NYX-2925 Lowers Marker of Pain Severity in Fibromyalgia Patients, Early Phase 2 Trial Results Show

NYX-2925 Lowers Marker of Pain Severity in Fibromyalgia Patients, Early Phase 2 Trial Results Show

The chronic pain treatment candidate NYX-2925 lowered levels of a brain activity marker called glutamine (Glx), associated with pain severity, according to preliminary results of a Phase 2 pilot trial in patients with moderate to severe fibromyalgia.

The findings also showed improvement in patient-reported pain, as well as a reduction in fibromyalgia’s impact on daily living, and less anxiety, depression, and cognitive impairment.

Aptinyx’s NYX-2925 is a modulator of N-methyl-D-aspartate (NMDA) receptors, key in excitatory nerve transmission mediated by the neurotransmitter glutamate and are dysfunctional in several nervous system disorders. When pain becomes chronic, it is largely mediated by central learning and memory processes.

The investigational compound increases neural cell communication, which Aptynx believes is uniquely suited to treat chronic pain. A Phase 1 study (NCT02834741) in healthy subjects showed that NYX-2925 was well-tolerated across a wide dose range.

The exploratory phase 2 study (NCT03249103) is evaluating the efficacy and safety of daily oral treatment with 20 mg and 200 mg of NYX-2925 as well as a placebo over six weeks.

During the study, patients have functional magnetic resonance imaging scans combined with an approach called proton magnetic resonance spectroscopy to assess brain activity markers (primary outcome) associated with central sensitization of pain, which is key in chronic pain.

Secondary outcomes include average daily pain and worst daily pain assessed with the Numeric Pain Rating Scale (NPRS), fibromyalgia’s impact on daily living measured by the revised Fibromyalgia Impact Questionnaire (FIQR), anxiety and mood with the Hospital Anxiety and Depression Scale (HADS), and cognitive impairment with the Multidimensional Inventory of Subjective Cognitive Impairment (MISCI).

Safety and tolerability are also monitored. A one-week follow-up follows the last week of treatment.

The early analysis was conducted on the first 11 patients to have completed the study. At baseline, they had a mean average daily pain score of 5.8 and a mean total FIQR score of 51, indicating that they had moderate to severe fibromyalgia.

The results showed that, compared to a placebo, NYX-2925 was associated with statistically significant changes in levels of Glx — an amino acid related to glutamate — in brain regions with known involvement in pain. Prior research linked pain severity with increased levels of Glx. The team found that NYX-2925 decreased Glx in the dorsal anterior cingulate cortex and lessened the Glx increase in the posterior insular cortex following a pain stimulus. These brain regions have been associated with pain processing.

Treatment with NYX-2925 also decreased patient-reported pain scores, fibromyalgia’s impact, anxiety and depression occurrence, and cognitive impairment.

The data further showed that NYX-2925 administration resulted in less connectivity between brain networks previously associated with central pain processing and alleviation of fibromyalgia symptoms. NYX-2925 was well-tolerated, with no patients reporting serious adverse events.

“NYX-2925 shows significant and promising effects in patients with fibromyalgia,” Daniel Clauw, MD, an investigator in the study and a professor at the University of Michigan, said in a press release. Clauw noted that although the number of patients for this early analysis was limited, NYX-2925 was associated with “strong and significant impacts on imaging markers known to be associated with central processing in chronic pain.”

The investigator further said that these results are superior to those of a post-approval study on Lyrica (pregabalin, by Pfizer). “We believe these findings indicate that NYX-2925 affects pain processing within the brain,” Clauw said.

Norbert Riedel, PhD, Aptinyx’s president and CEO, said: “We are very pleased to see robust effects on the objective biomarkers and trends toward improvement on the patient-reported outcomes.” Riedel also said the findings show that NYX-2925 induces changes in key brain areas “that are known to translate into symptomatic relief for patients suffering from fibromyalgia.”

“These data enhance our confidence in the utility of NYX-2925 in chronic pain conditions and encourage us to advance it in development for the treatment of fibromyalgia,” Riedel said.

Full results are expected in the first half of 2019. Aptinyx plans to submit them for publication and present the data at scientific and medical meetings. Based on the positive preliminary data, the company expects to start a larger fibromyalgia Phase 2 trial in 2019.

In December 2017, Aptynix announced the completion of a $70 million series B financing round to fund the expansion of its pipeline of therapies, including NYX-2925.

Besides fibromyalgia, Aptynix is also conducting a Phase 2 trial of NYX-2925 in patients with painful diabetic peripheral neuropathy (NCT03219320). Patient enrollment is ongoing — find more information here.