Join us in the Fight Against Niemann-Pick Type C Disease
January 23, 2013
NIH Clinical Trial Begins
A clinical trial to evaluate a drug candidate called cyclodextrin as a possible treatment for Niemann-Pick disease type C1 (NPC), a rare and fatal genetic disease, will start today, researchers announced. Scientists from the NIH’s National Center for Advancing Translational Sciences (NCATS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) will conduct the clinical trial at the NIH Clinical Center. Reaching this trial stage required collaboration among government, industry, patient advocacy groups and academic researchers.
January 4, 2013
Update on HPBCD Trial
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
Forbes D. Porter, MD, PhD
Cyclodextrin Clinical Trial Protocol
We are pleased to inform the NPC Community of an upcoming clinical trial at the NIH. This trial, which will study the safety of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in Niemann-Pick disease, type C1, is in the process of being reviewed by the FDA. We are hopeful that we will be able to start enrolling patients in January 2013.
Press Release November 30, 2012
Researchers collaborate to seek FDA approval for drug treatment for rare disease.
Gene Stowe and Marissa Gebhard
Notre Dame alumnus Norbert Wiech has founded Lysomics, LLC to manage the clinical development needed to bring to market a promising new treatment for people with Niemann-Pick Type C (NPC) disease. FDA support is being sought for early clinical exploration of an approved drug to fight this rare disease that has no cure or treatment.
Lysomics is based on the work of Notre Dame professors of chemistry and biochemistry Olaf Wiest and Paul Helquist, and Frederick Maxfield at Cornell University's Weill School of Medicine to find treatments for NPC. NPC disease is a rare, fatal neurodegenerative disease that primarily strikes children before and during adolescence.
With support from the Ara Parseghian Medical Research Foundation, researchers from Notre Dame and Cornell University have demonstrated the effectiveness of small molecule histone deacetylase inhibitors (HDACi) in correcting the NPC phenotype in human patient cells by increasing expression of the NPC1protein. Wiech, who has started similar successful companies in the past, founded Lysomics to shepherd the drug, vorinostat, through the FDA process.
The group is focusing on vorinostat, an FDA-approved anti-cancer treatment. Lysomics, which is seeking FDA approval to repurpose vorinostat to treat NPC, will soon submit an Investigational New Drug application. The existing FDA approval of this drug has previously established its safety in humans and means that several expensive steps are not required. Initial clinical trials could start next year. Lysomics is considering clinical collaborations with the National Institutes of Health and other clinical centers for the Phase 1 trials.
NPC, a genetic, degenerative neurological disease, affects fewer than 100 people in the United States, and an estimated 20-40 are in the early stage of the disease who could benefit from the treatment. Most patients die by the age of 16, and few survive beyond 25. The disorder prevents their bodies from processing cholesterol which accumulates in the brain. Vorinostat is most effective in the early stages of NPC, although it could improve quality of life for older patients.
The effort will benefit from the 30-year-old Orphan Drug Act that helps development of treatments for conditions that affect fewer than 200,000 people. The federal law grants exclusive marketing for seven years after FDA approval, tax credits of 40 percent for clinical research expenses, grants for studies up to $200,000 a year for three years, and a waiver of a high filing fee.
“Lysomics from the onset was a not-for-profit operation,” said Wiech, the company’s CEO. “You can’t get a drug approval unless you’re a company. A company has to be structured, so it can handle the data, and do all the piles of paperwork that are required to go through this.” After approval, the drug will need no marketing because parents of children with NPC will be eager for access to the treatment,” he said.
Contact: Paul Helquist, (574) 631-7822, firstname.lastname@example.org
Update on FDA Approval of Cyclodextrin Clinical Trial
December 15, 2011
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 Therapeutics for Rare and Neglected Diseases Team
From the Heart of NP-C Researchers
For the many researchers who have dedicated their lives to solving the mystery of Niemann-Pick Type C disease and to finding a treatment and cure, NP-C is not simply an interesting scientific problem.
These caring and brilliant scientists, many of whom are parents themselves, feel a deep pain and sorrow each time they receive news that another young person afflicted with NP-C has passed away. Each has a dream to find the answer to NP-C which will lead to a treatment as quickly as possible.
The following are excerpts from a few of our researchers who have expressed their feelings in this regard:
Steven Walkley, DVM, Ph.D., Albert Einstein College of Medicine, NY-"I have been involved in the study of storage diseases, including NP-C, for many years and have had the privilege of getting to know a number of families with an affected child, in some cases more than one. As the father of two young children, I readily identify with these parents. Time and time again, the greatest impact for me has been to get to know the mothers of affected kids. What I have come to believe is that there is nothing in this world more powerful, or more courageous, or more enduring, than a mother's love."
David Marks, Ph.D., Mayo Clinic, MN-"As a parent, the connection I feel with the Parseghians and other affected NP-C families has touched me and brought me to tears many times. Receiving funds to work on NP-C, I bring back to the lab a commitment that our job is not just to study an interesting disease, but to make progress in a race against time with the goal of hopefully contributing to saving lives."
Robert Erickson, M.D., University of Arizona, AZ-"I have been a medical researcher for 44 years. Seven years ago when I met Cindy and Mike Parseghian and their children, I became emotionally involved with my research in a new way."
Steve Sturley, Ph.D., Columbia University, NY-"A day doesn't go by when I don't ask myself what more can be done to understand and cure this genetic disorder. When I look at what the Parseghians and the other affected families do each day, and as my own family builds, I just hope I would have the same courage and determination in the same situation."
Elina Ikonen, M.D., Ph.D., National Public Health Institute, Finland-"When I have taken the trip to Tucson to the APMRF annual NP-C Scientific Meeting, I have told my daughters, 'There are two little girls in Arizona that need my help." When Christa passed away, I told Satu and Sonja about that and they asked, 'Mom. Why didn't you help her after all?' I replied, 'I did my best but sometimes that is not enough. But that does not mean we should give up. We will just have to keep working and one day we will succeed.'"
Peter Pentchev, Ph.D., Retired, National Institutes of Health-"The parents of NP-C children take the lead in setting the example of how the scientific community should act. Their love, courage and devotion have certainly inspired many scientists to move beyond the arena of competitive research to establish a common meeting ground where the heart as well as the mind dictate their action."