Oct 26 2016

NORD Summit 2016 Highlights

By Kimberley Cummings, Ph.D., RAC (US), Vice President, Scientific & Regulatory Strategy and Operations Cato Research


The National Organization for Rare Disorders (NORD) held their annual Rare Diseases and Orphan Products Breakthrough Summit in Arlington, VA on October 17th and 18th.  If you have never been to this meeting before, it is the most unique and interesting mix of FDA representatives (and we are talking BIG names, too!), pharmaceutical/industry representatives, policy analysts, and patient advocacy groups along with several patients themselves.  That combination of individuals will certainly lead to some thought-provoking discussions, and if you follow any other industry blogs, then you have likely already seen some interesting highlights from this conference.

At last year’s Summit, the biggest news regarding Patient-Focused Drug Development and patient advocacy was that patients were, in fact, helping forge a path to approval as evidenced by the development and subsequent release of the FDA’s Guidance for Industry: Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment, a guidance largely drafted by the Duchenne advocacy community.  So, it was no surprise that this year, the discussion continued around potential drugs for Duchenne’s Muscular Dystrophy, but mostly on the recent somewhat controversial approval of Sarepta’s Exondys 51 (eteplirsen).  Not once or even twice, but at least three during the various sessions I attended, did an FDA or industry representative express their opinions on the approval of Exondys 51 only to result in an emotional rebuttal comment from a parent and/or advocate.  Clearly, charged conversations occurred during the approval process, and are still lingering today.

Rest assured, there were many other informative discussions that took place over the course of the 2-day summit.  Session topics included genetic innovation, advancing diagnoses, challenges of access and reimbursement, progress through policy, and understanding the pipeline and investment landscape for rare diseases and orphan products.  Presented here are some of the important take‑away messages from these various discussions:

  1. Rigorous data exploration has been and must remain the driver for drug development. Orphan drugs tend to be innovative (ie, first in class) and take advantage of FDA’s special programs, but development and approval must be based on strong science.  Furthermore, the development programs need to keep up with the ever-evolving science including innovations in telemedicine, genetic phenotyping, biosimilars, and advancements in CRISPR (clustered regularly interspaced palindromic repeat) technology, just to name a few.  In response to some of these advancing technologies, FDA has even reorganized to provide better oversight of gene therapy products; the office formerly known as the Office of Cellular, Tissue and Gene Therapies (OCTGT) has now become the Office of Tissues and Advanced Therapies (OTAT).  The formation of OTAT involves the transfer of the Office of Blood Research and Review’s Division of Hematology Clinical Review and Division of Hematology Research and Review, along with appropriate support staff, to OCTGT to constitute the new office.  The products now regulated by OTAT include all purified and recombinant versions of therapeutic proteins for hematology.


  1. Collaboration must continue between patient advocacy groups and the FDA, as well as among researchers through consortia. No one can hold all the knowledge.  This thinking is also supported by the Final Rule for the registering of studies and posting of results on Clinicaltrials.gov.  A panel discussion on collaboration across borders identified the increased interactions between FDA and EMA in regards to rare disease programs and suggested more international patient advocacy groups.  Furthermore, this panel confirmed the need for patient-driven registries, by disease, not by company, to collect natural history data and suggested a global depository system with standardized terms.  Progress in global outreach was substantiated by the establishment of the United Nations Committee for Rare Diseases.  This Committee will serve as an advocacy platform uniting around the issue of rare diseases a diversity of constituents which need to be more closely connected and collaborating with each other, including: the international non-governmental (NGO) community, major UN agencies, national governments, the academic and scientific world as well as the private sector.  The formal inauguration of the Committee is currently scheduled for November 11, 2016 at the United Nations headquarters in New York.


  1. In regards to patient advocacy collaboration, FDA continues to conduct the Patient Focused Drug Development (PFDD) meetings per the PDUFA V goals. A total of 24 PFDD meetings were planed from FY 2013-2017, and include the publication of a “Voice of the Patient” upon completion of the meeting.  To date, 20 meetings have been conducted, and only 4 remain.  These final 4 meetings will examine sarcopenia, autism, alopecia areata, and hereditary angioedema.  Upon completion of this PDUFA V goal, externally led PFDD meetings are expected to continue.  Meetings will be attended, but not organized by FDA; rather, a patient advocacy group or consortia would submit a letter of intent to the FDA 1 year in advance of the anticipated meeting date outlining the time, location, goal, objectives, outreach effort, and expected collaboration for the meeting.  Meeting organizers would also be expected to produce a “Voice of the Patient” report on their own website.


  1. FDA speakers confirmed for their audience that randomized clinical trials are the fastest way to determine clinical effectiveness. Especially in rare disease populations, every subject is critical, so valuable resources – either the subject themselves or a subject’s samples, should not be misused or wasted on poorly designed clinical trials.  To that end, the paradigm of early open-label studies shifted to randomizing subjects with rare diseases as early as possible and minimize time on placebo.  Emphasis was placed on the use of validated biomarkers and the need to report trial results early and accurately to obtain input from the FDA in regards to the clinical relevance of the biomarker and the plan for accelerated approval.  The audience was reminded that accelerated approval is NOT a rescue for a failed program, and that “any” effect of a drug on a biomarker does not equate to accelerated approval. Only a clearly defined and clinically relevant effect would suffice for accelerated approval.  Finally, post-hoc analyses should be used to design the next clinical trial, not as a basis for approval.


  1. As Natural History studies remain a critical component of rare disease and orphan product development, all stakeholders need to understand the natural history of a disease, and prospectively identify any natural history external controls. In regards to understanding the natural history of a disease, the Office of Orphan Product Development launched the Orphan Products Natural History Grants Program in 2016.  The goal of the grants program is to support studies that advance rare disease medical product development through characterization of the natural history of rare diseases/conditions, identification of genotypic and phenotypic subpopulations, and development and/or validation of clinical outcome measures, biomarkers and/or companion diagnostics.


  1. Officials at FDA working with rare diseases and orphan indications remain committed and VERY busy. Over the past 6 years, OOPD has seen a doubling of the number of orphan designations requests and will likely see a record number of designation requests this year.  To keep up with this demand, OOPD has had to expand the review time of a designation request from 90 days to 120 days.


Paul Melmeyer, NORD’s Associate Director of Public Policy, said it best when he said, “If you have a drug in the FDA process in the next 6 years, you should be involved with PDUVA VI.”  Given the timing of this meeting so close to a Presidential election, there was a particularly strong policy component to this year’s summit.  With the upcoming authorization of PDUFA VI, proposed bills already in review in Congress (including 21st Century Cures), and potential major healthcare changes with the approaching election, the next few months and years to come should bring about some small, and some not so small, changes in drug development, particularly for rare diseases and orphan indications.


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