that the single 8-day course of the Tolerx drug could suppress the over-active T effector cells, and essentially give the T regs a chance to recover their normal state of balance and hold the T-effectors in check over time, Ringler says. If that could be done, it could greatly improve patients’ quality of life by reducing their dependence on insulin and preventing a whole array of painful and debilitating long-term complications that stem from diabetes, like heart attack, stroke, blindness, and limb amputations.
Measuring that sort of benefit is no easy task for anybody, much less a startup biotech company. That’s part of what makes the Defend-1 trial so interesting. While most new diabetes drugs are judged on their ability to control hemoglobin A1C, a standard marker of blood sugar control, that’s not the main goal of Defend-1. Instead, the primary goal of the study is show improvement in levels of biomarker in the blood known as C-peptide, which indicates how much insulin the body is producing. After 12 months, the goal is to show that patients on the Tolerx drug are producing more of their own insulin than patients on a placebo. Researchers will also look at secondary goals like whether patients can get by on less insulin, and how they are performing on their hemoglobin A1C scores.
Since the study design is unusual, it took some time for key research leaders, Tolerx, and the FDA to agree that C-peptide was the right measurement for a pivotal study of the Tolerx drug. Its choice was based on published studies that suggest if diabetes patients can maintain some ability to produce their own insulin, even if just for a few years, it will provide a significant long-term benefit by decreasing their risk of heart attack, stroke, blindness, and so forth.
In an ideal world, Tolerx might run a study that lasts 10 or 15 years to absolutely prove that theory, but it’s already spent a decade and $150 million getting to this point. It can’t afford to wait another 10 years, especially if it has what can be considered a reliable early indicator that those benefits will make this drug worthwhile for patients—and for insurers who want to avoid the high long-term costs of treating them.
“If you can delay symptoms for five years, that provides a huge pharmacoeconomic advantage,” Ringler says. “We don’t need to ask that question over the next five to 10 years.”
Still, Tolerx’s plan to reach the U.S. market will rely on more
