New Guidance on DMD per waterloo0119 Feb 2018 10:20
New guidance out from FDA re DMD. It does demonstrate a more flexible approach including use of novel biomarkers and some alternatives to some of the function tests
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM450229.pdf
In dystrophinopathies, biomarkers that reliably reflect the health and amount of skeletal muscle
at a biochemical, cellular, or tissue level may be useful across the drug development process,
17 - See the draft guidance for industry Adaptive Design Clinical Trials for Drugs and Biologics. When final, this
guidance will represent the FDA�s current thinking on this topic.
Contains Nonbinding Recommendations
11 - including use as prognostic, predictive, or pharmacodynamic markers, or, in some instances if
supported by sufficient scientific evidence and acceptable analytical methods, as surrogate
endpoints to support accelerated approval. A single biomarker measure can, in different
circumstances, serve different functions; for example, baseline dystrophin expression can be a
marker of a patient�s prognosis whereas an increase in dystrophin could reflect biological
activity of a drug and guide key aspects of drug development such as dose selection and route of
administration. Even if it cannot be concluded that a given biomarker can serve as a surrogate
endpoint, positive findings based on a biomarker may help support the mechanism of action of a
drug, help identify the appropriate patient population to study or treat, or support the validity of
findings on other endpoints. To support continued progress in overall drug development for
dystrophinopathies, trials with clinically meaningful endpoints should include a selection of
relevant biomarkers to help establish the correlation between such biomarkers and clinical
endpoints.
The potential for a biomarker to predict clinical benefit in dystrophinopathies could relate to the
magnitude of change of the biomarker and tissue in which the biomarker is measured. The
meaning of a change in a biomarker might also depend on the age or disease stage of a patient or
on other patient factors such as inflammation or autoimmunity to dystrophin or other muscle
components. When biomarkers are assessed, analytical validity should be demonstrated to the
extent possible, and there should be adequate assessment of the performance characteristics of
the biomarker assay, including quality-control measures and documentation of results.
Deficiency of functional dystrophin appears to be the proximate cause of the symptomatic and
functional consequences of dystrophinopathies, justifying particular interest in dystrophin as a
biomarker and as a potential surrogate endpoint for accelerated approval.
FDA also encourages sponsors to consider the use of other biomarkers, such as those measured
with magnetic resonance imaging or magnetic resonance spectroscopy. Advantages of imaging
include its noninvasiveness, its ability to
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