Cardiac safety issues are among the most common reasons for promising drugs to be halted in development and failing to launch. But, recent regulatory changes are making it easier – and less expensive – for sponsors to confidently determine the cardiac safety profile of their drug candidates earlier in development.
Here, we ask ERT’s Executive Vice President of Cardiac Safety, Alex Zapesochny, five questions about the need for early phase cardiac safety testing and what benefits clinical trial sponsors can derive from it.
1. Why do sponsors need better options for cardiac safety assessment?
Traditional approaches to cardiac safety assessment have a high incidence of inconclusive or positive / false positive results, which can lead to a safe drug being mistakenly 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. How has cardiac safety testing evolved? What are the key regulatory changes?
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 II or early in Phase III. This means that definitive information about a drug’s cardiac liability isn’t known until quite some time into the clinical development process.
At the end of 2015, a revision adopted by 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 Phase I studies. 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 is a pretty significant development.
3. What value does early QT assessment provide?
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.
Accessing better cardiac safety information earlier allows pharmaceutical companies to:
- Make informed go / no go drug development decisions
- Prioritize and package clinical programs with strong safety profiles
- Appropriately resource or refocus programs exhibiting potential cardiac safety issues.
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.
4. What tools are available to ensure sponsors get the highest quality early phase cardiac safety data?
Lack of precision is among the leading causes of inconclusive results in cardiac safety assessment. ERT offers cardiac safety assessment in Phase I studies using Expert Precision QT (EPQT), an integrated ECG analysis platform that improves precision and delivers highly precise data.
EPQT integrates the innovative and broadly-validated analysis methodology for obtaining highly precise ECG data originally developed by iCardiac Technologies (acquired by ERT in late 2017) with the EXPERT® technology platform, which powers all of ERT’s solutions. Pharma companies can also leverage data reliability metrics through a Method Bias Sensitivity (MBS) analysis and enable dose escalation and other time-sensitive decisions via an expedited Agile Statistical Reporting (ASR) service. These offerings are delivered by in-house statisticians who are part of ERT’s Phase 1 Center of Excellence, which we launched in early February.
Using EPQT in cardiac safety assessment strategies will prove especially helpful for smaller biotechs and startups that lack resources to take their compound to the next phase of development. Accessing reliable cardiac safety information on a drug candidate early will help these companies work with partners or investors to bring new therapies to market.
5. What do you hope to achieve in your new role at ERT?
My mission today continues as it has been for nearly 15 years: To help pharmaceutical companies develop safe and effective treatments for the patients who need them.
We accomplish this by developing and implementing the best technologies and practices so that cardiac risks can be identified early and accurately, and so that effective assessment of ECGs can maximize the likelihood of correct inclusion/exclusion decisions and ensure optimal patient safety in clinical trials.
iCardiac was on a path to achieve this mission, but now that we’re part of ERT, we’re able to significantly accelerate and scale our ability to deliver on this goal. I’m proud of the work we’ve done so far, and look forward to what’s coming next as we develop innovative solutions for more effectively centralizing and assessing ECGs from Phase II and III studies.
Click here for more information on how ERT’s Cardiac Safety experts and EPQT can help your next clinical trial.
Smriti Jacob is the Product Marketing Director at ERT.