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).
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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
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Follow this link to read the November 4th, 2011, announcement: Cyclodextrin Trial Update 11-4-11 |
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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) [Nov.4, 2011 nmh] |
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Wall Street Journal Health Blog Article: |
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]
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NPC Research Updates Conference Call/Webinar |
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:
- Cyclodextrin has shown promise as a potential therapeutic in animal trials. However, issues of toxicity have also arisen.
- 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.
- More research is needed to understand issues related to drug delivery, efficacy and safety.
- 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:
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]
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