Yesterday was World Heart Day, a global event that provides us all with an opportunity to celebrate the incredible progress we’ve made in fighting cardiovascular diseases (CVD) worldwide. Yet it is equally important that we take this opportunity to reflect on the challenges we still face together in discovering and developing new therapies that will lessen its impact on the global population.
Although some have argued that with the novel anticoagulants, PCSK9s, and Entresto entering the space recently, there may be less opportunity for significant innovation in the CVD, I would argue that just the opposite is true. CVD remains the number one killer the world, with 17.3 million deaths per year attributed to CVD, according to the World Heart Federation. To put that number in context, CVD kills more than five times as many people every year as Malaria, HIV/Aids and Tuberculosis combined.
The numbers speak for themselves: there is dire need for continued urgent research in this space, and innovative strategies to get these drugs to market faster and at less cost. One way to do that is to change the way we conduct and measure the value of Phase I studies.
The Phase I Patient
In many drug development programs that we see, sponsors often use only healthy subjects in their Phase I trials to measure safety, tolerability, and pharmacokinetics of their new compounds. Although this is a well-established approach, we believe they may be missing an excellent opportunity to gain patient and disease insights earlier in the development process. While in many cases, single-dose studies in healthy subjects may be prudent for initial profiling, addition of patients to these trials not only offers the opportunity to confirm the profile in the target population, but also gain early insights into the likely efficacy of the compound if appropriate pharmacodynamic and disease-related biomarkers are available or in need of testing.
With this relatively straightforward adjustment, researchers would generate more value earlier in the process – for themselves, for sponsors of drug trials, and especially for their patients – by turning this Phase I model on its head. Such an approach offers many short and long term benefits:
- It offers testing in subjects more likely to derive benefit from it. Healthy volunteers receive no real benefit for participating in a Phase I drug trial, beyond compensation for their time and free health checks. By bringing actual patients into this phase, researchers increase the opportunity to help the at-risk population sooner in the development process. And it allows sponsors to confirm the drug profile in the target patient population sooner.
- It spurs recruiting efforts. By including patients in development trials right from the beginning, sponsors and Investigators will have more time to meaningfully learn from the patient community and develop more effective methods, such as, registry building, patient reported outcomes tools, and patient advocacy support, for establishing more sustainable relationships with patients and their families. This will both promote better patient participation in clinical trials and build a concrete pool of likely subjects for current and future studies. Community building is essential for sustainable success in patient recruitment, especially considering the years-long duration and thousands of patients required in many CVD development programs.
- It helps researchers hone their recruiting protocols. By working with patients from the outset, researchers can use that early sampling opportunities to test their hypotheses about the right candidates for their drug, the right biomarkers and other end points for the trials, and the right inclusion/exclusion criteria to increase the chance of success for future related trials.
- It speeds collection of valuable data. The sooner patients are involved in research, the more information researchers can collect about their responses to the drug and the dosages that have the biggest impact on their condition – none of which is possible when using healthy subjects. The data collected from patients in Phase I trials can be used to inform future decisions, cut valuable time from later stage research, and shorten the path to treating patients. In some cases, researchers may choose to combine Phase I and IIA studies, achieving proof of concept much earlier and accelerating the move directly to phase IIB and III studies..
- It increases the commercial viability of the drug. If done smartly and carefully, involving patients earlier in drug development has the potential to cut a significant amount of time off of the typical CVD drug development timeline, which gives sponsors more time to market their novel therapies during the period of patent exclusivity.
We hope that sponsors and investigators consider earlier patient participation in Phase I trials because it is never too early for patients to make valuable and much needed contributions to healthcare innovation. By working with patients sooner, the CVD research community can increase the chance of helping individual patients and the global population of CVD sufferers, by more efficiently bringing drugs to market that will both save lives and bring commercial success to the companies that create them.