Achieved statistical significance on primary imaging-based endpoint, changes in markers of central pain processing, in 11 subjects
Observed corresponding trends of improvement on multiple secondary endpoints, including average daily pain scores and the Revised Fibromyalgia Impact Questionnaire (FIQR)
Data support further development of NYX-2925 in fibromyalgia
Improvement trends were also observed on multiple secondary endpoints, including patient-reported pain scores, as measured by the Numeric Pain Rating Scale (NPRS), and the Revised Fibromyalgia Impact Questionnaire (FIQR). NYX-2925 was well tolerated with no subjects reporting treatment-related serious adverse events. Based on these positive interim data,
“NYX-2925 shows significant and promising effects in patients with fibromyalgia,” said
“In our first data on NYX-2925 in patients, we are very pleased to see robust effects on the objective biomarkers and trends toward improvement on the patient-reported outcomes,” said
The study is ongoing with the full data expected to read out in the first half of 2019. Once completed, the company plans to submit the detailed results from this study for publication and presentation at future scientific and medical meetings.
This study is being conducted in women diagnosed with fibromyalgia. Over the course of the study, subjects undergo a series of functional magnetic resonance imaging (fMRI) scans, combined with proton magnetic resonance spectroscopy (H-MRS), to measure key brain activity markers known to be associated with central sensitization of pain. The study’s primary endpoint is the evaluation of changes in these specific markers. Secondary endpoints include several patient-reported assessments to evaluate the effects of NYX-2925 on clinical outcomes. These patient-reported outcomes include average daily pain and worst daily pain measured using the NPRS, the impact of their fibromyalgia on daily living measured by the FIQR, mood and anxiety measured by the Hospital Anxiety and Depression Scale (HADS), and cognitive impairment measured using the Multidimensional Inventory of Subjective Cognitive Impairment (MISCI).
At baseline, the subjects included in the interim analysis had a mean average daily pain score of 5.8 on the numeric pain rating scale, which has a range from 0 to 10 (where 0 = no pain and 10 = worst pain imaginable) and had a mean baseline total FIQR score of 51 (this scale has a maximum score of 90 with higher scores indicating worse fibromyalgia). Based on these scores, these subjects are considered to have moderate-to-severe fibromyalgia.
Primary Endpoint Findings – fMRI/H-MRS
The interim analysis of imaging measures showed that NYX-2925 reduced Glx levels in brain regions known to be involved in central pain processing. Fibromyalgia is associated with increased overall levels of Glx and prior studies have shown a correlation between pain severity and higher Glx levels in certain brain regions. Compared to placebo, administration of NYX-2925 resulted in statistically significant reductions of Glx levels in these brain regions, including a reduction in resting Glx levels in the dorsal anterior cingulate cortex (p=0.02) and a reduction of Glx increase in the posterior insular cortex following an evoked pain stimulus (p=0.01). NYX-2925 administration also resulted in connectivity changes that have previously been shown to be associated with central pain processing and alleviation of fibromyalgia symptoms, including reduced connectivity between the posterior insular and the default mode network. The observed changes in objectively measured Glx levels and connectivity correlated with improvements on patient-reported outcomes.
Secondary Endpoint Findings – Patient-Reported Outcomes
The interim analysis also showed trends of clinical improvement in key symptoms of fibromyalgia following treatment with NYX-2925.
About the Exploratory Study
This study is a single-blind, exploratory, placebo-controlled, pilot study to assess the efficacy and safety of daily oral NYX-2925 in fibromyalgia subjects (NCT03249103). Subjects are assessed in the week leading up to treatment to establish baseline values for imaging endpoints and patient-reported endpoints, then receive daily oral doses of 20 mg of NYX-2925, 200 mg of NYX-2925, and placebo for two weeks each. Following the last week of treatment, subjects are evaluated during a one-week follow-up period. During each of the two-week treatment periods, participants undergo fMRI scans and H-MRS to evaluate Glx levels and connectivity patterns in pre-specified brain regions known to be particularly involved in central pain processing. Data analysis was performed by analysts that were blinded to treatment sequence. Over the course of treatment, subjects are also assessed across a range of symptoms with patient-reported outcomes using the NPRS, FIQR, MISCI, and HADS. Safety and tolerability are also monitored over the course of the study.
NYX-2925 is a novel NMDA receptor modulator currently in Phase 2 clinical development for the treatment of painful diabetic peripheral neuropathy (DPN) and under evaluation in an exploratory Phase 2 study in fibromyalgia. NYX-2925 has demonstrated robust activity in preclinical models of numerous neuropathic pain conditions with a favorable tolerability profile. In a Phase 1 clinical study in healthy human subjects, NYX-2925 was well tolerated across a wide dose range, including dose levels well in excess of the expected therapeutic levels.
Aptinyx Inc. is a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of proprietary synthetic small molecules for the treatment of brain and nervous system disorders. Aptinyx has a platform for discovery of novel compounds that work through a unique mechanism to modulate – rather than block or over-activate – NMDA receptors and enhance synaptic plasticity, the foundation of neural cell communication. The company has three product candidates in clinical development in central nervous system indications, including chronic pain, post-traumatic stress disorder, and cognitive impairment associated with Parkinson’s disease. Aptinyx is also advancing additional compounds from its proprietary discovery platform, which continues to generate a rich and diverse pipeline of small-molecule NMDA receptor modulators with the potential to treat an array of neurologic disorders. For more information, visit www.aptinyx.com.
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the company’s business plans and objectives, therapeutic effects of the company’s product candidates, expectations regarding the design, implementation, enrollment, timing, and success of its current and planned clinical trials, expectations regarding its preclinical development activities, and expectations regarding its uses of capital. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of the company’s product candidate development activities and planned clinical trials; the company’s ability to execute on its strategy; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in
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Source: Aptinyx Inc.