Neuren Pharmaceutical’s NNZ-2591 Wins FDA’s Orphan Drug Designation to Treat Angelman

The U.S. Food and Drug Administration (FDA) has granted orphan drug status to candidate therapy NNZ-2591 to treat Angelman syndrome and two other childhood neurodevelopmental disorders for which there are no currently approved medications.

Neuren Pharmaceuticals, the company that develops the therapy, submitted the applications to the FDA in July 2019. Orphan drug status aims to encourage therapies for rare and serious diseases, through benefits such as seven years of market exclusivity and exemption from FDA application fees.

“Orphan Drug Designation is an important commercial milestone which adds significant value and momentum in respect of our plans to move NNZ-2591 into clinical trials in 2020,” Richard Treagus, Neuren’s executive chairman, said in a press release.

The company now plans to initiate a Phase 2 clinical study in the second half of 2020.

NNZ-2591 is an analogue of a small protein (peptide) called cyclic glycine proline (cGP), which naturally exists in the brain and is important for the development of neurons. Treatment with NNZ-2591 aims to restore the normal connectivity and signaling between brain cells.

Preclinical studies with multiple animal models, including fragile X syndrome, Parkinson’s disease, and multiple sclerosis, have shown that NNZ-2591 has neuroprotective and memory-enhancing effects.

The therapy also showed positive effects in a mouse model of Angelman syndrome. Treatment for six weeks lessened mice deficits in tests that measured their levels of anxiety and sociability. Moreover, NNZ-2591 restored mice motor performance and cognition to normal levels, while eliminating seizures.

Positive results with NNZ-2591 also were observed in preclinical models of two other diseases, Pitt Hopkins syndrome and Phelan-McDermid syndrome. NNZ-2591 also has been granted orphan drug status for treating these neurodevelopmental disorders.

Both of these conditions also are caused by mutations in single genes, and like Angelman, are characterized by intellectual disability and developmental delay. Pitt Hopkins is caused by problems in the TCF4  gene, while Phelan-McDermid is caused by mutations in the SHANK3 gene.

“This confirms that NNZ-2591 is a valuable asset for Neuren and validates the encouraging preclinical data as well as our plans to develop NNZ-2591 in parallel for these three debilitating childhood disorders with urgent unmet need,” Treagus said.

“We look forward to working with the FDA as we execute on our development plans,” he added.