Patient preferences and biomarkers in drug development

Patient preferences and biomarkers in drug development

Posted on April 20th, 2022

A SPARK research study recently published in the Journal of Clinical and Translational Science highlights the importance of including patient preferences in the development and approval of preventative therapeutics.

SPARK co-director Kevin Grimes and former SPARK postdoctoral scholar Marcus Parrish led a study to identify the preferences of individuals at risk of developing Huntington’s disease regarding the use of biomarkers such as brain imaging and protein levels in the blood and spinal fluid for FDA approval of preventative therapeutics. In 2020, FDA published a guidance document on Patient-Focused Drug Development intending to include patient preferences and experiences in development of disease therapies. In this study, the team asked members of the HD community to complete a survey investigating their willingness to take hypothetical preventative therapies with various side effects and different levels of improvement in HD biomarkers.

Huntington’s disease is a genetic, progressive neurodegenerative disorder that generally manifests during middle age or later. Since at-risk patients can be identified through genetic testing many years prior to symptomatic disease, treatments might be initiated that can delay or prevent the onset of symptoms. Biomarkers that appear to correlate with disease activity include regional brain atrophy on MRI scans, elevated mutant huntingtin protein levels, and increased levels of proteins reflecting neuronal damage and inflammation. These biomarkers show progressive changes many years before symptoms occur. A drug that prevents deterioration of these biomarkers may also prevent progression of HD.

The survey results showed that the HD community is strongly interested in preventative treatments and is willing to tolerate substantial side effects for potential benefit. When assessing the potential treatment options, the survey respondents put significantly higher weight on biomarker improvement than the risk of potential side effects.

The authors concluded, “These results indicate a strong desire among members of the HD community for preventive therapeutics and a willingness to accept significant side effects, even before the drug has been shown to definitively delay disease onset if the drug improves biomarker evidence of HD progression.” Including these preferences could improve development and approval of preventative therapies for HD.

As the HD community has a strong desire for preventative medications, the study also highlights the importance of biomarker use during drug approvals. “The use of predictive biomarkers as clinical trial endpoints could accelerate the approval and clinical adoption of these drugs,” the authors wrote. 

Dr. Grimes stated, “It is imperative that we give patients a voice regarding how drugs are developed for serious illnesses. In the era of genetic testing, we can now identify patients who are likely to develop serious illnesses many years prior to symptom onset. The FDA Accelerated Approval Program allows earlier approval of drugs that address a serious unmet medical need based upon approval of a surrogate or biomarker endpoint that is thought to predict clinical benefit. The use of predictive biomarkers is particularly well suited to HD since mutation carriers have nearly 100% chance of developing the disease and high-quality studies have contributed to our understanding of disease progression and changes in biomarkers before symptom onset. If we develop a novel clinical and regulatory paradigm for HD preventive therapies, this can serve as a model for developing preventive therapies for other genetic diseases.”