* Update, July 18, 4:30 pm: The Hempel twins Addi and Cassi died on July 4th. They were 15 years old. "They died within minutes, and we're full of grief," wrote her mother, Chris Hempel, in an email to Science Insider.
She wrote that her daughters had been admitted on June 29 and 30 at the Renown Regional Medical Center in Reno, Nevada, after developing respiratory distress and high temperatures. It turned out that the cause was an aggressive virus that had invaded her lungs. Although Niemann-Pick Type C (NPC) was not included in their death reports, "the underlying NPC disease certainly contributed," wrote Hempel. "[T] Heirs of pulmonary systems have already been weakened by the NPC."
Hempel and her husband, Hugh, pioneered the experimental use of a sugar molecule, 2-hydroxypropyl-β-cyclodextrin, to treat the rare genetic disease and obtained a compassionate use approval from the US Food and Drug Administration for use twins. In January 2018, they sued several companies involved in the development of commercial treatment. Their allegations include breach of contract, theft of trade secrets and unjust enrichment. The Hempels attorney filed a motion to defer the lawsuit at the US District Court in Maryland on July 11 to stamp out Hempel's time. But Chris Hempel wrote that they intend to move forward "energetically" with this lawsuit.
Here's our previous story from November 9, 2018:
A treatment for Niemann-Pick Type C (NPC), an extremely rare and ultimately The study of 56 children and adolescents whose main sponsor had announced on Tuesday showed that a fatal neurodegenerative disease was no different than a placebo. It is surprising, however, that the disease did not progress in either the treatment or the placebo group during the one-year study. Usually, the condition that results from disturbed cholesterol metabolism is inexorably deteriorating, leading to balance disorders, dysphagia, seizures and cognitive disabilities.
The drug VTS-270, a donut-shaped sugar molecule called cyclodextrin. showed no statistically significant segregation of placebo, "said Steven Romano, vice chairman and scientific director of Mallinckrodt Pharmaceuticals, to investors in a conference call on Tuesday. "Importantly, neither [patients in the active or placebo arms of the trial] showed disease progression as expected in neurodegenerative disease over 52 weeks post-observation." The drug was administered by injection into the cerebrospinal fluid circulating in the brain.
News – and the way Mallinckrodt, whose US headquarters is located in St. Louis, Missouri, transmitted them – shocked families in the NPC community who learned of it when investors started, to tweet about it. (The company sent a letter to NPC disease groups on Tuesday.) Mallinckrodt, whose shares are publicly traded, added in a statement to Science that the securities act prevented the company from notifying patients earlier.)  Will Evans, a family physician in Leeds, UK, is chairman of the charity Niemann-Pick UK. His eleven-year-old son, Sam, was in an earlier study to determine a safe dose of the drug as well as in the most recent study. "Many families, including ours, have invested several precious years in this process – bringing our children to test sites every two weeks to undergo invasive procedures – and so much hope has been placed throughout the community for the results of this process "Evans says. "It's incredibly disappointing and hurtful for these families to hear this news about a financial call on Twitter. It has caused tremendous excitement for many families. "
" It's devastating news, "adds Chris Hempel of Reno, Nevada, whose twin daughters Addi and Cassi have compassionately received cyclodextrin injections for 14, 8 years. Use basis approved by the US Food and Drug Administration (FDA). She says the treatment helped her daughters regain their hearing and stabilize swallowing, although other symptoms worsened. "As we know from personal experience and the experience of others in the community, there are children who respond to cyclodextrin treatment. Obviously, recent results are confusing and raise many questions regarding the structure of the clinical trial. Some researchers investigating extremely rare diseases such as NPC say the results of the study suggest that using conventional double-blind, randomized controlled trials might be inappropriate for such conditions, resulting in too difficult-to-interpret results such as current leads. The difficulty of patient recruitment, they say, could prevent conventional studies from having sufficient statistical power to achieve predefined statistical significance, even if the experimental tool is actually effective.
Marc Patterson, a pediatric neurologist at the Mayo Clinic in Rochester, Minnesota, who has been conducting NPC research for 30 years and looks after NPC children, says, "This is a disappointing but very important result. The question I have is: Is it really true that this remedy is not effective, or is it the result of an attempt that might have been better in retrospect?
Patterson argues that the drug has shown positive results In mouse and cat models, the disease may be effective in some children, but not in others, and factors such as the duration of the current study – one year in the course of a disease progressing slowly can – could mask such achievements. He also argues that the FDA should consider setting a different "benchmark" for evaluating therapies for extremely rare, individually variable diseases such as NPC, such as determining the efficacy of a particular child by comparing disease progression during the study with the same child's rate to determine progression before starting the drug.
Romano told investors that the company was expecting both children who received spinal injections of the drug every two weeks for a year, as well as children who received sham-spot injections – one-third of those in the study with 56 patients would worsen during the trial, but the children who received the drug would worsen more slowly. The Company is examining "the entirety of the data we have" to understand if and how the drug could still deliver results that would be FDA-approved. For example, the company will examine data from a so-called "large number" of individual patients who have been treated with FDA compassionate use programs. And it will take into account data from an ongoing, open phase of the study, in which all patients who have participated and wish to continue receiving drug injections.
Label the patients treated and determine if there are any gradual differences over the course of this additional treatment. "
VTS-270 was one of the most promising drugs served by the National Center for the Advancement of Translational Sciences (NCATS), part of the National Institutes of Health (NIH) in Bethesda, Maryland. NCATS partnered with Vtesse, a biotechnology company in Gaithersburg, Maryland, to fund the drug for a first clinical trial at the NIH Clinical Center. When Vtesse relocated the drug to the new, pivotal study less than two years later, the center pointed to the rapid progress of the drug as a "tremendous benefit" to patients – an example of how the US biomedical agency can use drugs in develop their earliest stages until they are adopted by the industry.
In March 2017, privately held Vtesse was acquired for $ 200 million by global biopharmaceutical company Sucampo Pharmaceuticals. Eight months later, last December, Sucampo was acquired by Mallinckrodt for $ 1.2 billion in cash. Mallinckrodt's press release states that the acquisition includes "strengthening our rare disease pipeline with VTS-270".