Today is a historic moment for the Duchenne community, as moments ago the FDA published the finalized “Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment” Guidance for Industry (click here to access), along with four other guidances. According to the FDA, “This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic.”
Today’s publication is the result of years of work from multiple stakeholders in this community, including all of you who contributed your voice, your story to the initial draft guidance PPMD submitted in 2014. Often FDA guidance stays in draft form, but the FDA has made our community a priority and we are hopeful that this final version will provide more clarity and insight into the agency’s approval process. We look forward to diving in and comparing this final version to the draft version the FDA shared in 2015, and we will of course share with you our analysis.
Click here to download the document.
Statement from FDA Commissioner Scott Gottlieb, MD:
New medical breakthroughs are altering how diseases are treated in ways that seemed unimaginable just a decade ago. Perhaps one of the most significant developments is the advent of new gene therapies and drugs that boost the immune system’s ability to target tumor cells. But we recognize that progress across different therapeutic areas has been uneven, including for complex neurological diseases. In part, this is because the underlying causes of severe neurological diseases may not be as well understood compared to ailments like cancer. The brain, in many respects, is the last organ system where many aspects of our understanding of the underlying biology of disease remain uncertain.
Symptoms and progression of neurological diseases can also vary significantly across patients, and even within patients, and across organ systems. Some diseases, like Alzheimer’s, may progress invisibly for years. Once clinical symptoms become apparent, significant function may already be lost. These issues can make drug development more challenging for companies, and are deeply frustrating for patients and caregivers living with these serious and life-threatening conditions.
The FDA recognizes the urgent need for new medical treatments for many serious conditions including neurological disorders such as muscular dystrophies, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), migraine and epilepsy. This requires us to become more nimble, collaborative and patient-focused. As part of our ongoing efforts to expand access to safe and effective treatment options across all disease areas and promote innovation, the FDA is modernizing multiple aspects of our drug regulatory programs – including how we communicate scientific and regulatory guidance for drug development.
To keep pace with science and best meet the needs of the patients we serve, we’re also changing how we organize ourselves as part of the medical product review process – moving away from a more siloed structure that had people working in discrete organizational units. Professionals with particular subject matter expertise often operated as independent entities based on their areas of experience. Instead, we’re moving toward a more team-based approach as part of our Center for Drug Evaluation and Research’s (CDER) Office of New Drugs modernization. Under this team-based approach, experts across different fields will share best practices and knowledge focused on diseases. This approach will integrate people from different disciplines – such as pharmacology and statistics - and across different stages of the life cycle of a product from the pre- and post-market phases who are all working toward a common public health goal.
One area where we’re already putting this new organization to the test is through guidance development. We’re piloting a new, streamlined process for writing science-based, practical guidance documents and getting them out more quickly. Guidances in the pilot are intended to be concise and free of lengthy narratives that didn’t help advance the goals of providing clear scientific feedback. These new guidances should not duplicate information already available in other documents.
Today I’m pleased to issue five guidance documents that benefited from the streamlined approach of this pilot as part of a broader, programmatic focus on advancing treatments for neurological disorders that aren’t adequately addressed by available therapies. These guidance documents provide details on how researchers can best approach drug development for certain neurological conditions – Duchenne muscular dystrophy (DMD) and closely related conditions, migraine, epilepsy, AD and ALS. These guidance documents provide our current thinking and sound regulatory and scientific advice for product developers so that safe and effective treatments can ultimately be made available to patients. These documents are each a culmination of thoughtful scientific collaboration within the agency and incorporate important input from patients, researchers and advocates. We hope that providing up-to-date, clear information about our scientific expectations, such as clinical trial design and ways to measure effectiveness, will save companies time and resources and ultimately, bring effective new medicines to patients more efficiently.
These disease-oriented drug development guidances are an example of the strategies we’re implementing under the leadership of CDER’s director, Dr. Janet Woodcock, to modernize the agency’s new drug program.
The guidances also signal how modernization of the new drug regulatory program includes an enhanced focus on incorporation of patient input into our thinking. While the agency engages with patients on many fronts, this set of guidances showcases unique involvement from patient communities in collaborating with the FDA to make sure patient voices are heard. We will continue this type of partnership.
For example, the newly finalized Guidance for Industry “Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment” was preceded by a pioneering effort from Parent Project Muscular Dystrophy who, in 2014, submitted their own independent proposed draft guidance that provided important scientific and patient input from the DMD community. It helped inform the FDA’s development of both our own draft guidance and the final version issued today.
Another example is the new ALS-related guidance, “Draft Guidance for Industry – Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment.” Despite the availability of some approved therapies, there is an urgent need to identify additional effective treatments for patients with ALS. We’ve been honored to work with the ALS Association to advance these goals. The ALS Association put together a comprehensive proposed draft guidance of their own, funded by the famous “ice bucket challenge.” This proposed draft guidance, in turn, provided the FDA with scientific advice and insight into the disease that helped us advance our own draft guidance that provides our clear thinking on drug development in this area.
Another guidance of note that we’ve issued today is the revised “Draft Guidance for Industry: Early Alzheimer’s Disease: Developing Drugs for Treatment.” The FDA has been working closely with patients and the scientific community to gain the knowledge that will support intervention in very early AD in ways that have the potential to stop the disease before it causes clinical problems. This document describes innovative approaches to studying very early disease before the onset of dementia, including strategies for trials incorporating patients with Alzheimer’s who haven’t experienced any visible impairment (in the form of cognitive or functional deficits), but who may be identified through the use of sensitive cognitive screening, imaging tests, or biomarkers.
The “Guidance for Industry – Migraine: Developing Drugs for Acute Treatment” is the finalization of the draft guidance issued in 2014 that advances the field of migraine drug development by describing innovative approaches to clinical trial design for the assessment of effectiveness in treatment of acute migraine.
Also released today is the new “Draft Guidance for Industry – Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Effectiveness from Adult to Pediatric Patients 4 Years of Age and Older.” It describes a significant advance in the development of treatments for partial onset seizures in children. The guidance describes certain situations in which independent efficacy trials in pediatric patients are unnecessary and endorses a rigorous approach based on the extrapolation of effectiveness demonstrated in adult patients. The aim is to make the development of safe and effective treatments for pediatric patients suffering from these disorders more efficient.
We’ll be working on additional disease-specific guidance documents in the coming months; including those for treatments for opioid dependence and addiction. By providing modern guidance for the research and development communities and giving our drug review staff access to the best scientific tools, the FDA hopes to enable more efficient access to safe and effective, novel therapies for the patients.
The guidance documents we’ve issued today are an important step in facilitating efficient development of treatments for patients with serious neurological conditions. But they’re also just one part of our ongoing efforts to modernize the drug review process and foster beneficial new innovation. These changes, both outward facing and internal, will improve our ability to engage with sponsors, patients, and researchers, and adapt quickly to an environment where the science is changing at a breathtaking speed across many disease areas.
We’ll provide more details in the coming year on our work to make the drug development process more scientifically modern and efficient and continue to secure the FDA’s gold standard for product review, while we protect consumers. We look forward to receiving feedback on the guidances issued today and remain committed to providing helpful advice and engaging with drug developers to find treatments for unmet medical needs – harnessing innovation in the service of patients.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.