The FDA PDUFA Patient-Focused Drug Development Opportunity

Posted by: Carlo Rago on October 10, 2012

The FDA has provided a preliminary list of 39 nominated diseases - none are muscular dystrophy.  We need to work on this.

The fifth authorization of the Prescription Drug User Fee Act (PDUFA-V) offers an important opportunity to help accelerate therapies for Duchenne muscular dystrophy.  For each particular drug asset in each particular disease, the FDA (and, btw, all other stakeholders) must evaluate the risk to benefit ratio for therapeutic intervention.  While  scientific data serves as the basis for these critical decisions, patient perspectives on disease severity and need provides a deeper understanding of permissible risk and higher resolution to the prospective benefit.  In PDUFA-V, the FDA is seeking a more systematic approach to obtain patient perspectives to assist evaluation of risk to benefit ratios.

When I read the Federal Register (referenced below), I was under the impression that there were three upcoming opportunities to assist the FDA.  On October 10th, the FDA and patient advocacy groups were to discuss a communication framework for obtaining patient perspectives.  It was (still is) my understanding that the purpose of the October 25th meeting is to select 20 diseases for representation in the PDUFA-V program, but both the selection criteria and the list of selected diseases would be entirely negotiable.  It seemed that many of the advocates I met at the meeting were under the same impression.  I was, therefore, surprised by the suggestion that some diseases are so obviously in need that they are necessarily well-considered and may be excluded from the list of 20.  While there is an incredibly strong case for inclusion of Duchenne under the preliminary criteria suggested in the Federal Register, I'm fearing that there may be additional criteria that we need to consider.

Is the Duchenne patient perspective too well-represented for PDUFA-V consideration?

Our goal is to thoroughly inform the reviewers that control the many decision points any drug asset faces on the path to commercialization.  Are the reviewers aware of the spectrum of Dystrophin mutations and modifier genes that result in a wide range of outcomes for Duchenne and Becker?  Are the reviewers aware that women and the non-ambulatory population are under-served in clinical trials and that complex medical and ethical issues currently stand in the path of delivering promising breakthrough therapies to these groups?  What about steroid-induced obesity or depression in Duchenne?  There are complex issues for each prospective treatment at each stage of drug development for each of these subcategories, and patient perspectives will help to inform reviewers such that they can more accurately assess the risk to benefit ratio.

Some thoughts

1. Developing a systematic framework for obtaining patient perspectives is valuable to society and I think the FDA has done an a great job to initiate the conversation.  Very serious kudos.

2. If PDUFA-V intends to empower patient-directed drug development, then the FDA would be well-served to rely on the patient advocacy groups to determine the list of included diseases.   If the list of 20 is intended to bolster diseases with underrepresented patient perspectives, then it would be worthwhile to publish the findings and progress of those diseases that have well-represented patient perspectives - this will provide a more complete picture of the important progress at the FDA and may offer a preliminary framework for other diseases.

3.  If we are developing the framework for systematic success, the FDA would be well-served to start with a disease where there is dire unmet need.  A diverse but united and mobilized community may offer a wide range of both disease-specific and pervasive issues.  Duchenne Alliance?

Action Items

In preparation for the October 25th meeting, there are several things we can do to assist representation of Duchenne.

1. Help identify additional criteria for disease selection that may favor Duchenne.  I've posted the FDA's suggested criteria below.  Comment below if you have any ideas.
Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living;

Disease areas that reflect a range of severity;

Disease areas for which aspects of the disease are not formally captured in clinical trials;

Disease areas that have a severe impact on identifiable subpopulations (such as children or the elderly);

Disease areas that represent a broad range in terms of size of the affected population; or

Disease areas for which there are currently no therapies or very few therapies, or the available therapies do not directly affect how a patient feels, functions, or survives.

2. Help describe how we can apply the suggested criteria to nominate Duchenne.  If we identify additional criteria in the first action item, then also discuss how we can use those.  Please comment below if you have any suggestions.

The Duchenne community should generate a single, comprehensive document that clearly presents the patient perspective as a deliverable to the FDA by the 25th - this can be submitted to the docket and also in person.  It's my understanding that several foundations within the Duchenne Alliance will attend the meeting.

Do  you have a patient perspective that you would like the FDA to consider?  Is there another criteria that the FDA should consider in their selection of diseases  that will receive attention over the next 5 years?    The list of 39 candidate diseases can be found in reference 2 below.  Please leave a comment.


1 .  Prescription Drug User Fee Act V Patient-Focused Drug Development; Consultation Meetings; Request for Notification of Patient Stakeholder Intention To Participate

2.  Prescription Drug User Fee Act Patient-Focused Drug Development; Public Meeting and Request for Comments

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