Tetra Discovery Partners announced that the FDA had given its Investigational New Drug application the go-ahead for Fragile X Syndrome and potentially other autism spectrum disorders.
Grand Rapids, Michigan-based Tetra Discovery Partners announced that the U.S. Food and Drug Administration (FDA) had given its Investigational New Drug application (IND) for BPN14770 the go-ahead for Fragile X Syndrome and potentially other autism spectrum disorders, as well as Alzheimer’s disease.
The company expects to begin a Phase II clinical trial of BPN14770 in the second quarter of this year for Fragile X Syndrome (FXS). Fragile X Syndrome is a genetic disorder that is the result of mutations in the FMR1 gene which is found on the bottom part of the X chromosome. Almost all cases are the result of mutations in the CGG triplet repeat, which is dramatically expanded (repeated) in the gene, almost like a genetic stutter. It was originally observed in chromosomal studies, where in certain culture conditions, the bottom part of one arm of the X chromosome was partially broken, hence, “fragile X.”
Males are affected more severely than females. There is developmental delay of speech and language by age two, and in males, typically mild to moderate intellectual problems, with about one-third of females intellectually disabled. Behavioral and emotional problems include anxiety and hyperactive behavior, attention deficit disorder, and attention problems. About a third of patients with Fragile X Syndrome have symptoms similar to autism spectrum disorders involving communication and social interaction. Seizures are also possible.
BPN14770 selectively inhibits phosphodiesterase-4D (PDE4D), which is involved in early and late stages of memory formation. Its mechanism of action may improve cognitive and memory function in Fragile X Syndrome, Alzheimer’s disease and other dementias, learning and developmental disabilities and schizophrenia. In preclinical trials, the compound has shown improved behavior in Fragile X Syndrome in mouse models and improved neuron connection quality.
In the trials in the fmr1 C57B16 knockout mice, a standard Fraxile X Syndrome animal models, the animals were treated for 14 days with the compound, which reduced hyperarousal, improved social behaviors, and caused increased natural behaviors such as nesting and marble burying, compared to the mice that received placebo. The benefits in the FXS mice lasted for two weeks after “drug washout.” Analysis of the neurons in the prefrontal cortex of the mice showed improvement in dendritic spine morphology.
In 147 human patients in three Phase I clinical trials, the safety profile was excellent and there were preliminary cognitive improvements in elderly patients. The company’s Phase II trials will be in adults with Fragile X Syndrome and in Alzheimer’s disease. It hopes to extend the trial to pediatric patients with Fragile X Syndrome later in 2018.
“We are very pleased to receive clearance from FDA to initiate our planned Phase II study of BPN14770 in adult males with Fragile X Syndrome,” said Mark Gurney, Tetra’s chairman and chief executive officer, in a statement. “This study will be carried out at Rush University Medical Center in Chicago, under the direction of principal investigator, Elizabeth Berry-Kravis, MD, PhD, one of the foremost experts on Fragile X Syndrome and founder of the university’s comprehensive Fragile X Clinic and Research Program, which provides care to more than 600 patients with Fragile X Syndrome.”
