Denali touts two-year neurofilament biomarker data for Hunter syndrome asset

Denali Therapeutics once again touted biomarker data for its experimental Hunter syndrome drug Tuesday morning, aiming to push the program toward FDA approval after disappointing Wall Street two years ago.

The biotech revealed that 13 patients who had received the drug, dubbed DNL310, for at least two years saw an average 64% reduction in serum neurofilament. Additionally, in 11 evaluable patients at the two-year mark, Denali observed an average 53.5% reduction in cerebrospinal fluid neurofilament.

Both figures came in statistically significant compared to baseline levels, with the serum number reaching a p-value of p<0.001 and the CSF reduction reaching p=0.011, Denali said in a webinar Tuesday morning. Statistical significance in serum was first reached at 61 weeks when the reduction was measured at roughly 40% below baseline.

The results come from an open-label Phase I/II study and open-label extension looking at DNL310 in children with Hunter syndrome — as of March 2, 27 patients had completed the 24-week study period.

Denali shares $DNLI ticked upward about 5% in pre-market trading after the announcement.

Neurofilaments are proteins that function as the cellular infrastructure of neurons, linking them to one another like cables. When neurons are damaged, be it from a head injury or disease, neurofilaments can leak into the bloodstream and cerebrospinal fluid.

Researchers have increasingly sought to use the presence of neurofilament in these fluids as a surrogate biomarker for different neurodegenerative diseases like ALS and Alzheimer’s. Biogen recently received accelerated approval for its familial ALS drug Qalsody based on its effect on lowering plasma neurofilament, which regulators deemed adequate to predict a clinical benefit.

Whether lowering neurofilament can impact the course of other diseases remains an open question. It’s a question, however, with huge ramifications for biopharma companies focusing on this research.

Tuesday’s data come after Denali initially disappointed investors and analysts in July 2021, when DNL310’s first in-human results proved inconclusive in neurofilament. At the time, the biotech reported that, in five patients, average serum neurofilament increased by 15% and average CSF neurofilament increased by 36% after 24 weeks.

How exactly the new data will impact DNL310’s chances at approval remain unclear, though in its release Tuesday, Denali said the FDA had recommended NfL as an exploratory endpoint in Hunter syndrome. The drug is still being tested in a larger, Phase II/III trial, and Denali intends to use data from both studies in any eventual application.

Carole Ho

The company is also positioning a different biomarker, known as heparan sulfate, as the “primary” biomarker for a potential BLA, CEO Ryan Watts said during the webinar. Heparan sulfate levels are highly elevated in Hunter syndrome patients, and DNL310’s objective is to restore lost enzyme function and return such levels to normal.

But neurofilament remained the focus of analyst questions during Tuesday’s webinar, given the recent Biogen approval. In response to a question about accelerated approval for DNL310, Denali chief medical officer Carole Ho said discussions about that pathway remain ongoing. But if that path opens up for Hunter syndrome, Ho said that “certainly we will proceed.”

Denali also expects to present more data at a conference later this summer detailing how the lowering of neurofilament can impact the course of Hunter syndrome, Ho said.

therapeutics
medical
biotech
fda
research
shares
trading