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Cyclodextrin

This page is dedicated to news and information about cyclodextrin, including the clinical trial currently being planned at the National Institutes of Health (NIH) for use in

Niemann-Pick Disease Type C (NPC). 


Glossary of Terms:

FDA                        United States Food and Drug Administration
HDAC                      Histone Deacetylase Inhibitors
ICV                          Intracerebroventricular
IND                          Investigational New Drug
i-IND                        Individual Investiational New Drug
IRB                          Institutional Review Board
NICHD                     National Institute of Child Health and Human Development
NIH                          National Institutes of Health
NPC                        Niemann-Pick Disease Type C Disease
TRND                      Therapeutics for Rare and Neglected Diseases


National Institutes of Health Key Cyclodextrin Trial Contacts

1st Contact
Lee Ann Keener

leeann.keener@nih.gov

(301) 594-2005
Clinical Research Nurse
2nd Contact
Nicole Farhat nicole.farhat@nih.gov
(301) 594-1765
Registered Nurse Clinician/Researcher (currently on a leave of absence)
  Dr. Forbes D. Porter     Prinicpal Investigator

National Institutes of Health  
Clinical Trial Updates for Niemann-Pick Type C Disease
June 27th, 2014
*Cyclodextrin and HDAC Inhibitor*

Update from Dr. Forbes D. Porter, MD, PhD
Senior Investigator, PDEGEN, NICHD
Program Head, PDEGEN, NICHD
Clinical Director, NICHD

The NNPDF central offices received the following update from Dr. Forbes D. Porter to share with the community in regards to recent developments in both the Cyclodextrin and new Histone Deacetylase Inhibitors (HDACi) clinical trials.

The TRND team continues to work to determine if cyclodextrin is a safe and effective therapy for children and young adults with Niemann-Pick Disease, type C1. This trial was initially started in January 2013 using Ommaya reservoirs; however, after three patients we had to stop the trial due to complications.  The trial was revised to administer the cyclodextrin by lumbar intrathecal infusion (spinal tap).  We were able to resume the trial in September of 2013 and to date we have enrolled twelve patients in whom we have studied cyclodextrin doses between 50 and 400 mg.  Some of the initial biomarker results look promising and we expect to obtain results from additional biomarker testing over the next few months.   From a safety perspective we are still concerned about ototoxicity (hearing loss) and we are working to try to better understand this issue.  Concurrent with this first trial we are working on a number of options that would support a phase II/III trial that would try to show that cyclodextrin has clinical benefit.    This second trial will need to be multisite and multinational.  

In addition to cyclodextrin, we are also exploring the potential use of histone deacetylase inhibitors (HDACi) to treat NPC1. The Maxfield and Sturley research groups showed that HDACi can reduce cholesterol storage in cells that have been cultured from NPC1 patients.     Over the past year we have been working to establish a proof of concept clinical trial of HDAC inhibition in NPC1.  A proposal to evaluate HDACi in NPC1 was awarded one of the first U01 grants (Drs. Maxfield, Ory and Porter) designed to promote extramural utilization of the NIH Clinical Center (http://www.nih.gov/news/health/mar2014/nichd-13.htm).  This collaboration has now been expanded this intramural/extramural collaboration to include investigators from Notre Dame (Drs. Helquist and Wiest), Broad Institute (Dr. Holson) and Mayo Clinic (Dr. Patterson).   This effort is being supported by Notre Dame College of Science and the Ara Parseghian Medical Research Foundation. The initial drug to be tested will be vorinostat.  Vorinostat is approved by the FDA for the treatment of cutaneous T-cell lymphoma.  Since this is a proof of concept trial and the safety of this drug in NPC subjects is not likely to differ significantly from patients with cutaneous T-cell lymphoma who have failed alternative chemotherapy, we were able to obtain a waiver of the requirement for an Investigational New Drug application for the testing of vorinostat in adult subjects with NPC1.  The NICHD Institutional Review Board (IRB) has approved a protocol to test the safety and efficacy of vorinostat in a cohort of 12 adult NPC1 subjects and we are currently working on IRB approval for a second site at the Mayo Clinic.  This will be a phase I proof of concept trial that will focus on safety of HDACi in NPC1 subjects and determine if HDAC inhibition has a desirable biochemical effect in white blood cells.  Although we still have a number of issues to resolve, it is our goal to initiate this protocol this fall. 

For more information about the HDACi Clinical Trial, visit the HDACi page.

[Jun 27th, 2014 ~ blg]


Meet Lee Ann Keener!

Keener 
Lee Ann Keener
Clinical Research Nurse, NIH

The National Niemann-Pick Disease Foundation is pleased to introduce you to Lee Ann Keener, newest member of the National Institutes of Health Therapeutics for Rare and Neglected Diseases program, Lee Ann Keener! 

While Nicole Farhat is away, Lee Ann will be stepping forward to be the primary NIH contact, so if you have any needs feel free to contact her.  Below is her biography she kindly provided for us.

"I graduated with my Bachelor of Science in Nursing from George Mason University knowing that I wanted to work with children. This led me to INOVA Fairfax Hospital for Children working on the Pediatric Hematology-Oncology unit. As I saw children being enrolled on research protocols for cancer therapies, I became interested in the details of how these protocols came to be and how the treatments were determined.

My curiosity led me to the National Institutes of Health where I started out as a Clinical Research Nurse working on the Inpatient Pediatric unit. When we started the Cyclodextrin trial, I became familiar with the NPC patients and their families, and was asked to join Dr. Porter’s team. I am very honored and excited to work with such an amazing group of people who are dedicated to scientific research for NPC!

I have certifications in pediatric hematology-oncology nursing, end-of-life nursing care, and holistic nursing.

I enjoy traveling, yoga, scuba diving, snowboarding, reading and playing with my 2 mini-dachshunds."

We welcome Lee Ann to the team and look forward to working with her!

[May 29th, 2014 ~ blg]

 

Scope

 

~Cyclodextrin Update~ 02/23/2014
NIH Update on NPC Cyclodextrin Trial
RE:  Cylodextrin Clinical Trial
~ From Dr. Forbes "Denny" Porter ~

Extra

Dear NNPDF Families and friends,

The NNPDF Central Office received the following message from Dr. Porter.

"We are resuming the trial per the protocol and will be exploring the safety and potential efficacy of higher doses of HPBCD.  Our safety committee and Institutional Review board supports continuing the protocol as initially planned.  

Denny

Forbes D. Porter, MD, PhD"



Scope

 

~Cyclodextrin Update~ 02/25/2014
NIH Update on NPC Cyclodextrin Trial

Extra

Dear NNPDF Families and Friends,

We received the following update from Dr. Denny Porter with reference to the NIH/TRND Cyclodextrin Clinical:

Dr. Porter advised: 
“We have hit a potential safety issue with the HPBCD trial.  The initial two kids who received the 300 mg dose demonstrated a grade 1 high frequency hearing loss on safety testing.  Grade 1 is the lowest level of severity.   Five other children have been exposed to the 300 mg dose.    We do not yet have safety testing on this group.  We will obtain this information over the next 3-4 weeks. We do not yet know if this is an idiosyncratic (the initial two kids are siblings) reaction or if this is going to be a general issue.   We have engaged the IRB and safety committee.  We will be engaging the FDA.   Our goals are to determine if we have a general safety issue and to figure out the best path forward.   Beyond the statement that a problem with hearing has been encountered and we are trying to figure out the safest and best way forward, there is not much that we can say.  There are multiple hypothetical paths forward at this time and the final plan is subject to information that we don’t have yet and input from other groups.  The uncertainty will remain for much of the next month.    We are not halting the trial.”      

Denny
Forbes D. Porter, MD, PhD
Senior Investigator, PDEGEN, NICHD
Program Head, PDEGEN, NICHD
Clinical Director, NICHD

As Dr. Porter noted, all involved will need to wait until the children in the trial return back to the National Institutes of Health in Bethesda, Maryland for further testing before the multiple agencies involved will be able to make any additional determinations on how to proceed.  Of course, of utmost concern is that any action will ensure that “first and foremost” ~  the health and safety of all involved is in the forefront.

Thank you to all for their continued expertise, support and involvement in these efforts.

Kind regards,
Nadine

[Feb 25th, 2014 ~ blg]


Lexington High School and Middle School
Releasing Balloons for Students in Clinical Trial

Ruthven
Kayla (13~ NPC) & Cody (18 ~ NPC) Ruthven

In Honor of the Ruthven Rockstars participation in the Cyclodextrin trial at the National Institutes of Health, the Lexington High and Middle Schools released 500 balloons on Monday, January 13th.

Cody & Kayla Ruthven are making their journey to Maryland for a two week stay to participate in the current drug trial for Cyclodextrin.  They are two of 9 children participating in the trial. After the first two weeks, they will return to the Institute once per month to receive the drug in hopes that it will save their lives.

The family has a blog specifically for their experiences while in the trial that can be found here: Cody and Kayla: On the Road to a Cure.

We wish Cody and Kayla the best of luck and look forward to sharing in this journey through their blog!

[Jan 15th, 2014 ~ blg]



WSJ

~Cyclodextrin Update~

“Trials ~ A Desperate Fight to Save Kids & Change Science”
By Amy Dockser Marcus ~ Staff writer for the Wall Street Journal
Dateline:  November 14, 2013

For six years, The Wall Street Journal followed a group of parents and scientists seeking a treatment for a rare and fatal genetic disease that strikes primarily children. Their collaboration accelerated development of a promising drug and, along the way, pushed the boundaries of medical research itself.

Follow this link to learn more about the story associated with Niemann-Pick Disease Type C here:

Trials: A Desperate Fight to Save Kids & Change Science

The members of the National Niemann-Pick Disease Foundation would like to offer a genuine note of thanks and heartfelt gratitude to the many individuals, families, community members, advocacy groups, as well as, esteemed members of the research and scientific community who all came together in a truly collaborative effort to see this process through to a clinical trial. 

A sincere note of thanks and appreciation goes out to this articles author, Amy Dockser Marcus, of The Wall Street Journal and her team of photographers, Evan Simon and Melissa Golden, for her unending devotion, dedication and perseverance, not only to the written word on the page which portrays the desperation and heartbreak that our Niemann-Pick Disease Families face at the diagnosis of their loved one, but to know how genuinely Ms. Marcus connected with the children and families she had the opportunity to work with.  She gathered them close, held them in her heart and helped them to build treasured memories.  For that, we are especially indebted.

Last, but certainly not least, are the sweet children and young adults diagnosed with Niemann-Pick Disease, whose families took the courageous step to move outside of their “safe-harbor” comfort zones and moved into the wider community and news media to share their families tragic diagnosis, knowledge, experience and personal sorrow. All of our Niemann-Pick Disease families will be forever grateful to those who braved sharing their heartbreak and personal circumstances for the wider NPD community.

We WILL one day, all stand together, hand-in-hand, and declare that we have Persevered in Our Quest for A Cure!

~ National Niemann-Pick Disease Foundation

[Nov 14th, 2013 ~ blg]


Scope

 

~Cyclodextrin Update~ 10/23/2013
NIH Update on NPC Cyclodextrin Trial

Extra

Dear Families and Friends,

The NNPDF Central Office received the below message from the NIH/TRND Team today which we are pleased to share with the NNPDF Community.

We are happy to share with the NPD community that the NIH/TRND Cyclodextrin in NPC1 trial has been restarted.  Despite the Federal Government shutdown from October 1-16, our team was able to meet our projected re-start date in late September, and to date have coordinated three successful admissions on this protocol.  We are grateful for the patience of the participating families, and for the dedication of the NIH Clinical Center staff, which allowed us to avoid any major interruptions in the admission schedule.

We have scheduled three additional patients to start before the end of 2013. The remaining open slots will continue to be scheduled on a rolling basis as we get closer to the start dates in early 2014.  We will be re-contacting families who had been screened previously to make sure they are still eligible before we schedule the remaining slots.  If any families with children ages 2-25 are interested in more information about the trial or would like a member of our team to screen their child to see if they are eligible, they can contact Nicole (Yanjanin) Farhat at (301) 594-1765 or email nicole.farhat@nih.gov .

To read the FULL letter, with eligibility criteria for the trial: Click Here.

[Oct 23rd, 2013~blg]



NNPDF August 2nd, 2013 Presentations on Cyclodextrin in NPC Disease

2013FCPanels
Aug 2nd, 2013 Panel Discussion Participants (from left); Dr. Andrew Mulberg (FDA);  Dr. Elizabeth McNeil (NeuroNEXT), Dr. Steven Silber (J&J), Dr. Caroline Hastings (CHORI), Dr. Patti Dickson (UCLA), Dr. Forbes “Denny” Porter (NIH), Dr. John McKew (NIH/TRND), Dr. Sara Goldkind (FDA), Dr. Dan Ory (NNPDF SAB), Dr. Marc Patterson (NNPDF SAB)

Helm

On August 2nd, 2013 in Baltimore MD, the National Niemann-Pick Disease Foundation (NNPDF) hosted a morning session on the use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as an experimental treatment of Niemann-Pick Type C (NPC) disease during its 21st Annual Family Support and Medical Conference .

To view the entire audio sessions, PowerPoint presentation and panel discussions ~ follow this link to the NNPDF Web site page titled:  NNPDF Aug 2nd, 2013 Presentation Cyclodextrin in NPC Disease.

In addition, more detailed information about the 21st Annual Family Support and medical conference can be located at:  http://www.nnpdf.org/familyservices_03.html

With follow-up photos and conference recaps at: http://www.nnpdf.org/FCRecaps.html

[Sept 11th, 2013 blg]


Scope

Cyclodextrin Update - 08/22/2013
NIH Update on NPC Cyclodextrin Clinical Trial

Dear NNPDF Friends and Families,

We are happy to share an update from Dr. Forbes “Denny” Porter, at the National Institutes of Health (NIH), that the Investigational New Drug (IND) hold by the Food and Drug Administration (FDA) has been lifted and the NIH team is working diligently to get the Internal Review Board (IRB) approval of the changes requested by the FDA. 

Dr. Porter has indicated that they expect to have the NIH Cyclodextrin clinical trial going again in September of 2013.  The NNPDF anticipates posting/sharing more of the specific clinical trial details with the full NPC community once the IRB approval is received. 

In the interim, Dr. Porter and his team wish to share with the community that this important and integral step with the FDA had been resolved!

Congratulations to all who have worked so hard and diligently on getting this process moving forward on behalf of our NPC patients and community members.

[August 22, 2013 blg]


Scope

Cyclodextrin Update - 05/16/2013
NIH TRND Cyclodextrin Clinical Team Update
NPC Community Wide Conference Call



             The NPC community-wide conference call was held on ~ Friday, May 3rd, 2013

Below we have provided links for a recording, transcript and follow up inquiries resulting from the May 3rd Cyclodextrin conference call with the NIH TRND Cyclodextrin Clinical team. We will continue to bring you more updates as they become available.

Wish to submit a question to one of our guest speakers?

    • Questions pertaining to the information presented during the call may be e-mailed directly to members of the NIH/TRND team and they will forward along to Drs. Ory and Porter for a response.  nichdnpc1@mail.nih.gov
The NNPDF would like to extend a kind note of thanks to members of the NIH/TRND Team for their continued expertice, care and concern for all in the NPC community and for assisting us in bringing you this latest NIH/TRND NPC Cyclodextrin Clinical Trial update.   In particular, we wish to recognize the ongoing and unending support from Dr. Forbes Porter, Dr. Dan Ory, Nicole Yanjanin and NPC Family Advocate, Jonathan Jacoby, their efforts know no bounds. 

                                                 We WILL Persevere in our Quest for a Cure!

Nadine Hill

NNPDF Executive Director

[May 16, 2013 blg]

*********************************************************************************************************************

 

Hello NPC Families and Friends,                                                                                 April 30th, 2013

The National Niemann-Pick Disease Foundation has been informed by Dr. Denny Porter, principal investigator of the NIH/TRND Cyclodextrin Clinical trial that the NIH team has decided to pause the Cyclodextrin clinical trial ~ currently being held at the NIH in Bethesda, Maryland, USA.  The NNPDF will host a NPC community-wide conference call, with Dr. Denny Porter and Dr. Dan Ory as the key speakers, to discuss this and other updates pertaining to the trial.

The NPC community-wide conference call will be held on ~ Friday, May 3rd, 2013 at:

*8:30 am PDT; 10:30 am CDT; 11:30 am EDT; 12:30 pm in Argentina and Brazil; 6:30 pm Israel

4:30 pm in UK; 5:30 pm in France, Germany, Holland, Italy, Poland, Spain, Switzerland. 

The following items will be addressed during the call:

  • Overview of the issues leading up to the decision to place the current trial into a pause status
  • The plan to continue the NIH Phase 1 clinical trial to evaluate the safety of Cyclodextrin in NPC1  
  • The NIH/TRND Cyclodextrin Clinical Trial team will continue to send additional follow-up correspondence to the NPC community world-wide regarding the protocol and status of same
  • Questions pertaining to the information presented during the call may be e-mailed directly to members of the NIH/TRND team and they will forward along to Drs. Ory and Porter for a response.  nichdnpc1@mail.nih.gov
  • This teleconference will be limited in time and recorded. A written transcript of the call will be posted and made available to the NPC community.
  • Questions during the call on Friday or resulting from the call can be emailed to: nichdnpc1@mail.nih.gov and will be responded to either on the call, if there is time, or after the call by direct e-mail. In addition, we will create a “Q & A” document resulting from these inquiries which will also be posted and made available to the NPC community.

Additional International "For-Toll" and "Toll-Free" numbers may be found by following this link.

Trouble accessing the call?

          •     For assistance dial or text:  920-650-3703
          •     E-mail:  nnpdf@nnpdf.org
          •     The details and follow-up from this call will be made availalbe to   our entire NPC global community via a recording and transcribed notes

How can you be of help?

          • Please note:  If you are able to connect via Skype and/or have Free long-distance ~ we encourage you to utilize these sources to assist us in keeping the overall cost of this call down.

If you have any questions pertaining to this notification ~ please feel free to e-mail the NNPDF Central Offices at:  nnpdf@nnpdf.org.

Thank you for your kind consideration to this matter.

Nadine M. Hill
NNPDF Executive Director
National Niemann-Pick Disease Foundation
www.nnpdf.org
E-mail:  nhill@nnpdf.org
Phone:  920-563-0930

[Apr 30th, 2013 blg]


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The Anatomy of a Clinical Trial

~ April 21, 2013 ~

A recent article by the Greenwich Times detailed a sit down Q & A session with Dr. Steven Walkley to spread awareness and talk about the current Cyclodextrin Trial.

Q: What does this NIH trial involve?

A: New therapies must be tested rigorously in a controlled setting to make sure that they are both safe in humans and truly effective against the disease. While animal studies are suggestive, and help to provide the needed information to get to the trial stage, they are not definitive. The scientists have presented enough compelling data on this new treatment, cyclodextrin, to have received approval from the FDA to begin with a Phase 1 clinical trial in humans. This is the necessary research to get to the next stage and hopefully find an effective treatment for NPC. The trial will have three stages and may take several years to complete before the drug can be approved for widespread use by the FDA. Andrew Marella and the other few children who are participating in the current NIH trial will help determine the safety of the drug in humans. The next phases will show the efficacy of the drug.

To read the full article, Click Here.

 

[Apr 22nd, 2013 blg] 


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Old Drug Offers New Hope Against Rare, Deadly Childhood Disease

~ Apr 4th, 2013 ~

Dear NPD Community,

The Gordon conference on lysosomal diseases begins on Sunday, April 14th- 19th in Lucca, Italy.

This second Gordon Research Conference on Lysosomal Disease will have cutting-edge research sessions on topics ranging from the basic science of lysosomal biology to disease cascades and new therapies for specific diseases. Sessions will focus on molecular and cellular pathogenesis, the relationships of lysosomal diseases to other disorders, biomarker development, innovative approaches to therapy, and clinical trials and design.

Six members of the NNPDF scientific advisory board will be presenting research or in attendance. The amount of collaboration going on there is amazing!

For more information, Click Here

[Apr 12th, 2013 blg]

 

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Cyclodextrin Trial Article

~ Mar 4th, 2013 ~


Dear NPD Community,

On February 28th, in recognition of 2013 World Rare Disease day, the Maryland Gazette did an article on Dillon Papier's participation in the National Institue of Health's Cyclodextrin Trial.

[Mar 4, 2013 blg]


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NIH Announcement - Cyclodextrin Trial Update

~ January 31st, 2013 ~


Dear NPD Community,

The NNPDF central offices received the following update on the Cyclodextrin trial from the NIH Research Team.

"The NIH cyclodextrin trial has started and the first patient will receive the drug on Monday 2/4.  We are very excited to get started and to get data that will direct future studies of cyclodextrin in NPC.  We have been in contact with many families and would like to provide an update about the trial screening process.

The patients in this trial are grouped into "cohorts" of three patients each.  Because we did not know exactly when we would be able to start the trial, the first three patients were selected because they live relatively close to the NIH or were able to come to the NIH with very little notice (less than 2 weeks in one case).  Only the first 3 patients have been scheduled.  We have not yet filled the remaining slots for the trial.

The FDA asked us to start at a lower dose than we initially proposed.   The initial data from these first three patients will determine what exactly we will do next.  We decided that we will need to re-screen patients when we are ready to schedule the next cohort (patients 4, 5 and 6), in order to make sure they are still eligible.  This will also need to happen again with the last 3 patients.  We have a screening log of all individuals who we have screened and will be in touch with families when we are prepared to schedule the remaining slots in the trial.

We would like to thank you for your continued patience and we apologize for any delays in returning phone calls or emails.  We are doing our best to get this trial going as quickly and safely as possible so we can answer questions about cyclodextrin in NPC.  Please do not hesitate to contact us with additional questions.

The NIH NPC Research Team"

[Jan 31, 2013 blg]

 


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NIH Announcement - Clinical Trial and Protocol

~ January 28th, 2013 ~


Dear Families and Friends,

The foundation board members and families of the National Niemann-Pick Disease Foundation are pleased to share with our supporters and constituents the following press release from the National Institutes of Health (NIH) in Bethesda, Maryland.  The approval to move forward with this clinical trial from the United States Food and Drug Administration (FDA) is the culmination of two long years of hard work to advance a promising therapy for Niemann-Pick Disease Type C from the laboratory bench of a researcher to the bedside of a patient. 

~ NIH Press Release Announcing NPC Clinical Trial (dated: 01/23/2012)
~ NIH/TRND NPC Team Announcement of FDA approval (dated: 01/11/2013)
~ NIH/TRND NPC Cyclodextrin Clinical Trial Protocol (dated: 11/28/2013)

While we are eager to see this trial move forward as the first possible therapy for children and young adults diagnosed with the neurological terminal disease known as Niemann-Pick Disease Type C, we move forward cautiously, as this trial is in essence an experiment.  The families of the children and young adults involved are taking a courageous step forward on behalf of all those who suffer from this debilitating and fatal disorder and in memory of all those who have lost their brave battles with Niemann-Pick Disease (NPD) in years past.  The NNPDF realizes that this trial would not be moving forward towards a possible treatment were it not for the ongoing spirited support and  financial backing from the families, friends and communities around the country where children and young adults with NPC reside.  We are indeed deeply indebted.

We WILL Persist in our Quest for a Cure

Kind regards, Nadine Hill

Nadine M. Hill

Executive Director

National Niemann-Pick Disease Foundation, Inc.

[Jan 28, 2013 nmh]


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UPDATE: Cyclodextrin Trial Press Release!

~ January 23rd, 2013 ~


Dear Families and Friends,

The NNPDF central office received the following press release from the National Institute of Health (NIH) NPC Clinic from Dr. Forbes "Denny" Porter with an update on the Cyclodextrin Trial.

Click Here to see the press release.

[Jan 23, 2013 blg]

 


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UPDATE: FDA Approves NIH TRND Team for NPC Cyclodextrin Clinical Trial!

~ January 11th, 2013 ~


Dear Families and Friends,

The NNPDF central office received the following update from the National Institute of Health (NIH) NPC Clinic from Dr. Forbes "Denny" Porter.

"We were informed today that the FDA has removed the clinical hold on the hydroxypropyl-β-cyclodextrin trial.  We are planning to enroll the first patient in two weeks.   This trial is a major step in trying to determine if this is a safe and biochemically effective drug for NPC.  Our goal is to use data from this trial to optimize the design of a larger second trial focused on clinical efficacy.  Thank you for your help and support!

The TRND Team"

[Jan 11th, 2013 blg]


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Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin

~ January 4th, 2013 ~


Dear Families and Friends,

The NIH 2-hydroxypropyl-β-cyclodextrin trial has been put on hold by the FDA.  The FDA had specific issues regarding the trial, the majority of which we were able to resolve during a teleconference on December 10, 2012.  However, there were questions concerning the compatibility of the drug and the Ommaya reservoir.  Both Johnson and Johnson and Integra (the manufacturer of the Ommaya reservoir) provided significant assistance in helping to answer these questions. 

The FDA was provided with our complete written response to their questions on December 13th and we provided an updated protocol on December 31st.  We are currently waiting for the review of our response from the device division, and we believe that we have adequately addressed their concerns.  The FDA has 30 days (plus Federal holidays) from December 13th to provide a formal response.  In order to allow for this, we have moved back our targeted start date by two weeks to the end of January 2013.  This will allow us time to accommodate a positive response from the FDA and to reconcile any changes with what the NICHD IRB has approved.     

We fully understand the disappointment that this message entails; however, we are committed to resolve any further questions that the FDA may raise.  Despite this delay, we are hopeful that we are very close to the start of the trial.  We will plan to update the NPC1 community as more information becomes available.  

The TRND Team

[Jan 4th, 2013 blg]


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Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin

~ December 14th, 2012 ~


Dear Families and Friends,


The NNPDF has received the following update this afternoon from Dr. Porter at the National Institutes of Health with reference to a current status on the TRND NIH NPC Cyclodextrin Clinical Trial “IND” application with the FDA:

"We would like to update the NPC community with regards to the HPBCD protocol. During our teleconference on Monday the FDA requested additional information related to the protocol. We worked with the FDA on Monday to resolve most of the concerns, and we were able to provide data related to the additional questions this week. In conversation with the FDA today, our responses are under review.

We will provide the NPC community with another update as soon as we can. Thank you for your support."

Denny, Forbes D. Porter, MD, PhD

Senior Investigator, PDGEN, NICHD

Acting Program Director, PDEGEN, NICHD

Clinical Director, NICHD

Please be advised that the NNPDF will continue to forward and provide information about the clinical trial as it becomes available from the National Institutes of Health. More information about the TRND NIH NPC Cyclodextrin Trial is available at this web site link:  http://www.nnpdf.org/Cyclodextrin.html


Kind regards, Nadine Hil
l

 

Nadine M. Hill

Executive Director

National Niemann-Pick Disease Foundation, Inc.

[Dec 14th, 2012 nmh]


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Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin

~ December 11th, 2012 ~

Hello NNPDF Families and Friends,

The National Institutes of Health (NIH), in collaboration with the Therapeutics for Rare and Neglected Diseases Program (TRND), is developing a clinical trial utilizing cyclodextrin for Niemann-Pick Type C (NPC) patients.

The TRND NIH NPC Team working on the FDA “IND” (Food and Drug Administration “Individual New Drug”) clinical trial application met yesterday (Monday, December 10th, 2012) via a telephone conference call with representatives from the Food and Drug Administration overseeing the teams clinical trial application.  During the call, the FDA addressed some issues that the NPC Team must address as it pertains to the IND application.

Currently, all time and talent of the associated TRND NIH NPC team members is being directed to this task so that they can respond to the FDA representatives as soon as possible.

The TRND NIH NPC team has advised that they expect to receive additional feedback on the requested clinical trial protocol from the Food and Drug Administration by this Friday, December 14th, 2012 (the end of the 30 day review period.) 

The members of the TRND NIH NPC team have advised that they will let us know about the FDA’s response/feedback as soon as it becomes available.  The NNPDF will continue to monitor these matters and advise.

Kind regards,

Nadine Hill; NNPDF Executive Director

[Dec 11th, 2012 blg]


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Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin

~ December 7th, 2012 ~

An informational conference call/webinar was held on November 6th in regards to an update on the NIH TRND Cyclodextrin trial.

The National Institutes of Health (NIH), in collaboration with the Therapeutics for Rare and Neglected Diseases Program (TRND),  is developing a clinical trial utilizing cyclodextrin for Niemann-Pick Type C patients. The clinical trial is the final stages of collecting and receiving approval from the Food and Drug Administration in the United States to move a head on a Phase I trial.

Below are links to informational material discussed during the call:.

Unfortunately, the program recording the session malfunctioned and we were unable to retrieve it, but a written summary will be forthcoming.

[Dec 7th, 2012 blg]  


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Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin

~ November 28th, 2012 ~

                  Cyclodextrin (HP-β-CD) for NPC1 Disease

                            ~ Clinical Trial Strategy ~

UPDATE ~ November 28th, 2012 ~ UPDATE

Therapeutics for Rare and Neglected Diseases (TRND)

National Institutes of Health ~ Bethesda, MD

Dear National Niemann-Pick Disease Foundation Family Members,

The latest release pertaining to the upcoming NIH NPC clinical trial has been made available to the NNPDF. To view the NIH NPC Cyclodextrin Clinical Trial Flyer ~ dated: 11/28/12 ~ click here.

This study titled: 2-hydroxypropyl-B-cyclodextrin (HP-B-CD) in Niemann-Pick Disease, type C1, is in the process of being reviewed by the FDA and the team of researchers and physicians associated with the Therapeutics for Rare and Neglected Disease ~ Niemann-Pick Type C Disease Team (TRND NPC Team) at the NIH are hopeful that they will be able to begin enrolling patients in January of 2013.

The National Niemann-Pick Disease Foundation is pleased that we are able to forward this information along to our family membership. The NIH attached flyer specifies that interested parties should note your interest in possible trial participation by e-mailing a representative at the NIH: nichdnpc1@mail.nih.gov

Please note: If you do NOT have access to the internet or an e-mail account please contact the NNPDF Central Offices at the 920-563-0930 and we will assist you in reaching the appropriate contact individual(s) at the NIH for more information.

This is indeed, a very exciting time for all of our NNPDF family community and, more importantly, all of our precious loved ones diagnosed with Niemann-Pick Disease Type C

.

We WILL Persevere in our Quest for a Cure!

Kind Regards, Nadine M. Hill

Executive Director; National Niemann-Pick Disease Foundation

For a historical timeline on the Cyclodextrin (HP-β-CD) for NPC1 Disease Clinical Strategy ~ outlined by the NNPDF ~ please follow the link above.

[Nov 28, 2012 nmh]


Group meeting

Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin

~ November 2012 ~

Cyclodextrin (HP-β-CD) for NPC1 Disease

~ Clinical Strategy ~

Nuria Carrillo, MD

Therapeutics for Rare and Neglected Diseases (TRND)

National Institutes of Health ~ Bethesda, MD

Please follow this link to view of PowerPoint presentation titled:

Cyclodextrin (HP-β-CD) for NPC1 Disease ~ Clinical Strategy ~

Created and presented by:

Nuria Carrillo, MD; Staff Clinician

Therapeutics for Rare and Neglected Diseases (TRND)

Division of Preclinical Innovation

National Center for Advancing Translational Sciences

National Institutes of Health ~ Bethesda, MD

  

For questions email us at nyanjanin@mail.nih.gov

[Nov 21, 2012 nmh] 


Group meeting

Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin

~ November 2012 ~

Planned Phase I Study of Cyclodextrin (HP-β-CD) for NPC1 Disease

Since our last communication in September 21, 2012, the National Institutes of Health Therapeutics for Rare and Neglected ~ Niemann-Pick Disease Type C team has continued to move forward in the preparation of the Phase I Study of Cyclodextrin (HP-b-CD) for NPC1 Disease.

The TRND NPC Team is pleased to announce that the Investigational New Drug (IND) application for intraventricular hydroxypropyl-β-cyclodextrin (HPBCD) was filed with the FDA today, November 14th.  This was a major effort by multiple research laboratories, several NIH institutes,  Johnson and Johnson and a team of pharmaceutical and regulatory consultants.  This effort would not have been possible without the assistance of the many patient support organizations.

Our ultimate goal is to develop a safe, effective and accessible  therapy for all individuals with NPC1.  The IND filing is a major step in this process, but just one of the initial steps.  We are hopeful that the very promising preclinical findings in mice and cats will translate to an effective therapy in individuals with NPC1.  The goal of this first trial is to rapidly determine a safe and biochemically effective dose of HPBCD.  These data are critical to the proper design and execution of a multicenter efficacy trial that will allow this drug, if determined to be safe and effective, to be approved by regulatory agencies, and ultimately to be made available to all NPC1 patients.

We appreciate the ongoing support from the NPC community and will continue to update the community on this trial.

For questions email us at nyanjanin@mail.nih.gov

Respectfully submitted by:

    TRND  NPC  Team

Therapeutics for Rare and Neglected Disease ~ Niemann-Pick Type C Disease Team

FDA                        United States Food and Drug Administration

HDAC                      Histone Deacetylase Inhibitors
ICV                          Intracerebroventricular

IND                          Investigational New Drug

IRB                          Institutional Review Board

NICHD                     National Institute of Child Health and Human Development

NIH                          National Institutes of Health

NPC                        Niemann-Pick Disease Type C Disease

TRND                      Therapeutics for Rare and Neglected Diseases

                 NPC Team TRND FDA Nov 1 2011

Members of the TRND ~ NPC Team.  Photo taken on Nov 1, 2011, at an update meeting with the FDA.

Front row (left to right): Ilona Scott (J&J), Pat Frenchick (RRD), Sandie Morseth (RRD), Kimberly Lilly (RRD), Mark Kao (J&J), Nicole Yanjanin (NIH/NICHD), Liz Ottinger (NIH/TRND), Nuria Carrillo-Carrasco (NIH/TRND), Xin Xu (NIH/TRND)
Second row (left to right): Steve Walkley (Albert Einstein College of Medicine), Charles Vite (UPenn), Chuck Finn (RRD), Joy Vander Wal (RRD), Steven Silber (J&J), John McKew (NIH/TRND), Denny Porter (NIH/NICHD), Dan Ory (Washington University School of Medicine), Chris Austin (NIH/TRND), John Heiss (NIH/NINDS), Wei Zheng (NIH/TRND)
Not pictured: Juan Marugan (NIH/TRND), Bill Pavan (NIH/NHGRI), and Pramod Terse (NIH/TRND)

[Nov 14, 2012 nmh] 


Group meeting

Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin

~ September 2012 ~

Planned Phase I Study of Cyclodextrin (HP-β-CD) for NPC1 Disease

Since our last communication in December 2011, the National Institutes of Health Therapeutics for Rare and Neglected ~ Niemann-Pick Disease Type C team has continued to move forward in the preparation of the Phase I Study of Cyclodextrin (HP-b-CD) for NPC1 Disease.

The goal of the NIH/TRND NPC team is to collaboratively develop a safe, effective and FDA-approved therapy for patients with NPC1.  The protocol has undergone ethics review by the National Institute of Child Health and Human Development (NICHD) Institutional Review Board (IRB) and they requested only minor changes. 

Currently we are expecting to submit an Investigational New Drug (IND) application to the Food and Drug Administration (FDA) before the end of 2012.  To date, our major issue has been completing the juvenile dog study that the FDA has requested.  If no problems are encountered with the IND, we are anticipating that the clinical trial will start in January.

The goal of this Phase 1 trial is to establish safe and biochemically effective dosing regimen for HP-b-CD treatment of human NPC1 subjects. To attain this we are using a systematic, controlled, and scientifically rigorous approach. HP-b-CD will be given by intracerebroventricular (ICV) administration via an Ommaya reservoir. This dose escalation study will include 9 patients divided in 3 dosing cohorts. The study is designed to determine the best benefit-risk profile, determine whether dose or time of treatment is most important in NPC and to avoid giving suboptimal doses. Information of the eligibility criteria will be available once the protocol is approved.

If a safe and biochemically effective dose is determined in this Phase I study, we plan to move forward with a Phase II, multi-center trial to evaluate for efficacy.  Planning for this trial is already in progress. 

For questions email us at nyanjanin@mail.nih.gov

Respectfully submitted by:

    TRND  NPC  Team

Therapeutics for Rare and Neglected Disease ~ Niemann-Pick Type C Disease Team

FDA                        United States Food and Drug Administration

ICV                          Intracerebroventricular

IND                          Investigational New Drug

IRB                          Institutional Review Board

NICHD                    National Institute of Child Health and Human Development

NIH                          National Institutes of Health

NPC                        Niemann-Pick Disease Type C Disease

TRND                     Therapeutics for Rare and Neglected Diseases

                 NPC Team TRND FDA Nov 1 2011

Members of the TRND ~ NPC Team.  Photo taken on Nov 1, 2011, at an update meeting with the FDA.

Front row (left to right): Ilona Scott (J&J), Pat Frenchick (RRD), Sandie Morseth (RRD), Kimberly Lilly (RRD), Mark Kao (J&J), Nicole Yanjanin (NIH/NICHD), Liz Ottinger (NIH/TRND), Nuria Carrillo-Carrasco (NIH/TRND), Xin Xu (NIH/TRND)

Second row (left to right): Steve Walkley (Albert Einstein College of Medicine), Charles Vite (UPenn), Chuck Finn (RRD), Joy Vander Wal (RRD), Steven Silber (J&J), John McKew (NIH/TRND), Denny Porter (NIH/NICHD), Dan Ory (Washington University School of Medicine), Chris Austin (NIH/TRND), John Heiss (NIH/NINDS), Wei Zheng (NIH/TRND)

Not pictured: Juan Marugan (NIH/TRND), Bill Pavan (NIH/NHGRI), and Pramod Terse (NIH/TRND)

[Sep 21, 2012 nmh]


Development of Therapeutic Interventions for Niemann-Pick Disease, Type C1

Videocast of Presentation by Dr. Forbes D. Porter, NIH

Denny Porter


Dr. Forbes "Denny" Porter of the National Insitute of Child Health and Human Development, National Institutes of Health, presented Clinical Center Grand Rounds at the National Institutes of Health on May 16, 2012.  Dr. Porter's presentation was titled Development of Therapeutic Interventions for Niemann-Pick Disease, Type C1.

The NIH produced a videocast of Dr. Porter's presentation, and you can watch the video or download it from this link (Dr. Porter's presentation is approximately the first half of the 45-minute video):

http://videocast.nih.gov/Summary.asp?File=17266

[May 25, 2012 mem]

 



Group meeting

Niemann-Pick Disease Type C to be Spotlighted at NIH Rare Disease Day Event

Denny Porter, M.D., Ph.D., of the National Institute of Child Health and Human Development (NICHD), NIH, together with Mark Kao, Ph.D., of Johnson & Johnson, and John McKew, Ph.D., of Therapeutics for Rare and Neglected Diseases (TRND), NCATS, NIH, will speak about the upcoming cyclodextrin trial for NPC at a Rare Disease Day event being hosted at the NIH. 

The day-long event will recognize rare disease research activities supported by several government agencies and advocacy organizations.

Attendance is free and open to the public and the media, and pre-registration is encouraged. In association with the Global Genes Project (a grassroots effort to use jeans to raise awareness for rare genetic disorders), organizers urge all attendees to wear their favorite pair of jeans.

For more information about the Rare Disease Day event at NIH, read the NIH press release.   

See the full agenda and register for the NIH event via links at http://rarediseases.info.nih.gov/RareDiseaseDay.aspx.

For more information about the TRND project and the upcoming cyclodextrin trial, visit our special page.


Group meeting

Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin


The NIH/TRND NPC team met again with representatives of the FDA on Tuesday, December 13, to discuss plans for the upcoming clinical trial of cyclodextrin, and we are pleased to be able to share the update below.

NNPDF members can be assured the foundation will continue to keep families up-to-date on information about plans for this and all clinical trials as details become available.   Updates will be posted here to the NewsLine page, as well as to the Facebook page and the listserv groups.

For more information about TRND (Therapies for Rare and Neglected Diseases program) and the six pilot projects selected (including NPC), see this press release from NIH.

Update from the December 13 meeting:

Dear families and friends of the NPC community,

The collaborative group planning a cyclodextrin clinical trial at the National Institutes of Health (NIH) for the treatment of Niemann-Pick type C (NPC) disease met with the Food and Drug Administration (FDA) on Tuesday, December 13, 2011 as a follow up to the recently held November pre-IND meeting.  On November 1, we met with the FDA Review Division staff to discuss the proposed development plan for cyclodextrin and needs for the IND application package.

Representatives from the Therapeutics for Rare and Neglected Diseases (TRND) group at the NIH, as well as several NPC researchers, Johnson & Johnson, and consultants from RRD International, LLC, participated in this meeting.

While the November meeting focused on the drug safety and toxicology data, the purpose of the December meeting was to discuss the proposed clinical trial design.  Overall, the feedback from FDA was very positive and their comments and guidance will assist us in the generation of an IND application that is agreeable to FDA, thus allowing us to move forward with the initial clinical trial as soon as possible.

Preclinical toxicology and safety studies in animals are ongoing, and additional studies will be initiated shortly.  These required nonclinical studies will guide the selection of drug doses for the initial trial and will provide essential safety information.   In the upcoming months, we will be evaluating these study results and will incorporate them into the  IND application and initial clinical protocol, which will then be submitted to FDA and the NIH Institutional Review Board (IRB).  Once we have agreement from FDA and approval from the NIH IRB, we can share the specific details of the initial clinical trial, such as patient inclusion/exclusion criteria.

We are very excited about the progress we have made thus far and are encouraged by our recent meetings with FDA.  We understand that the community is eager to start this initial trial as soon as possible and we do not have time to waste.  Following the meeting, we believe that FDA shares our sense of urgency and we are grateful that they are willing to work closely with us to get this important initial trial started.  As always, your support of NPC research is the final piece that will help us impact this disease.  Thank you for your enthusiasm, your patience, and especially for trusting that we are making every effort to help individuals and families affected by NPC.

The TRND Team

[Dec 16, 2011 mem]


Update -- Upcoming Cyclodextrin Trial
National Institutes of Health (NIH)

A message from Dr. Denny Porter at NIH:

[Here is] an update on the TRND FDA meeting held this past Tuesday.  We still have a lot of hard work to do, but the meeting was positive.  I am including a picture of the TRND Team that participated in this meeting.  It is an impressive collection of expertise and this group has greatly facilitated moving the effort to develop a safe and effective therapy for NPC forward.  We know the photo is missing one critical facet of the team - the families.

Thank you for your support.

Denny, Nicole and Nuria

Forbes D. Porter, MD, PhD; Senior Investigator, PDGEN, NICHD
Acting Program Director, PDGEN, NICHD; Clinical Director, NICHD

 Follow this link to read the November 4th, 2011, announcement:     Cyclodextrin Trial Update 11-4-11

NPC Team TRND FDA Nov 1 2011

                           Members of the NPC Team.  Photo taken on Nov 1, 2011, at an update meeting with the FDA.

Front row (left to right): Ilona Scott (J&J), Pat Frenchick (RRD), Sandie Morseth (RRD), Kimberly Lilly (RRD), Mark Kao (J&J), Nicole Yanjanin (NIH/NICHD), Liz Ottinger (NIH/TRND), Nuria Carrillo-Carrasco (NIH/TRND), Xin Xu (NIH/TRND)

Second row (left to right): Steve Walkley (Albert Einstein College of Medicine), Charles Vite (UPenn), Chuck Finn (RRD), Joy Vander Wal (RRD), Steven Silber (J&J), John McKew (NIH/TRND), Denny Porter (NIH/NICHD), Dan Ory (Washington University School of Medicine), Chris Austin (NIH/TRND), John Heiss (NIH/NINDS), Wei Zheng (NIH/TRND)

Not pictured: Juan Marugan (NIH/TRND), Bill Pavan (NIH/NHGRI), and Pramod Terse (NIH/TRND)

[Nov.4, 2011 nmh]



Doctor with child and its mother

Wall Street Journal Health Blog Article: 
Cyclodextrin Results in Mice May Help Shape Clinical Trial for NPC

In an article by Amy Dockser Marcus, the Wall Street Journal's Health Blog reported on a paper recently published in the Journal of Neuroscience on the use of cyclodextrin to treat NPC in mice. The paper's authors, led by Dr. John M. Dietschy of the University of Texas Southwestern Medical School, report that the treatment not only kept the mice alive, but prevented the cognitive decline of NPC.  

“It will be a very influential paper in the field,” scientist Daniel Ory [Chair of the NNPDF's Scientific Advisory Board] tells the Health Blog. Ory ought to know: he is the principal investigator on an NIH grant focused on getting cyclodextrin from the lab into NPC patients. He’s also working closely with NIH’s Therapeutics for Rare and Neglected Diseases program, which selected NPC and cyclodextrin as one of its pilot projects to attempt to repurpose drugs for use in rare diseases.

The NNPDF hosted a conference call on May 2 which addressed plans for an upcoming clinical trial using cyclodextrin in NPC patients. In addition to Dr. Ory, the conference call included information about the clinical trial from Dr. Forbes "Denny" Porter of the National Institutes of Health.  Text of the conference call (pdf).

WSJ Health Blog: Results in Mice May Help Shape Clinical Trial for Children with Rare Fatal Disease

[June 23, 2011 mem]


Doctor with child and its mother

NPC Research Updates Conference Call/Webinar
Includes Update on Planned Cyclodextrin Clinical Trial

The May 2nd recorded conference call/Webinar on NPC research updates is now available for those who were not able to participate, or for those who participated and would like to review the information presented. Please visit our special page for complete instructions for accessing the Webinar. Please note that the recording will be available for 30 days only.

Update:  A text document of the conference call is also available in PDF format. 

If you have a question for the presenters regarding the information on the recording, please submit it to the NNPDF Central Office and we will work to obtain the answers for you.

[May 6, 2011 mem]


FDA Grants Clearance for Experimental Intrathecal Administration of Cyclodextrin

The FDA has granted clearance of an Investigational New Drug (IND) application for administration of Hydroxypropyl Beta Cyclodextrin (cyclodextrin) into the central nervous systems of two patients with Niemann-Pick Disease Type C.   The cyclodextrin will be given intrathecally (into the space under the arachnoid membrane of the brain or spinal cord), first via lumbar injection, and then into the brain’s ventricle system.  Children’s Hospital & Research Center of Oakland, California, issued this press release.

The NNPDF would like to note the following regarding cyclodextrin:

  1. Cyclodextrin has shown promise as a potential therapeutic in animal trials.  However, issues of toxicity have also arisen.
  2. The NNPDF is aware that cyclodextrin is being used on a single-patient Investigational New Drug (IND) basis in the U.S. and in Brazil.
  3. More research is needed to understand issues related to drug delivery, efficacy and safety.
  4. The NNPDF will keep the NPC community apprised of developments regarding cyclodextrin.

Amy Dockser Marcus published this related article in her Wall Street Journal Health Blog on September 23.

[Sept 29, 2010 mem]


FDA grants “Orphan Drug Designation” to Cyclodextrin for treatment of Niemann-Pick Disease Type C

Due to the efforts of Hugh and Chris Hempel, Dr. Caroline Hastings and Ron Browne, an application to the Food and Drug Administration requesting “Orphan Drug Status” for Cyclodextrin has been approved. 

What exactly does that mean for our Niemann-Pick Disease community? 

Here is a bit of background and glossary that will help you to understand this latest development:

Orphan Drug Designation

An Orphan designation is a status granted to a drug if it meets two criteria:

1.  The drug is intended to treat a rare disease or condition.  Rare = less than 200,000 patients in the US with this condition.

2.  The drug shows “promise” to be able to treat the condition.  Promise can mean that the drug appears to have an effect in a test tube or an animal model (“preclinical”) or there may be some data in people that shows it might work.  This is not an assessment of whether the drug is effective or not, or is safe or not, only that it may work.

If a drug meets both of these conditions, per the assessment and review of the information by the Office of Orphan Product Development (OOPD), then the drug will be given an Orphan designation.  An Orphan designation provides predominantly financial incentives to the developer as described in the Orphan Drug Act. 

For example, one financial benefit for an Orphan-designated drug is that the developer does not have to pay a user fee when the developer submits a marketing application.  It is important to emphasize that an Orphan designation does not make any assessment at all on how the drug works in clinical trials, whether it is safe or effective in patients, nor whether it will ever be commercially available – the Orphan designation’s main purpose is to make the development of the drug more financially viable. 

To receive an Orphan drug designation, there is no requirement for any hard data, and not even a requirement for human data.

The benefits to the developer receiving an Orphan Drug designation include:

1) marketing exclusivity, which is “defended by the FDA” (perhaps even “better than a patent”)

2) freedom from filing fees --it typically costs $1.4 million to file a New Drug Application (NDA) with the FDA

3) tax credits of 50% on the costs of the clinical trials

Glossary

FDA approval:  An FDA approval is referring to whether the drug has received a marketing approval.  That is, an approved drug would be commercially available and a licensed physician could prescribe the drug.  This is an entirely separate issue from the Orphan designation, which again, provides financial incentives for drug development.         

Investigational Treatment:  In the US, clinical investigations with experimental drugs can only be performed under Investigational New Drug applications (INDs).  An experimental drug is defined as a drug that has not received marketing approval from the FDA and is not commercially available for the intended use.  A clinical investigation is defined as any experiment in which a drug is given to one or more patients.  That is, any use of a drug except for the use of a marketed (approved) drug in the course of medical practice. 

The process an experimental drug, Orphan or non-Orphan, must go through in order to obtain a marketing approval is complex and highly variable depending on many, many things.  It would not be possible to make even a reasonable estimate of a timeline or process outline for Orphan drugs in general, because this varies so greatly depending on the specific circumstances. 

Single Patient Investigational New Drug Application or "Compassionate Use"

"Single patient Investigational New Drug (IND) application" refers to the treatment of a seriously ill patient using a new, unapproved drug when no other treatments are available. Drugs that are being scientifically tested but have not yet been approved by the United States Food and Drug Administration (FDA) are called investigational drugs. Being permitted to use one of these drugs outside of a clinical trial specifically designed to study that drug may be commonly referred to as "compassionate use." 

"Compassionate use" is more properly termed "single patient Investigational New Drug (IND) application."

Single patient IND is very carefully regulated and the approval process to use such drugs for an alternate purpose is rigorous. The FDA has developed a patient- and family-friendly Web site that provides information about access to investigational drugs under several circumstances, as well as information that might help you make a decision about whether or not to seek access.

Remember that this information applies only to drugs that are considered investigational. If there is no current clinical trial and the drug is not approved for treatment of any condition, it would not fall under this approach to drug access.

The press release about the FDA Web site can be accessed at:

http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm176845.htm.

From the above page, there is a link to the actual site, or you can go directly to:

http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/AccesstoInvestigationalDrugs/default.htm

Another significant aspect of requesting single patient IND access to a drug is the ethical decision-making that parents, care givers and regulators must negotiate as they decide about an unapproved use of a drug. A recent article published in the Archives of Disease in Childhood entitled, “Compassionate and innovative treatments in children: a proposal for an ethical framework,” by Drs. Joe Brierley and Vic Larcher, outlines a series of questions that can be considered when deliberating about single patient IND use. Issues include potential for effectiveness, how to obtain informed consent, access to the drug by the patient population in question, and others.  Please see the full article (linked above, and here) for more details.

Additional Resources

There is additional information on the FDA Web site called FDA Basics that may be helpful in providing some background on drug development.     http://www.fda.gov/AboutFDA/Basics/ucm192696.htm

Click here for an article titled Drug Discovery, Development and Approval Process, outlining the process required for a drug to travel from the lab to patients in the U.S.

[Sept 30, 2010 mem]

Return to Caregiving Tips page

“The National Niemann-Pick Disease Foundation (NNPDF) does not engage in the practice of medicine. It is not a medical authority nor does it claim to have medical knowledge. This site is an educational service of the National Niemann-Pick Disease Foundation and is not meant to provide diagnostic or treatment advice. Information contained or suggested on this Web site does not constitute medical advice. For all information related to care, medication or treatment, the NNPDF recommends consulting a physician to determine if information presented is applicable. Please review these additional cautions about medical information provided on the Internet.”