On, February 15, 2018, FDA issued guidance on Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment. The guidance addresses clinical development programs for drugs intended to treat Duchenne Muscular Dystrophy (DMD) and related dystrophinopathies, including Becker muscular dystrophy (BMD), DMD-associated dilated cardiomyopathy (DCM), and symptomatic carrier states in females. The guidance does not address developing drugs to treat secondary complications of muscle degeneration in dystrophinopathies.

Dystrophinopathies affect children and adults and the symptoms range from life-threating and severely debilitating to none at all. Thus, the guidance stresses that drug developers and patients understand safety and efficacy expectations. For example, in addition to informed consent, emerging safety information must be communicated rapidly to study patients and their caregivers so they may reassess continued participation.

The guidance discourages unnecessarily excluding patients from enrollment based on certain characteristics unless scientifically justified. At the same time, the guidance recognizes that a sponsor can target drug development to an identified disease subgroup (e.g., specific dystrophin mutation) and thus base enrollment on a subset of patients in whom clinical benefit is likely to occur.

The guidance notes that FDA will consider the nature of DMD and other severe dystrophinopathies when determining the number and duration of patient exposures needed to support approval, but safety data from a reasonable number of patients exposed to the drug for at least 1 year is generally appropriate.

Regarding efficacy endpoints, FDA provides no defined set of required or recommended clinical outcomes. FDA encourages drug developers to propose and, if necessary, develop endpoints that can validly and reliably assess patients with a wide spectrum of symptoms and disease stages. Developers should show efficacy for a period of at least 3 months for drugs that will be chronically administered. FDA also recommends use of biomarkers that reliably reflect the health and amount of skeletal muscle at a biochemical, cellular, or tissue level as surrogate endpoints to support accelerated approval.

FDA recognizes that many patients affected by dystrophinopathies face a serious and life-threatening disease for which treatments are inadequate or nonexistent. Thus, FDA notes it may be appropriate to permit clinical trials on less than usual nonclinical testing if scientifically justified, and that the typical array of clinical pharmacology testing is likely not needed to support a new drug’s approval.