Oral SBMA therapy shows safety and tolerability in Phase 1 trial
NIDO-361, Nido Biosciences’ experimental oral treatment for spinal and bulbar muscular atrophy (SBMA), was seen to be generally safe and well tolerated in healthy adults who participated in an initial clinical trial.
Results of the Phase 1 study (ACTRN12622000964718) were presented during the 2023 International Kennedy’s Disease Patient Conference held in London on Nov. 4–5.
Nido also presented preliminary findings in an ongoing and observational study in SBMA patients, which appear to support muscle magnetic resonance imaging (MRI) use in evaluating treatment efficacy in clinical trials and as a measure of disease progression.
The presentation, “Nido-361 for the Treatment of SBMA: Updates on Clinical Development Program,” included data from both studies and was published by The Cochrane Library.
Targeting 2 specific proteins shows promise for SBMA in early models
Phase 2 study being planned for people with spinal and bulbar muscular atrophy
A Phase 2 trial is planned and expected to open next year.
“The Phase 1 study results and interim analyses of our ongoing observational study support the further advancement of our clinical program,” said Vissia Viglietta, MD, PhD, Nido Biosciences’s chief medical officer, said in a press release.
Study findings aided in “the selection of active and safe doses and confirming muscle MRI as a reliable primary endpoint [trial goal] for our upcoming Phase 2 trial, which we anticipate will begin enrollment in [the first quarter of] 2024,” Viglietta added.
SBMA, also known as Kennedy’s disease, is a rare form of spinal muscular atrophy (SMA) that almost exclusively affects men. The disease is caused by mutations in the androgen receptor (AR) gene, located on the X chromosome, which provides instructions for making the androgen receptor protein.
Mutations result in the abnormal repetition of a section of DNA in the gene, leading to an abnormally elongated version of the protein that affects its ability to function. But how defective androgen receptor proteins affects motor neurons — the specialized nerve cells that control muscle movement — still is not clear.
It is thought, however, that the abnormal protein accumulates at toxic levels inside cells, damaging them.
Disease symptoms usually begin in adulthood, and they include progressive weakness and atrophy of muscles closer to the trunk and those of the mouth and throat.
NIDO-361 is a small molecule that binds to a distinct and novel site on the androgen receptor, correcting problems with the AR protein and restoring health to cells.
Reasonable safety with oral NIDO-361 seen at ascending daily doses
The two-part Phase 1 trial evaluated the safety, tolerability, and pharmacological properties of oral NIDO-361, delivered in single and multiple escalating doses, against a placebo capsule. It enrolled 64 healthy men, ages 18 to 55, at a site in Australia.
In its first part, single ascending doses of NIDO-361, reported to range from 75 to 500 mg, or a placebo were given to 40 adults, assigned to one of five, eight-person groups. They then underwent two days of monitoring for treatment safety, tolerability, and pharmacokinetics — how the body absorbs, distributes, metabolizes, and excretes compounds over time — with follow-up assessments one week later.
In its second part, multiple ascending NIDO-361 doses, or a placebo, were given daily for seven days to 24 men placed across three groups. Doses administered here were determined based on earlier safety and tolerability findings, and similar safety and tolerability assessments followed.
Results presented at the conference supported NIDO-361’s safety and tolerability in single and multiple daily oral doses, with no serious adverse events reported.
The two-year observational study is evaluating the relationship between muscle MRI data and clinical outcomes. Preliminary data at six and 12 months after patient enrollment indicated that muscle MRIs could be a reliable measure of outcomes, and of use in future clinical trials of NIDO-361 in determining treatment effectiveness.
Previous research also supports changes seen on muscle MRIs as a way of measuring response to therapy in trials of people with neuromuscular diseases, and as a potential marker of disease progression.
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