Balancing the need for early access to treatments for rare disorders and protecting patients’ safety and the viability of promising novel treatments
Over the past 10 years, I have been asked to provide advice on whether or not to provide open-label, long-term treatment with novel drugs during early development. I had followed the orthodoxy to not offer such treatment until some demonstration of beneficial effect and robust preclinical safety data are generated. However, our understanding of acceptable risk in the context of diseases with high unmet medical need is changing. I recently was involved in such a case in which an open-label extension for a phase 1b study seems to make sense.
Examples of patients’ growing influence are the Patient Focused Drug Development Initiative (PFDDI), created out of the Food and Drug Administration Safety and Innovation Act (FDASIA), which is directed to incorporate patient view point in the regulatory process. Several of the PFDDI 2014 meetings are relevant to my area of expertise, neuroscience: Fibromyalgia (March 26, 2014); Neurological manifestations of inborn errors of metabolism (June 10, 2014); Parkinson’s disease and Huntington’s disease (TBD). Another example is the collaboration between the FDA and the Duchenne Muscular Dystrophy patient community to advance useful regulatory tools for benefit-risk consideration in DMD (page 58). Similar efforts to incorporate patient input for orphan disease are underway in Canada. Formalizing consideration of patients’ preferences will likely have direct implications for determining acceptable risk when benefit is largely unknown and even the regulatory value of the data provided by open-label extension studies.
This shift has significant implications for biotech and pharmaceutical companies in various areas, such as ethical (eg, exposing patients to long-term risks with no extenuating benefit), legal (eg, liability for negative outcomes) and financial (higher drug production costs, implementation of longer trials). For those of us in clinical development there are also a number of significant implications, such as larger placebo effects because of higher expectations about treatment success, a decrease in the number of eligible patients, and conflicts with patients who want to continue on the drug even after blinded trials show no efficacy and development has been discontinued.
So what implications does this change in thinking have for future drug development? It means that compounds and patient populations appropriate for potential early open-label extensions need to do a lot more upfront planning and implementing. For instance:
- Early engagement with the patient community
- Fortification of natural history data
- Acceleration of preclinical safety studies
- Early vetting with Regulatory agencies
- Robust inform 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.
To share your views on open-label extension studies and discuss the risks and benefits of an open-label extension study for your disease indication of interest, please contact us.