Developing new treatments in partnership for primary mitochondrial disease: What does industry need from academics, and what do academics need from industry?

Abstract

Developing novel therapeutics for primary mitochondrial disease is likely to require significant academia-industry collaboration. Translational assessments, a tool often used in industry at target validation stage, can highlight disease specific development challenges which requires focused collaborative effort. For PMD, definition of pivotal trial populations and primary endpoints is challenging given lack of clinical precedence, high numbers of subgroups with overlapping symptoms despite common genetics. Disease pathophysiology has not been systematically assessed simultaneously with outcomes in available natural history studies, resulting in a lack of pathophysiology biomarker utilization in clinical trials. Preclinical model systems are available to assist drug development efforts, although these may require better standardization and access. Multistakeholder precompetitive efforts have been used to progress disease pathophysiology biomarker and confirmatory clinical trial endpoint readiness in neurological disease with limited treatment options, such as rare familial Parkinson's disease. This type of approach may be beneficial for PMD therapeutic development, although requires significant funding and time, supported by industry and other funding bodies. Industry expertise on chemistry, data quality and drug development know-how is available to support academic drug development efforts. A combination of industry mindset-reduction of uncertainty to provide an indication statement supportable by evidence-together with academic approach-question-based studies to understand disease mechanisms and patients-has great potential to deliver novel PMD therapeutics.

Free sialic acid storage disorder: Progress and promise

“…While we live in a time of unprecedented opportunities for rare disease research and therapeutics, more than 90% of rare diseases still lack an effective treatment. Long research and development timelines, high development and production costs, and small numbers of patients for each rare disease make industry and academic researchers weigh the cost, time and risks associated with therapy development [20,21]. Recent multidisciplinary efforts successfully overcame scientific, clinical and financial challenges facing the development of new drug treatments, including an effort for the lysosomal storage disorder Niemann Pick Disease Type C [22].…”

“…The small population of FSASD patients has hindered industry from investing in the preclinical and clinical studies necessary to develop therapies [20,21]. Recently, however, multidisciplinary collaborative efforts involving the National Institutes of Health (NIH), academic clinical scientists, and patient advocacy groups have successfully overcome the scientific, clinical and financial challenges facing the development of new drug treatments for similar rare diseases [20,22].…”

Editorial: Mitochondrial medicine special issue

“…This issue of JIMD provides a sampling of the gamut of presentations at this meeting, from fundamental research 1 to addressing practical hurdles in drug development, including how to work with regulatory agencies, 2 what is required by industry to move from an early concept to a licensed medicine, 3 and the critical need to develop reliable noninvasive biomarkers of disease progression 4 and other outcome measures to allow effective evaluation of new compounds 5 . Recent developments in animal models were presented, 6 including high throughput approaches for drug screening 7 .…”