Cyclodextrin for Niemann-Pick Type C

Chris and Hugh Hempel, parents of twin girls with an extremely rare and fatal genetic disease, are suing the rare disease therapy accelerator Cydan and the biotech companies Vtesse and Sucampo Pharmaceuticals for alleged breach of contract, unjust enrichment, and misappropriation of trade secrets.

The suit, filed in United States District Court in Nevada Friday, comes after Vtesse was purchased by Sucampo for $200 million in April, and Sucampo struck a December deal to be sold to Mallinckrodt Pharmaceuticals for $1.2 billion. It centers around cyclodextrin, which Vtesse calls VTX-270, and which is being tested as a treatment for Niemann-Pick Type C, a rare disease. “A massive fraud has been perpetrated not only against the twins and our family but our researchers, doctors, hospitals, donors and community,” Chris Hempel wrote on Facebook in August. “Cyclodextrin has been stolen and now sold for $200 million dollars!! It’s going to a billion++ dollars when approved. This was a drug funded and created by all of you who helped us.”

The Hempels are filing on behalf of their daughters Addison and Cassidy, who were diagnosed with Niemann-Pick Type C when they were toddlers. The girls had enlarged spleens, one of the many symptoms of Niemann-Pick Type C that also include movement problems, developmental delays, seizures, and hearing loss. Cells in the girls’ bodies don’t metabolize and transport cholesterol properly, which leads to buildup in the liver, spleen, and brain. The disease is an ultra-rare genetic condition with only an estimated 500 diagnosed cases worldwide. There is no cure.

Soon after getting the diagnosis, the Hempels started pursuing cyclodextrin, a sugary compound, as a potential treatment based on the research of scientist Benny Liu while he was at the University of Texas Southwestern Medical Center. Along the way, they’ve grabbed plenty of press attention. The early story of the Hempel’s pursuit of cyclodextrin and other efforts to develop drugs for Niemann-Pick Type C at the National Institutes of Health were previously reported in The Wall Street Journal by Amy Dockser Marcus after she followed the parents, scientists, and children for six years. In 2014, they were profiled on Dr. Sanjay Gupta’s CNN show Vital Signs. “We were willing to do anything and take that risk,” Chris Hempel said in the segment. “And, you know, without risk, there’s no reward.”

The Hempels say they bought cyclodextrin, which is an ingredient in household products like Febreze and used in the formulation of some drugs to make them useful in the body, from a distributor.  At first, they gave the girls cyclodextrin dissolved in water in their sippy cups. Later, the Hempels sought FDA permission to give the girls weekly IV infusions of the compound, then intrathecal injections through spinal taps every two weeks, then infusions through catheters that gave direct access to the brain. They convinced Johnson & Johnson to share safety research on cyclodextrin, which the company used in an antifungal medicine, and developed treatment protocols with the girls’ doctor, collecting safety data all the while.

As researchers associated with the National Center for Advancing Translational Sciences, a division of the NIH, began clinical trials of cyclodextrin in children with Niemann-Pick Type C, the Hempel’s lawsuit says they asked to reference data on the Hempel twins’ treatment, which their parents and doctor allowed. That data is at the center of the lawsuit. The Hempels allege that the data was provided to a doctor treating a patient in the NIH trial for one-time use, but instead was used to inform Vtesse’s clinical trials. The Hempels say they had intended to create a non-profit to develop cyclodextrin, and that they had conversations with Cydan, a biotech incubator, to do so. But they allege that Cydan instead used that information to help start Vtesse.

It doesn’t appear that the Hempels possessed any patents protecting this use of cyclodextrin. They are alleging breach of contract. They also appear to have had data from only their daughters, although this included information on how best to dose cyclodextrin, including how to inject the drug directly into the spinal column. Caroline Hastings, the doctor at UCSF Benioff Children’s Hospital who treated the Hempel twins, is not a party to the lawsuit and says she has no financial relationship with the Hempels or the company they were trying to form. But she says she found the way data she shared was used to be irregular.

“I have to say we all feel pretty shafted by what happened,” Hastings says. “And it’s divided the patient community. With rare diseases, you want people to come together. It’s been divisive having multiple groups.” She later added: “I’ve never personally had an experience like this in my 25 years of doing clinical trials.”

The press release announcing the Sucampo-Mallinckrodt deal says they expect to file a new drug application for VTS-270 in 2018 for anticipated approval in 2019. Its estimated peak net sales are greater than $150 million. Approval of the drug for a rare pediatric disease would also award Mallinckrodt a priority review voucher, which it could use for a drug application of its own or sell.

The Hempels say their plan was to direct half of the profits from commercializing cyclodextrin into more research on treatments for Niemann-Pick Type C and to help families affected by the disease. In the lawsuit they express concern about losing control of future cyclodextrin research and the drug’s price.

“In short,” the Hempels allege in the lawsuit, “Cydan, Vtesse, and Sucampo had not only misappropriated the Hempels’ Confidential Information and trade secrets, but also the [Niemann-Pick Type C] community’s autonomy.”

“While we cannot comment on active litigation, we will defend our position vigorously,” Peter Greenleaf, Sucampo’s Chairman and CEO, said in a statement. “We are pleased that Sucampo has been able to play an active role in advancing the science around this potential treatment for Niemann-Pick Disease Type C with the scientific rigor that a clinical trial demands – all in efforts to benefit the patients and families living with this devastating, fatal disease for which there is no approved therapy in the U.S.”

“We cannot provide specific comment on ongoing litigation, but believe their claims are without merit and plan to vigorously defend ourselves,” Cydan said in a statement. “Cydan is committed to improving the lives of patients living with rare monogenetic diseases, such as NPC. We are pleased we were able to play a role in advancing VTS- 270, a potentially meaningful new treatment for patients and families living with this devastating, fatal disease, for which there are no currently approved treatment options in the U.S.”

https://www.forbes.com/sites/elliekincaid/2018/01/08/mother-alleges-biotech-firm-stole-data-from-her-sick-children/amp/

Courtesy of a colleague

See:  http://childnervoussystem.blogspot.com/2018/03/elizabeth-berry-kravis-jamie-chin-anne.html
https://childnervoussystem.blogspot.com/2017/10/intrathecal-2-hydroxypropyl.html