology has transformed Thorough QT studies over the last decade

Presented by Graham Wood, PhD, Executive Vice President, Phase I Clinical Development, Altasciences

Thorough QT studies are complex and challenging, QT prolongation studies being one of the most common reasons for the withdrawal of drugs from the market. Since the release of the ICH E14 Q&A in 2015, a lot of the focus on QT prolongation studies has been on the possibility of being granted a waiver from completing a thorough QT study based on concentration-response analysis; however, for a variety of reasons, such as short-term costs and lack of knowledge of the therapeutic dose early in development, many sponsors are choosing not to add concentration-response analysis to their early clinical trials, which leads to a continuing market demand for thorough QT prolongation studies.

This presentation will outline how novel technologies, such as High Precision QT, have led to more efficient TQT studies over time and how they can be leveraged to deliver more cost-effective and time-efficient clinical trials.

Cardiovascular toxicity evaluation in oncology clinical development

Presented by Gregory K. Reid, MSc, MBA, Director, Medical Science Liaison, Altasciences

Therapies for oncology have been known to cause cardiovascular toxicities, often by affecting cardiac tissue after exposure. Historically, anthracyclines and cyclophosphamide are well-known examples of classes of drugs that require cardiac surveillance and, in the case of anthracyclines and their analogs, there are established cumulative doses permitted for treatment regimens. Newer targeted therapies have also been known to affect cardiac function, but the risk-benefit ratio has been considered positive, given the disease. In this context, regulatory agencies have evaluated to what extent developers are required to study cardiac toxicities as part of the clinical development of new oncology therapies.

The requirements for cardiac evaluation requested as part of a marketing authorization application in oncology will be discussed.