Clinical trial sponsors need actionable and reliable information about the cardiac safety profiles of their compounds at the earliest possible time in the drug development process. But, even with recent regulatory changes, many continue to wait until Phase 2 or 3 to conduct this important assessment, which adds significant cost and time to their development plans.
Here we present four advantages that early-phase cardiac safety testing delivers to clinical trial sponsors.
1. Definitively characterize QT effect early
The traditional approach to assessing a drug’s effect on ECG parameters involves conducting a costly, stand-alone Thorough QT (TQT) study toward the end of Phase 2 or early in Phase 3. This means that definitive information about a drug’s cardiac liability isn’t known until quite some time into the clinical development process
Additionally, this traditional approach to cardiac safety assessment has a high incidence of inconclusive or positive / false positive results, which can lead to a safe drug mistakenly being labeled as high risk for inducing a cardiac event. Early, more accurate QT studies can eliminate these issues and, as a result, give pharmaceutical companies greater confidence in the safety of their compounds ― and the success of their development programs.
2. Prioritize drug development pipeline
Accessing better cardiac safety information earlier in clinical trials allows pharmaceutical companies to:
- Make informed go / no-go drug development decisions
- Prioritize and package clinical programs with well-defined safety profiles
- Appropriately resource or refocus programs exhibiting potential cardiac safety issues
The bottom line is that early-phase cardiac safety testing enables researchers to invest their resources on potentially viable compounds instead of wasting time continuing to develop compounds that might later prove to be unsafe.
3. Save significant development costs and time
At the end of 2015, the International Conference on Harmonization (ICH) ─ an international forum for regulators to harmonize drug approval practices ─ approved an alternative to the TQT study that relies on ECG data collected during routine Phase1 studies. The ICH E14 revision was based on the conclusions of the IQ-CSRC Prospective Study, which relied on the Early Precision QT methodology developed by iCardiac Technologies (acquired by ERT in 2017). This approach requires intensive, high-quality ECG analysis and the use of exposure response modeling. A sponsor submitting QT data that meets certain defined standards, as described in the ICH revision document, may seek a waiver from having to conduct a TQT study.
This development enables clinical trial sponsors to significantly reduce clinical development costs, as conducting cardiac safety testing during routine Phase 1 trials eliminates millions of dollars of investment, as well as the time and resources required to conduct separate traditional TQT testing later in development.
4. Increase value of compound for partnering or out-licensing decisions
Now that sponsors have an alternative to conducting expensive TQT studies, they’re increasingly discovering multiple other advantages to assessing QT early. These include leveraging this early cardiac safety information in discussions with investors or partners. Doing so can add significant value to their compounds, which ultimately impacts licensing or other business development activities.
Cardiac safety issues are among the most common reasons for promising drugs to be halted in development and failing to launch. Clinical trial sponsors who take advantage of recent regulatory changes and conduct QT assessments during Phase 1 can confidently determine the cardiac safety profile of their drug candidates earlier, which enables them to reap significant advantages, including time and cost savings during development.
Smriti Jacob is a Cardiac Safety Product Marketing Director, ERT