Rare Disease Report

Conversation with CEO of Vtesse about Niemann-Pick Type C

JULY 31, 2016
James Radke, PhD
Niemann-Pick type C is a progressive, irreversible, and ultimately lethal genetic disease. It is caused by a defect in lipid transportation within the cell, which leads to excessive accumulation of lipids in the brain, liver and spleen.
Recently, Vtesse announced they had secured $17 million in additional funding to support their ongoing pivotal clinical trial of VTS-270 for treating Niemann-Pick type C1 disease. We talked to the CEO of Vtesse, Ben Machielse, about the study and the horrific impact this disease can have on a family.
RDR: Can you briefly describe Niemann-Pick type C disease?
Machielse: Niemann-Pick type C is a neurodegenerative disease but there’s also some visceral involvement where the body is not able to breakdown intracellular cholesterol and cholesterol accumulates in the cells and reaches levels which become toxic to the cells and ultimately the cell will die.
A child with Niemann-Pick type C is frequently born almost normal but by the age of 4 to 6, parents start to notice that the child’s cognitive abilities are not progressing as expected. Also, there are motor skill issues such as tripping and those kind of things. Parents often embark on a pretty difficult path to get diagnosed Niemann-Pick type C because it’s not that well known. It can take up to 2 years for a child to be diagnosed with the disease. However, the disease will progress and ultimately it will lead to the child being paralyzed, severely hampered cognitive abilities, and, on average, the children die at the age of 16 or 17. So it’s a very, very severe disease. It’s an absolutely horrible disease.
RDR: Why so long to diagnose? 
 Machielse: Partly because of the rarity. Only 500 or 600 children have the disease. Also, one of the most difficult things with the Niemann-Pick type C is that the disease onset and the disease progression is highly, highly variable. And it affects a number of disease domains. It affects fine motor skills, ambulation, coordination, swallowing, hearing, eye movement. And it is almost impossible to predict what of those things have started to develop first. So, if someone comes in with cognitive problems, people don’t necessarily think Niemann-Pick. And so from a what’s called symptomatology point of view, it is very difficult to diagnose the disease, and then of course in combination with the rare aspect. And as I said before, it sometimes takes up to 2 years for a child to be diagnosed with Niemann-Pick type C.
RDR: How is the disease currently managed?
Machielse: There is not much. There’s a drug called miglustat, which is not approved in the US but is approved in many other countries, and may be used off-label here in the US. It has some modest effect on the disease but not really a substantial effect. That’s at least what we hear from the field.


VTS-270 or hydroxypropyl-β-cyclodextrin targets cholesterol storage. Preliminary in-vitro and animal studies have demonstrated that it helps cholesterol bypass the NPC1/NPC2 pathway, promoting transport of the cholesterol that would normally accumulate in the lysosomes of cells that have the NPC1 or NPC2 mutation. This process restores the cell’s normal cholesterol metabolism and regulation.
Recently, Vtesse announced a phase 2b/3 study in underway to test the efficacy and safety of VTS-270 in children with Niemann-Pick type C
The ongoing Phase 2b/3 study is a prospective, randomized, double-blind, sham-controlled trial. It is a three-part efficacy and safety trial of VTS-270, administered by the intrathecal route every two weeks, with planned enrollment of approximately 51 patients.
In May, Vtesse announced completion of the dose-finding portion of the clinical trial and selection of a dose level (900 mg) for further testing in the patients to be enrolled for the remainder of the trial.
Prior to that, the company presented results of a Phase 1/2 study at the 2016 WorldSymposium in San Diego, CA that showed disease progression was reduced by about 60% compared to a matched natural history study control group.
RDR: Can you describe the Phase 2b/3 study
Machielse: We are currently in a phase 3 clinical trial and where we administer the drug every two weeks through a lumbar puncture, and that way we believe we only hope that we can affect the neurological aspects of the disease positively. We have done a phase I study together with NIH, and that study had very encouraging results, suggests that there is a possibility that our drug stabilizes the disease. Of course, that needs to be confirmed in the phase 3 trial. We are quite encouraged that there is a possibility that this drug has a substantial positive impact on the lives of children with that disease.
We have shared some initial results of that study where we selected the dose, so we have done a safety and tolerability study of the dose for the study and that has been completed. And now we are in enrolling the remainder of the study. And we hope to actually be in a position that in Q3 of next year, we can read out the study and talk about the results.
For more information a bout the Phase 2b/3 clinical trial, including the current list of participating study sites, visit www.theNPCstudy.com.

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