SCD Trials Should Shift Toward Broader End Points, Real-World Monitoring to Expand Eligiblity: Julie Kanter, MD

Current sickle cell disease (SCD) clinical trial eligibility criteria reduced a 456-patient cohort to just 9.9% who would actually qualify, according to data Julie Kanter, MD, presented at the European Hematology Association (EHA) Congress earlier this month.

In part 1 of an onsite interview with The American Journal of Managed Care^®, Kanter explained that her study, "Current Clinical Trials for New Therapies in Sickle Cell Disease Do Not Adequately Represent the Patient Population," shows new SCD therapies are being developed and tested in only a small fraction of the population they are meant to serve. As a result, she called for more individualized postauthorization monitoring once drugs reach the broader patient population.

Kanter expanded on these limitations in part 2 by highlighting the use of an acute pain crisis, or a vaso-occlusive crisis, as the trial end point driving the most exclusions. Because this end point requires patients to have had a measurable but not excessive number of pain events in the prior year, most patients do not qualify. She added that pain is a problematic end point because it is subjective, lacks a biological definition, and is not consistently measured across countries due to differing pain medication practices.

A second major exclusion factor is hydroxyurea use. Since hydroxyurea is the frontline, best-studied therapy, most patients are on it, but many trials exclude these patients, along with those on chronic transfusion therapy. Combining the pain-event and hydroxyurea criteria leaves only a sliver of patients eligible. As a result, Kanter noted that several open trials are competing for the same small pool of patients.

To address this, she described her "mission" to shift the field toward an end point of pain accompanied by acute organ injury, such as liver injury, kidney injury, or hypoxia, measured using standard labs already used internationally, including in the UK and Nigeria. This approach would include patients regardless of prior pain frequency and would translate more consistently across countries.

She also highlighted a new initiative through the National Alliance of Sickle Cell Centers called SCD CORE, a continuously enrolling external comparator arm, which is a subset of the Globin Regional Network for Data and Discovery, also known as GRNDaD. It uses patients on stable hydroxyurea or transfusion therapy, which Kanter said would reduce the number of patients exposed to placebo in trials.

She concluded by highlighting the growing international interest in this approach among colleagues across the globe at the EHA Congress.

“I think what I’m most excited about is the number of conversations I’ve had about SCD CORE here at EHA,” Kanter said. “I have gotten excitement from colleagues in England, France, and Lebanon, so not just in the US, and I think it has great potential to truly change how we do clinical trials in sickle cell.”