The Evolution of Open-Label Extensions and Rare Disease Studies

When running early development studies, sponsors must consider whether or not to provide open-label, long-term treatment at the end of their randomized, placebo-controlled trial. In the past, sponsors have been hesitant to offer open-label extensions. But with our industry’s increasing focus on patient-centric care, sponsors are now weighing their options to incorporate more patient input into early development, especially when working with promising novel treatments in rare disease studies.

Considering the implications of an open-label extension

Biotechs and pharmaceutical companies have understandably been reluctant for many reasons. Exposing patients to long-term risks with no extenuating benefit has ethical implications and legal issues may arise with any negative outcome. Financially, implementing a longer trial can translate into higher development and drug production costs.

From the clinical development perspective, there are also a number of significant considerations, such as:

• Biases related to patients and investigators being aware of treatment assignment
• Higher expectations about treatment success
• A likely decrease in the number of eligible patients for future registration-directed studies
• Possible conflicts with patients who want to continue on the drug—even after blinded trials show no efficacy and development has been discontinued.

Shifting toward a patient-focused approach in rare disease studies

While the implications of open-label extension can seem intimidating, these risks may be offset by the benefits gained from a patient-centric approach in rare disease drug development.

With limited populations to test, each and every patient in a rare disease study is very valuable. An open-label extension helps maximize the amount of information extracted from each patient and gather crucial data that better informs downstream development.

However, incorporating a patient-focused approach takes more than simply running an open-label extension. Sponsors must consider:

• Early engagement with the patient community
• Fortification of natural history data
• Acceleration of preclinical safety studies
• Early vetting with regulatory agencies
• Robust informed consent development with external input
• Development of a solid long-term plan for data interpretation to provide the reassurance needed to acquire adequate financial support.

As the concept and implementation of patient centricity continues to gain traction, sponsors will need to stay ahead of this shift and carefully balance the need for early access to treatments for rare diseases while protecting patients’ safety and the viability of promising novel treatments.