FDA … 20 Diseases Being Chosen for PDUFA-V Meetings

Last Thursday, October 25th, I attended the FDA’s Patient-Focused Drug Development public meeting in Washington, DC. This meeting was required by the recently passed FDASIA/PDUFA-V legislation (see Abbreviation Decoder at end of post) and requires the FDA to hold 20 disease-specific meetings over the next 5 years to discuss topics such as:

“the impact of the disease on patients, the spectrum of severity for those who have the disease, the measures of benefit that matter most to patients, and the adequacy of the existing treatment options for patients.”

There were about 150 people in attendance and just over two dozen of us gave public testimony. The FDA is trying to get a better perspective on the needs, desires, and concerns of the patients by holding these 20 meetings.  Since we are directly impacted by the diseases we are best postured to tell them what’s most important to us.

Get involved … your letter to the FDA (see sample below) is needed by the end of the day November 1st! 

One common theme of the testimony was that the patients for each disease have a different risk tolerance for therapy.  Those with more slowly progressing and less severe diseases, or those diseases with existing approved therapies want new therapies studied in more detail while those of us with no therapy, faster progressions, or more severe disease symptoms are willing to take higher risks to accelerate the process to see if a proposed therapy will be effective.

For example, with late infantile MLD, being a clinical trial participant as part of the small patient sample in a typical two or three-year long trial, with the hope that there might be a positive outcome, is literally the difference between life or death if the outcome is positive.

With over 7,000 rare diseases and hundreds if not thousands of other more chronic diseases there is no way that 20 meetings is enough to address every specific situation.  Some of those giving testimony, myself included, recognized this and we expressed the idea of looking at the disease by the body system that is most affected to try to find common threads in therapy development, study, and approval.

Rare disease affects 1 in 10 of us across over 7,000 diseases, yet only two of those giving testimony, myself included, focused on the unique issues of rare diseases … no biomarkers, limited natural history, small patient populations to study, often very serious symptoms and fast progressions,  a disproportionate effect on children, most rare disease do not have any existing therapy, most rare diseases are ultra-rare with only a few hundred or thousand patients globally, etc. We feel that these sort of issues make studying and developing therapies/drugs for rare diseases especially difficult and unique.

With 35 million Americans affected by rare disease we need the special focus on the issues these 20 meetings will bring to the surface.

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For those of us with MLD, a related neuro-degenerative leukodystrophy or lysosomal disease, or any rare disease for that matter … this is our chance to take action to be well represented in the 20 meetings. The FDA only had a few hundred inputs as of last week.  Your letter will be read and is important. 

The FDA is requesting public input through the end of the day November 1st. I’ve given oral testimony directly to the FDA and am following up with written testimony. I hope you will take a moment to write a letter too – use the text below to get you started!

We have included three same letters to get you started depending on your own connection to rare disease, lysosomal disease, and/or MLD. We must have several rare diseases represented so we are quite comfortable if you take the more umbrella approach. Thank you to Jill Wood of Jonah’s Just Begun for basis of these letters).

Submitting your comments to the FDA is really easy:

    1. Choose one of the following three letters (Word template provided or copy & paste the text from the link)
      • MLD
        click here to download a Word .doc file
        click here to see the text (if you cannot use the Word .doc)
      • Lysosomal Disease with Neurological Manifestation
        click here to download a Word .doc file
        click here to see the text (if you cannot use the Word .doc)
      • Rare Diseases Letter
        click here to download a Word .doc file
        click here to see the text (if you cannot use the Word .doc)

      * Feel free to edit or add to the text as you see fit.
      * Add your name where indicated at the top of the letter
      * Personalize the second paragraph sharing your connection to rare disease, lysosomal disease and/or MLD. For example, mine will start … Two of my three daughters, one of whom is already deceased and the other is terminal with metachromatic leukodystrophy, an ultra-rare neuro-metabolic lysosomal storage disease.

    2. Please go to this online link to submit your comments: http://1.usa.gov/SaKQ4W
      * Fill in Section 1 on the left side of the form (name, e-mail etc)
      * Put MLD Foundation as organization, that field is required.
      * Leave the submitters representative name blank.
      * Choose the last option for category: Individual consumer (or choose international consumer if you are from outside the US).
      * Skip to the third section.  Upload the document you just created.
      * click Submit and you are done.
    3. If you have any problems submitting your comments please let me knowand I will try to help.


MLD Letter
click here to download a Word .doc file of this text or copy and past from below

[NAME]
[ADDRESS]
[CITY, STATE ZIP]

[don’t forget to edit the second paragraph!]

October 31, 2012

Re: Prescription Drug User Fee Act Patient-Focused Drug Development Meeting
Document ID FDA-2012-N-0967-0001

Submitted electronically to: http://1.usa.gov/SaKQ4W

Dear Committee Members,

Thank you for including the voice of the patient into the selection process for the 20 disease-specific meetings.

I write you as a parent to {YOUR FAMILY DESCRIPTION HERE}

I recommend adding Lysosomal Storage Disorders (LSD) with Neurological Manifestation to the list of nominated disease areas for the Patient-Focused Drug Development initiative and the criteria used for nomination, the initiative that is being conducted to meet the requirements enacted by PDUFA V.

Specifically, I’d like to recommend MLD – metachromatic leukodystrophy as a focus disease. I will summarize why MLD is an ideal candidate at the end of this letter.

We know every disease cannot be individually represented in just 20 meetings so we propose this group of lysosomal diseases that will provide unique research/therapy insight and will bring to bear the issues of developing therapies and drugs for ultra-rare and rare diseases.

I’m recommending this group of LSD’s because it cuts across multiple conditions represented in the preliminary list, groups together several diseases with similar physical manifestations, fits the criteria requested for additional disease area selection, and is poised for near-term treatment success.

Lysosomal diseases share unique drug development challenges with their rare disease siblings … such as having significantly smaller population sizes to study and recruit for trials from, a lack of well documented natural history, and inconsistencies in the extent of past research. In addition, the lysosomal diseases with neurological manifestations represent the generic challenges of ultra-rare populations that have very fast progressions and severe symptoms.

Neuro-LSD’s include over 45 diseases, 40 which affect children, and are universally fatal. Neuro-LSD’s share many similar challenges; a breakthrough in one of our diseases often opens similar lines of exploration in the remaining diseases.  They all share a challenge in getting drugs to reliably pass the blood-brain-barrier.

Currently, nearly all of the diseases nominated by the FDA have approved treatments. Meanwhile, there is not a single approved treatment that effectively addresses the 45 different Neuro-LSD’s. Our community finds the preliminary list egregious at best, and we hope you will consider the group of Neuro-LSD’s for the patient focused drug development initiative.

Lysosomal Storage Diseases fits all of the criteria requested for additional disease areas.

  1. LSDs are chronic, symptomatic, and have a devastating effect on the functions and activities of daily lives of the affected child and their families. Neurological effects include multiple types of seizures, ataxia, myoclonus, dystonia, tremors, chorea and spasticity. Many children affected by these disease regress to such a state that they require 100% care. They are unable walk, talk or eat via mouth – and after these painful losses, most die early deaths.
  2. LSDs with similar and identical gene defects exhibits a range of severity and age of onset. Some patients are affected at birth and range to include adult onset forms of these diseases.
  3. A previous lack of natural history studies, high-resolution clinical endpoints, and biomarkers resulted in aspects of the disease not previously captured in clinical trials.
    Many of the Neuro-LSD groups are developing global initiatives to address these needs – but today, the biomarkers and clinical endpoints generally do not exist due to the cost and difficulty of getting these endpoints for these ultra-rare diseases recognized by the FDA for clinical trial purposes.
  4. Neuro-LSD’s disproportionately affect the pediatric population. In most of these cases the disease is terminal. LSD’s may not represent a broad range in terms of size of the affected population, however, as a group, they do represent the most common inherited, pediatric, neurodegenerative disease group in the world.

Disease symptoms, as well as the underlying pathologies of these diseases, share many commonalities with more well-known neurodegenerative diseases affecting adult populations such as Parkinson’s, Huntington’s and Alzheimer’s diseases. While anti-epileptic medications have been shown to have a positive effect on seizure control, they simply hold the worst at bay for as long as possible. ALL of these temporary “treatments”, eventually fail in their goal of stopping seizures, as the lysosomal diseases continue their relentless progression.

Sadly, many of these children are keenly aware that their brains are rebelling against them, their bodies are failing, and that their lives are running in reverse, while their peers are moving forward. Recent developments in regenerative medicine, gene therapy, enzyme replacement, and drug discovery, are resulting in first-in-man studies for multiple forms of Lysosomal Storage Diseases. Investing in drug development that focuses on common mechanisms in the pathogenesis of multiple diseases could result in benefit for thousands of patients with rare and common illnesses. It is the right time to invest in translating discoveries into treatments for children who are in a race against time. Much progress has been made in understanding these diseases in the current age of genetic medicine. It would be a crime to let these discoveries languish due to a lack of interest or funds when we are so close to helping so many.

While any Lysosomal Disease with Neurological Manifestation, as described above would be a great focus disease, I’d like to highlight why MLD would be an excellent representative within that category.

MLD …

  • Is a neurological disease affecting both the central and peripheral nervous systems. Researchers do not understand why therapies targeted at the CNS do not seem to benefit the PNS.
  • Other body systems are affected by the loss of CNS/PNS capabilities.  MLD’s degradation includes cognitive as well as motor loss. Periods of seizures, contractures, high tone, loss of eyesight, difficulty breathing, and core temperature management are but some of the often painful challenges of MLD.
  • MLD is both a lysosomal disease and a leukodystrophy – we are one of only two diseases to be in both these also-rare disease umbrella categories. MLD is a white matter disease resulting from a defect in the lysosome of the cell.
  • Predominantly affects infants … but 20-25% of the cases are juvenile and another 20% or so are adult onset
  • We have over 200 mutations and the genotype-phenotype correlation is not well understood
  • We have no generally accepted biomarker or clinical end point
  • We have two clinical trials underway in Europe, but none here in the US. One of these trials was considered for application in the US and was rejected.
  • Our community is well-organized with almost 300 families tightly connected.  Our estimated population is approx. 200 patients in the US and a bit over 2,000 world-wide.
  • MLD is ultra-rare – our issues in understanding the disease are complicated by a wide-spread small population.  We have limited natural history and academic study underway. Ultra rare diseases exaggerate the problems that rare disease have with trial recruiting, study, and approval.
  • Stem cell transplant is the only therapy applied today.  Its mortality is too high, and its viability for post-symptomatic patients is negligible.  It has some CNS benefit for early symptomatic juveniles and adults – but is all cases PNS is not saved and the patients are trapped in immobile bodies.  In short, we really have no viable therapies today.
  • Time to death for the late infantiles is a few years.  These families, in particular, are very motivated to consider the risk/reward benefits of novel therapies – they cannot afford to wait to see if a therapy is safe and “will do no harm” because their children will be dead when that answer is known.
  • Families typically suffer a lengthy diagnostic odyssey and unfortunately that means the younger siblings benefit from the diagnosis of their older sister or brother who is to far advanced for clinical trial participation.
  • Two US-based firms/divisions are working on MLD therapies, and there are several academic institutions in the US and overseas with good knowledge of MLD

 

The MLD community is well-organized and sincerely wants to help the FDA serve us and those with other lysosomal and rare diseases better. Our community will participate at a focus meeting that will be collaboratively productive, not just table pounding and demanding.

Again, I implore you to add, Lysosomal Storage Disorders with neurological manifestations, all of which are ultra-rare diseases, and if possible, Metachromatic Leukodystrophy to the list of disease to be considered!  They are great proxies for all of the FDA criteria and what is learned through them will benefit many other related diseases.

 

Sincerely,

 

Lysosomal Disease with Neurological Manifestation
click here to download a Word .doc file of this text

[NAME]
[ADDRESS]
[CITY, STATE ZIP]

[don’t forget to edit the second paragraph!]

October 31, 2012

Re: Prescription Drug User Fee Act Patient-Focused Drug Development Meeting
Document ID FDA-2012-N-0967-0001)

Submitted electronically to: http://1.usa.gov/SaKQ4W

Dear Committee Members,

Thank you for including the voice of the patient into the selection process for the 20 disease-specific meetings.

I write you as a parent to {YOUR FAMILY DESCRIPTION HERE}

I recommend adding Lysosomal Storage Disorders (LSD) with Neurological Manifestation to the list of nominated disease areas for the Patient-Focused Drug Development initiative and the criteria used for nomination, the initiative that is being conducted to meet the requirements enacted by PDUFA V.

We know every disease cannot be individually represented in just 20 meetings so we propose this group of diseases that will provide unique research/therapy insight and will bring to bear the issues of developing therapies and drugs for ultra-rare and rare diseases.

I’m recommending this group of LSD’s because it cuts across multiple conditions represented in the preliminary list, groups together several diseases with similar physical manifestations, fits the criteria requested for additional disease area selection, and is poised for near-term treatment success.

Lysosomal diseases share unique drug development challenges with their rare disease siblings … such as having significantly smaller population sizes to study and recruit for trials from, a lack of well documented natural history, and inconsistencies in the extent of past research. In addition, the lysosomal diseases with neurological manifestations represent the generic challenges of ultra-rare populations that have very fast progressions and severe symptoms.

Neuro-LSD’s include over 45 diseases, 40 which affect children, and are universally fatal. Our group of Neuro-LSD’s share many similar challenges; a breakthrough in one of our diseases often opens similar lines of exploration in the remaining diseases.  They all share a challenge in getting drugs to reliably pass the blood-brain-barrier.

Currently, nearly all of the diseases nominated by the FDA have approved treatments. Meanwhile, there is not a single approved treatment that effectively addresses the 45 different Neuro-LSD’s. Our community finds the preliminary list egregious at best, and we hope you will consider the group of Neuro-LSD’s for the patient focused drug development initiative.

Lysosomal Storage Diseases fits all of the criteria requested for additional disease areas.

  1. LSDs are chronic, symptomatic, and have a devastating effect on the functions and activities of daily lives of the affected child and their families. Neurological effects include multiple types of seizures, ataxia, myoclonus, dystonia, tremors, chorea and spasticity. Many children affected by these disease regress to such a state that they require 100% care. They are unable walk, talk or eat via mouth – and after these painful losses, most die early deaths.
  2. LSDs with similar and identical gene defects exhibits a range of severity and age of onset. Some patients are affected at birth and range to include adult onset forms of these diseases.
  3. A previous lack of natural history studies, high-resolution clinical endpoints, and biomarkers resulted in aspects of the disease not previously captured in clinical trials.
    Many of the Neuro-LSD groups are developing global initiatives to address these needs – but today, the biomarkers and clinical endpoints generally do not exist due to the cost and difficulty of getting these endpoints for these ultra-rare diseases recognized by the FDA for clinical trial purposes.
  4. Neuro-LSD’s disproportionately affect the pediatric population. In most of these cases the disease is terminal.
    LSD’s may not represent a broad range in terms of size of the affected population, however, as a group, they do represent the most common inherited, pediatric, neurodegenerative disease group in the world.

Disease symptoms, as well as the underlying pathologies of these diseases, share many commonalities with more well-known neurodegenerative diseases affecting adult populations such as Parkinson’s, Huntington’s and Alzheimer’s diseases. While anti-epileptic medications have been shown to have a positive effect on seizure control, they simply hold the worst at bay for as long as possible. ALL of these temporary “treatments”, eventually fail in their goal of stopping seizures, as the lysosomal diseases continue their relentless progression.

Sadly, many of these children are keenly aware that their brains are rebelling against them, their bodies are failing, and that their lives are running in reverse, while their peers are moving forward. Recent developments in regenerative medicine, gene therapy, enzyme replacement, and drug discovery, are resulting in first-in-man studies for multiple forms of Lysosomal Storage Diseases. Investing in drug development that focuses on common mechanisms in the pathogenesis of multiple diseases, could result in benefit for thousands of patients with rare and common illnesses. It is the right time to invest in translating discoveries into treatments for children who are in a race against time. Much progress has been made in understanding these diseases in the current age of genetic medicine. It would be a crime to let these discoveries languish due to a lack of interest or funds when we are so close to helping so many.

 

Again, I implore you to add, Lysosomal Storage Disorders with neurological manifestations, all of which are ultra-rare diseases to this list!

Sincerely,

 

 

Rare Diseases Letter

click here to download a Word .doc file of this text

[NAME]
[ADDRESS]
[CITY, STATE ZIP]
[don’t forget to edit the second paragraph!]

November 1st, 2012

Re: Prescription Drug User Fee Act Patient-Focused Drug Development Meeting
Document ID FDA-2012-N-0967-0001)

Submitted electronically to: http://1.usa.gov/SaKQ4W

Dear Committee Members,

Thank you for including the voice of the patient into the selection process for the 20 disease-specific meetings under the Patient-Focused Drug Development initiative that is being conducted to meet the requirements enacted by PDUFA V.

I am directly impacted by rare disease [PUT YOUR FAMILY CONNECTION HERE]

We know every disease cannot be individually represented in just 20 meetings so we are advocating strongly for rare diseases be well represented as we believe all Americans will benefit form what is learned when we focus in on the challenges faced by those suffering from one of these 7,000 diseases.

1 in 10 Americans suffer from a rare disease, that’s over 30 million Americans. Rare diseases have significantly smaller population sizes to study and recruit for trials from, generally a less well documented natural history, and inconsistencies in the extent and documentation of past research.

Rare diseases affect all different body systems, ages, and come in a great range of severity and rate of progression.
* 80% of rare diseases are genetic in origin, and thus are present throughout a person’s life, even if symptoms do not immediately appear
* Approximately 50% of the people affected by rare diseases are children – 30% of children with rare disease will not live to see their 5th birthday
* Rare diseases are responsible for 35% of deaths in the first year of life
* The prevalence distribution of rare diseases is skewed – 80% of all rare disease patients are affected by approximately 350 rare diseases
* According to the Kakkis EveryLife Foundation, 95% of rare diseases have not one single FDA approved drug treatment
* During the first 25 years of the Orphan Drug Act, only 326 new drugs were approved by the FDA and brought to market for all rare disease patients combined
* According to the National Institutes of Health Office of Rare Disease Research, approximately 6% of the inquiries made to the Genetic and Rare Disease Information Center (GARD) are in reference to an undiagnosed disease
* Approximately 50% of rare diseases do not have a disease specific foundation supporting or researching their rare disease

Currently, nearly all of the diseases nominated by the FDA have approved treatments. As stated above, 95% of rare diseases do not have any treatment. Our community finds the preliminary list egregious at best, and we hope you will consider having rare diseases well represented in the 20 upcoming meetings.

I recommend that in addition to frequency of disease, FDA consider body systems affected as an alternative means to select the diseases for these meetings.

Rare disease fits all of the criteria requested for additional disease areas.

1. Rare diseases are chronic, symptomatic, and have a devastating effect on the functions and activities of daily lives of the affected child and their families. Many children affected by these disease regress to such a state that they require 100% care. They are unable walk, talk or eat via mouth – and after these painful losses, most die early deaths.

2. Rare diseases with similar and identical gene defects exhibits a range of severity and age of onset. Some patients are affected at birth and range to include adult onset forms of these diseases.

3. A previous lack of natural history studies, high-resolution clinical endpoints, and biomarkers resulted in aspects of the disease not previously captured in clinical trials.

4. Rare diseases disproportionately affect the pediatric population. In most of these cases the disease is terminal.

Again, I implore you to make sure that rare disease be a criteria for consideration for a number of the upcoming meetings!

Sincerely,

 

– Dean Suhr, President & Co-Founder, MLD Foundation, +1 503-656-4808

=====

Abbreviation Decoder:

    • FDA – Food & Drug Administration
    • FDASIA – Food and Drug Administration Safety and Innovation Act of 2012 … signed July 9, 2012, effective 2013 through 2017
    • PDUFA – Prescription Drug User Fee Act
    • Rare disease – defined differently in every country, in the US it’s any disease with a US patient population less that 200,000 people.
    • Ultra-rare – a non-specific term usually applied to rare diseases with a patient population of less than 6-10,000 individuals.
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4 thoughts on “FDA … 20 Diseases Being Chosen for PDUFA-V Meetings

  1. You have to click “Continue Reading” to see the rest of the post. I’ll go in and make that more obvious. Thanks for your support.

  2. Great that you’ve begun a blog! Thanks for your great work! I certainly want to send a letter to the FDA, but though it says see example below, there is no example or link to the FDA? Please get back to me soon so I can get others to write in also by the end of the day on November.

    Thank you SO much.

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