Notre Dame spinoff illustrates the endless hurdles in rare disease drug development

Lysomics founder Norb Wiech with students.

Ara Parseghian is most known for his 11-year run as coach of the University of Notre Dame football team, which went 95-17-4 while he was coach and won two national championships. But in his post-football life, Parseghian has created a legacy even more meaningful.

The former coach (and former Cleveland Browns player) founded the Ara Parseghian Medical Research Foundation, which supports work toward a cure for Niemann-Pick Type C, a lethal neurodegenerative disease that struck his three youngest grandchildren.

The rare disease is caused by genetic mutations that make the body unable to transport cholesterol and other lipids in and out of cells properly, which results in a buildup of lipids in the liver and the brain that initiate neurodegenerative processes.


There are currently no treatments for the disease in the U.S. Actelion Pharmaceuticals’ drug Zavesca is approved in Canada and Europe to slow the progression of Type C, but it was rejected by the U.S. Food and Drug Administration in 2010 with the request for more data.

The foundation has brought awareness to the disease and has inspired collaborative work among several universities including Notre Dame, said Norb Wiech, the founder of Lysomics LLC.

Wiech, himself a Notre Dame alumnus, founded Lysomics in 2010 to bring some of that research out of the lab and into the clinic. The startup is developing a treatment based on the work of Notre Dame researchers Olaf Wiest and Paul Helquist, and Frederick Maxfield of Cornell University’s Weill Medical College. They identified a class of compounds called histone deacetylase inhibitors that demonstrated the ability to correct the cholesterol issue in the lab.

Lysomics is commercializing an FDA-approved small molecule anticancer drug in that class called vorinostat (marketed by Merck under the name Zolinza) for treatment of NP. Wiech has met with the FDA and is doing preparation work for an Investigational New Drug application. According to Notre Dame, clinical trials could start as early as next year.

That is if the company can find funding. Orphan drug development is so challenging because, while the National Institutes of Health and foundations will fund discovery research, the next stage is not an academic exercise. “That’s one of the big gaps for some of these diseases: they’re so small that companies can’t find any sponsors because people aren’t sure it will be able to recover their money,” Wiech said.

The trials won’t be that expensive, relatively speaking, because they will be so small (the total number of children with Type C in the U.S. is estimated to be less than 200). And because the drug has been through clinical trials and has already been used in a small number of pediatric patients, Lysomics will be able to save about a year’s time by starting in late phase 1/early phase 2. So, Wiech said he thinks benefactors and angel investors, not VCs and Big Pharma companies, are the most likely targets for funding.

Then there’s the issue of what the drug will actually be able to do. A true cure for NP would involve gene therapy and the reversal of neurological damage, which researchers aren’t yet able to do. But if the treatment were given to patients at an early enough stage, Wiech thinks the drug could slow or stop the progression of the neurodegeneration and improve the quality of life for the patient and the parents.

That brings up another challenge. In the most quickly progressing cases, the first signs of neurological damage become apparent in early childhood. These are the children who could most benefit from the drug. “Starting a drug treatment at such an early age is really a quandary for FDA […] because it’s an age when the body is growing rapidly and any drug could interfere with growth,” Wiech said. So the FDA is very cautious — and rightfully so. “I think there’s a tremendous awareness of respect to the patient,” he said.

So he’s working carefully to iron out the design of the clinical trial, working with the FDA to determine the best endpoints to measure and how to best work within the guidelines to demonstrate safety with such a small population of patients.

“In part, the degree of rareness is because it’s so lethal,” Wiech explained. “Ninety percent of those who have it do not live beyond their teenage years.”

[Photo from Notre Dame newswire]

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