​​Anavex Life Sciences Therapeutic Showed Benefit in Patients with Parkinson’s Disease

Anavex Life Sciences recently reported that its preliminary 48-week Parkinson’s disease dementia Phase 2 extension study demonstrated that oral once daily Anavex 2-73 (blarcamesine) had longitudinal beneficial effects for patients. Those benefits included improved scores on tests used to determine motor impairment and cognition.

Anavex is a publicly traded, clinical-stage biopharmaceutical company that develops differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders. These disorders include Alzheimer’s disease, Parkinson’s disease, and other central nervous system disorders.

Anavex 2-73 is an orally-available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Parkinson’s disease is a chronic, debilitating central nervous system disease, and the second largest neurodegenerative disorder after Alzheimer’s disease. Parkinson’s is characterized by well-known motor symptoms including tremors, stiffness of limbs, slowness of movements, and difficulties with posture and balance, as well as by nonmotor symptoms.

About 1 million people in the United States and more than 10 million people worldwide live with this Parkinson’s, which is more common in people over 60. Its prevalence is expected to increase significantly as the average age of the population increases.

“[Parkinson’s disease dementia] is a debilitating disorder with significant comorbidities and there has not been a mechanistically novel medication approved for PDD in over 20 years,” Jaime Kulisevsky, M.D., Ph.D., principal investigator of the initial Phase 2 study, said at the AD/PD International Conference. “Hence, new therapies are urgently needed to alleviate this suffering and disability.”

Efficacy and Safety

The Phase 2 study demonstrated for the first time that clinical symptoms consistently improved during the study for patients under active oral once daily Anavex 2-73 treatment.

The study assessed the safety, tolerability and efficacy of blarcamesine. Among the tests used to measure the drug’s impact included the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) that assesses motor skills; the REM Sleep Behavior Disorder Screening Questionnaire; the Clinical Global Impression-Improvement (CGI-I) and the Montreal Cognitive Assessment.

Preliminary analysis revealed that Anavex 2-73 was found generally safe and well tolerated by patients. The safety findings in this study are consistent with the known safety profile of Anavex 2-73. With regard to efficacy, patients performed better while on Anavex 2-73.

The extension study was offered to participants after completion of the initial double-blind, placebo-controlled Phase 2 study. Study participants were allowed to stay on a stable regimen of anti-Parkinson’s disease medications (e.g., levodopa, dopamine agonists, MAO-B inhibitors, entacapone).

In the initial Phase 2 study, Anavex 2-73 treatment demonstrated statistically significant improvements compared to placebo (intention-to-treat population) for MDS-UPDRS Total score. From baseline to the end of the 14-week trial, the MDS-UPDRS Total score improved by minus 10.98 points in the Anavex 2-73 high dose group and worsened by 3.53 points in the placebo group. This corresponds to a relative improvement of 18.9% over 14 weeks. This data was also consistent with expression levels of pathological dysregulated neurodegenerative genes, including Parkinson’s disease genes, which were significantly restored by the therapeutic effect of Anavex 2-73.

The Pandemic … and Progress

Due to the COVID-19 pandemic, the start of the extension phase was delayed by approximately 41 weeks at the end of the initial study, leading to a reduced enrollment rate for the extension phase. The period between the end of the first phase and start of the extension phase is known as a “drug holiday.” This period provided an opportunity to compare clinical scores between periods without Anavex 2-73 treatment and treatment with the drug during the extension phase.

All efficacy endpoints worsened during the drug holiday. However, data showed consistent improvement during the extension phase when patients resumed Anavex 2-73 treatment. This was consistent with the pattern observed for all efficacy measures in the extension phase.

The two endpoints measured in this study — MDS-UPDRS Part II and III, and CGI-I — are potential primary and key secondary endpoints in Anavex’s next planned Parkinson’s disease study.

Recognition and Company Response

The Michael J. Fox Foundation awarded Anavex a research grant for an imaging-focused Parkinson’s disease clinical trial with Anavex 2-73. The foundation previously awarded Anavex a research grant, which fully funded a preclinical study that established Anavex 2-73 as a potentially disease-modifying treatment for Parkinson’s disease.

At the request of the participants completing the 48-week open-label extension study, patient-requested treatment with Anavex 2-73 is continuing beyond the open-label 48 weeks through the compassionate use Special Access Scheme. Currently, participants in the compassionate use program for oral once daily Anavex 2-73 have been participating, on average, for over two years and counting.

“It is encouraging that the patients’ clinical symptoms consistently improved longitudinally over time during the extension phase under active Anavex 2-73 treatment,” said Christopher Missling, Ph.D., the president and CEO of Anavex. “This data suggests Anavex 2-73’s potential capability to slow and potentially reverse the life-altering symptoms of Parkinson’s disease, an urgent unmet global need.”