Arresting cardiac risks

ROCHESTER, N.Y.—Pharmaceutical companies may soon have an opportunity to significantly streamline and reduce the cost of developing new drugs. A study recently released by the U.S. Food and Drug Administration (FDA) suggests that a new means of testing drugs for cardiac safety—an FDA requirement—could take place much earlier in the clinical development process than current methods of testing allow. The FDA’s study, conducted in collaboration with iCardiac Technologies and the Cardiac Safety Research Consortium (CSRC), found that iCardiac’s Early Precision QT methodology to analyze ECG data accurately assessed the cardiac safety profiles of five marketed drugs.

This new approach toward detecting a drug’s potential to cause cardiac problems could move cardiac safety testing upstream in the pharmaceutical R&D pipeline, from large and expensive later-phase studies to smaller and earlier first-in-human studies.

“Companies typically spend between $2 million and $5 million on cardiac testing at the end of Phase 2,” Alex Zapesochny, president and CEO of iCardiac Technologies, tells DDNews. “This new method allows a company to spend 5 percent to 10 percent of that amount and have an answer about the drug’s cardiac safety at the very beginning of Phase 1.”

Since 2005, the FDA has required that all new drugs under development undergo rigorous testing to determine their potential for cardiac toxicity. This policy has helped to prevent drugs being introduced to the market that are later shown to contribute to serious heart problems such as arrhythmia and sudden cardiac death. The success of using ECG in human clinical trials to determine cardiac safety has improved overall drug safety and helped pharmaceutical companies avoid withdrawing drugs they have spent large sums developing and marketing.

However, the FDA’s mandate for cardiac testing has also had negative consequences. The added cost of testing has caused pharmaceutical companies to become more reluctant to invest in the development of some drugs. This reluctance has led companies to abandon drugs with profiles similar to those shown to cause heart problems. “The costs of cardiac testing are very high for pharma companies, but the FDA wasn’t motivated to pursue new methods because it was concerned about costs,” says Zapesochny. “What motivated the FDA, and the industry, was concern about companies killing drugs early in their development due to indications of cardiac safety issues.”

The new method of cardiac testing used in the FDA study also offers advantages in terms of precision. The study found that iCardiac’s Early Precision QT testing has a lower than expected incidence of inconclusive results compared with historical assessment methodologies. The method analyzes over 100 times the data of traditional analysis methods, according to iCardiac, allowing for much earlier insights into the viability of drugs in development. “Access to more accurate cardiac safety data early in the clinical trials process can mean accelerating the development of promising drugs that might have been canceled due to inconclusive or inaccurate results from the manual assessment processes currently in use by traditional ECG core laboratories,” says Zapesochny.

The FDA released the results of the study on Dec. 12 at a meeting of the CSRC. The study was funded and managed by iCardiac, and the data produced were handed off for analysis to a third-party statistician and the FDA. Results of the study have been published in the December issue of Clinical Pharmacology and Therapeutics.

The FDA’s role in the study has important implications for companies interested in taking advantage of the new cardiac testing method, Mike Totterman, iCardiac co-founder and chief innovation officer, tells DDNews. “An important question with a development like this is always, ‘what’s the view of the regulator?’ In this case, we collaborated with the FDA and the agency has said it is able and ready to accept data from this method of testing from companies that would like to have their QT study waived.”

If the new methodology is embraced by the industry, iCardiac, a dedicated ECG core laboratory that serves the pharmaceutical industry, stands to benefit enormously. Zapesochny predicts that its proprietary methodology will be a major contributor to the company’s growth. “Since it was our specific methodology used in this validation study, we believe we have a major head start in terms of being the standard bearer for this particular type of approach,” he says. “We have already made inroads with a number of sophisticated clinical sites that want to partner with us on this methodology, and we’ve developed a process of certifying sites that want to run these kinds of tests.”