A Measure Of Improvement Needed

By Ben Comer, Chief Editor, Life Science Leader

Are drug developers using the right measurement tools and endpoints to test the safety and efficacy of new drugs? In several important therapeutic areas, established scales and biomarkers are becoming problematic, as researchers and clinicians learn more about diseases and progression and make use of increasingly sophisticated digital measures.

For obesity drugs — an industry growth area (see page 16) with an expanding pipeline — the key eligibility measure for treatment (or rather, eligibility for private insurance coverage) is body mass index, or BMI. In June, however, the American Medical Association (AMA) recognized “historic harm” and “racist exclusion” resulting from the use of BMI, since the measure was created primarily from non-Hispanic white population data. The AMA suggested that physicians use BMI in conjunction with other measures, such as waist circumference and body composition, before making individual treatment decisions.

In diabetes, continuous glucose monitors track blood sugar levels 24/7, producing a “time in range” measurement that is more precise, and more useful to patients and physicians, than the hemoglobin A1C test. Because the A1C test represents a three-month average of blood sugar control, it can’t provide an ongoing, up-to-the-minute cause-and-effect measurement that patients can use to better control glucose levels. As an average measure, A1C can miss dangerously high or low glucose levels.

Clinical measures in psychiatric disorders are notoriously tricky as well, as Dan Karlin, chief medical officer at MindMed, a psychedelic drug developer, reminded me during BIO in June. As a branch of medicine that deals with systemic illness, psychiatry largely operates on disease definitions that are phenomenological, or defined by signs and symptoms, says Karlin. “My argument for the past decade has been that our disease definitions are inadequate because our signs and symptoms are inadequate. If you stack up shakily defined signs and symptoms on top of each other, you end up with a disease definition that doesn’t map to the underlying biology.” Over time, illnesses currently labeled generalized anxiety disorder or major depressive disorder will prove to be, instead, a very large number of rare diseases, Karlin says.

For now, drug developers will use the measurement approaches and disease definitions most likely to satisfy regulators. For MindMed’s Phase 2 trial of MM- 120, a “pharmaceutically optimized” version of LSD, Karlin isn’t taking chances with new measurement tools. “When you’re developing LSD for the treatment of generalized anxiety disorder, you’re not going to bring any novel measures to the FDA,” he says. “We want the rest of our development paradigm to be as boring, familiar, and relatable as possible.”