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Evaluating new endpoints
BOSTON—The U.S. Food and Drug Administration (FDA) releases draft guidance regarding a variety of issues regarding drug development and approval, and one of the latest, “Treatment for Heart Failure: Endpoints for Drug Development Guidance for Industry,” addresses the argument that drugs that positively impact symptoms or physical function can be considered grounds for drug approval, even if they don’t have a similar effect on survival or hospitalization.
To this end, Biofourmis has begun a research partnership with the Yale University-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) to explore the value of turning toward a more patient-centric approach in clinical trials. The Yale-Mayo CERSI is a collaboration between Yale, Mayo Clinic and the FDA. BiovitalsHF, Biofourmis’ mobile platform, will be applied in a study of heart failure patients to determine if patient-centric outcomes—specifically, functional capacity and quality of life—should be considered equally with traditional outcomes such as hospitalization or mortality. The FDA’s Center for Drug Evaluation and Research will be funding the trial.
“Heart failure is a highly prevalent disease that not only carries high morbidity, but also significantly lowers a patient’s quality of life,” Kuldeep Singh Rajput, CEO of Biofourmis, said in a press release. “While hard outcomes such as mortality and hospitalization rates have served as the traditional endpoints in clinical studies, we also should take into consideration the patients’ levels of satisfaction and well-being while being treated with a heart failure drug during a trial. Not only is quality of life important in a disease such as heart failure, but patient-centric endpoints can be identified much more quickly than traditional hard outcomes.”
“Biofourmis is a leader in the emerging field of digital therapeutics, and we are thrilled to be partnering with them on this important study,” commented Dr. Nilay Shah, principal investigator at the Yale University-Mayo Clinic CERSI. “This study will not only advance science, but will also provide insights to the FDA on how these measures can be used as alternative trial endpoints.”
The study in question will begin this month, recruiting recently discharged patients with heart failure. The patients will be screened, then monitored at home for 60 days using Biofourmis’ BiovitalsHF platform. BiovitalsHF collects raw biosensor data and applies advanced machine learning to pinpoint physiological biomarkers. Study participants will be wearing two biosensors: Everion, a medical-grade device, and the Apple Watch Series 4, and will use the BiovitalsHF companion app to sync their data from the sensors. The app will also collect electronic patient-reported outcomes such as medication adherence, symptoms, the Kansas City Cardiomyopathy Questionnaire (KCCQ) responses, and the guided mobile-based 2-minute-step-test.
The study’s goal will be to assess the correlation between physiology and actigraphy biomarkers based on clinical endpoints such as lab results, the KCCQ and the six-minute walk test. A secondary goal, according to Rajput, will be to determine whether consumer-grade wearables such as the Apple Watch can be used as effective surrogates for clinical-grade biosensors.
“If you look at how we measure function clinically today, it’s using your typical six-minute walk test, or stress test, which is expensive; you still have to come to the clinic, you have to wait a couple hours to set it up, and the cost of the trial as well as the duration of the trial increases significantly,” Rajput tells DDNews. “If we can use novel monitoring tools and analytics to be able to quantify other biomarkers, things like activity intensity, position, posture, gait, cadence, which could be surrogate markers to continuously measure these endpoints, that would essentially speed up trials. As well, FDA would be able to define those as the guidelines. Because in the latest guidelines, they made it very clear that more emphasis should be and will be placed on functional capacity rather than looking at mortality or hospitalization.”
It’s thought that switching to or incorporating patient-centric outcomes could accelerate the drug approval process. Since outcomes such as quality of life or functional capacity can be measured more rapidly than hospitalization or mortality, getting a heart failure drug to market could take five to six years if patient-centric outcomes are considered, rather than the current average of seven to eight years. And the time savings will mean cost savings as well.
“When I started Biofourmis, it all revolved around patient centricity, and how can we monitor patients using the right sensors and capture the right data, either actively or passively, and be able to predict decompensation in patients well before they become symptomatic,” says Rajput. “We have built the platform, a system which essentially has three main pillars. The first one is of course a patient-facing component, which includes our device-agnostic platform to capture multivariate physiology data from sensors. We have integrated 20+ FDA-approved technologies onto a platform, and of course recently consumer-grade sensors like Apple watch. The goal there is not to inflict patients with multiple sensors—it’s to have a single sensor which patients wear on their body and forget about it, and we are still able to capture all relevant biomarkers.”
“The second pillar is our analytic engine, which has more than 800 modules,” he continues. “We have shown in multiple studies, one recently done at Mayo, where we could predict heart failure exacerbation 14 days in advance before actual hospitalization, with more than 90 percent sensitivity specificity. Once you have done that, you use our treatment algorithms to optimize therapy, which is essentially titrating medications to ensure that patients have the right dose at the right time, eventually showing better improvement in patient-centric outcomes like functional capacity and quality of life.
“The third pillar is the impact for caregivers, nurses and additional value-added services, which includes DMR-integration, medication delivery directly to the patient.”