Allievex launches with Pappas cash and rare disease drug from BioMarin
In July 2015, BioMarin began a series of trials for a drug targeting a rare and fatal childhood disease that had remained virtually unchanged since its 1963 discovery. Now, with their lead candidate entering Phase II, they’re handing it off to a new company out of Pappas Capital: Allievex.
Backed by Pappas and Novo Holdings, Allievex will tackle Sanfilippo Syndrome type B, a lysosomal neurological condition for which no treatment exists. Allievex CEO Thomas Mathers indicated to Endpoints News that the new company would broadly focus on childhood conditions but begin with Sanfilippo and the BioMarin treatment:
“Tralesinidase alfa may be the first disease modifying therapy which could provide cognitive stabilization or growth, as well as potentially impact hearing, sleep, bowel habits and overall quality of life for Sanfilippo B children,” Mathers wrote Endpts in an email. “The FDA recently issued a draft guidance for industry which we believe directly speaks to Sanfilippo B, and we believe that this Guidance provides Allievex a clear road map to register tralesinidase alfa.”
Allievex and its partners, though, have not disclosed how much funding they’re getting. The FDA guidance is a July 2018 document detailing evidence standards for drugs aimed at enzyme-based, rare, slow-progressing diseases.
Tralesinidase alfa is a form of enzyme replacement therapy, a type of treatment used primarily in other lysosomal diseases — diseases that arise from disabling mutations in the enzyme-containing sacs found inside cells. In Sanfilippo, the cells can’t degrade a sugar called heparan sulfate, which accumulates and eventually kills neurons and other organ cells.
The slow buildup gives the disease a particularly agonizing arc: healthy development into around age two, when cognitive skills and sensory function can begin to decline rapidly. Most die in their teens. The second most common form of the disease, Sanfilippo B, affects about 1 in every 200,000 people.
In the therapy, scientists create a recombinant form of the missing enzyme — alpha-N-acetylglucosaminidase or NAGLU — and inject it directly into brain ventricles through a specialized catheter, ideally degrading the heparan sulfate and stemming the degradation of cells. The enzymes have to be injected into the brain because otherwise, they will not cross the blood-brain barrier.
BioMarin has completed an observational study and recently began a Phase II study.
Allievex won’t be the first company to try enzyme therapy on Sanfilippo B. Alexion spent $8.4 billion to acquire Synageva in 2015, primarily to acquire Kanuma but in part for SBC-103, a recombinant form of NAGLU. They saw some early positive results but shelved the drug in 2017.
A 2015 review of the disease in Dove Medical Press, noted that in animals — the BioMarin Phase I/II clinical trials had yet to begin — enzyme injection into the brain “has been successful in alleviating a number of symptoms but has also emphasized the importance of early detection on account of the irreversibility of certain (particularly neurodegenerative) aspects of the pathophysiology.”
Abeona is also working on a form of gene therapy for Sanfilippo A, now in Phase I/II, but that has limited implications for other forms of the disease. Although Sanfilippo A, B, C, and D manifest in similar ways, they differ in their genetic foundations.