FDA Green Lights Phase 2 Trial of NNZ-2591 in Children With PWS
Neuren Pharmaceuticals therapy aims to improve brain cell communication
Neuren Pharmaceuticals will test its therapeutic candidate NNZ-2591 in children with Prader-Willi syndrome (PWS) in a new Phase 2 clinical trial, the company announced in a press release.
The U.S. Food and Drug Administration (FDA) gave Neuren the go-ahead to conduct the trial following the company’s submission in December of an investigational new drug application for the therapy’s use in PWS.
NNZ-2591 is being developed for serious neurological disorders that manifest in early childhood. To date, this includes PWS and Angelman, Phelan-McDermid, and Pitt Hopkins syndromes. None of these diseases have an approved treatment, according to Neuren.
While no details of the planned trial have yet been released, Phase 2 studies of NNZ-2591 in Angelman, Phelan-McDermid, and Pitt Hopkins are underway.
Common to all of these disorders is impaired communication between nerve cells, leading to disrupted brain function that significantly influences daily life.
Neuren Pharmaceuticals targeting early childhood disorders
In recognition of an “urgent unmet need,” the FDA has granted NNZ-2591 orphan drug status for all four of the disorders it is targeting, Neuren reported in the press release. Orphan designation provides regulatory support to help speed the development of treatments for rare diseases.
NNZ-2591 is a lab-made version of cyclic glycine proline (CGP), a naturally-occurring protein that can regulate the signaling of insulin-like growth factor 1 (IGF-1).
IGF-1 is a hormone that plays an important role in metabolism and growth. In the brain, it’s produced by nerve cells, where it aids in proper brain development. Research has shown that PWS patients exhibit IGF-1 deficiencies in the bloodstream at a young age.
Neuren believes its therapy may help restore more normal communication between brain cells in neurodevelopmental diseases such as PWS.
NNZ-2591 also is “state-dependent,” meaning it will only modulate IGF-1 signaling in impaired cells, but doesn’t impact normally functioning ones, the company says.
In preclinical studies, six weeks of NNZ-2591 treatment led to the normalization of all behavioral deficits in a mouse model of PWS. This included cognitive problems, low activity levels, anxiety, and social deficits.
Moreover, fat mass, insulin levels, and IGF-1 levels all were normalized in mice given a high-dose treatment, and were partially normalized in mice given a low dose.
A Phase 1 clinical trial (NCT04379869) evaluated the safety and tolerability of single and multiple doses of NNZ-2591 in 28 healthy volunteers.
The treatment was safe and well-tolerated in Phase 1 testing, according to Neuren. It also has shown good absorption into the bloodstream after oral administration and was able to reach the brain.
The three ongoing Phase 2 trials all are designed in the same way, with the goal of preparing for Phase 3 trials as efficiently as possible.
In each, up to 20 children undergo an observation period for four weeks (about one month) before starting twice daily treatment with NNZ-2591 — delivered as an oral solution — for 13 weeks.
For the first six weeks of treatment, the dose of NNZ-2591 is titrated up to its target dose, which is then maintained for the remaining treatment window. The trials will end with a two-week follow-up period.
No other diseases are listed in the pipeline for this therapy, but Neuren noted in an investor presentation that there are “many other neurodevelopmental disorders potentially relevant for NNZ-2591.”
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