During clinical trials, Independent Data Safety Monitoring Boards (DSMBs) sometimes assess trial safety, trial integrity, and how well the trials are upholding patient needs. According to Business Insider, the DSMB for biopharmaceutical company Anavex LifeSciences Corp. (“Anavex”)’s clinical trials recently evaluating the safety of three clinical trials evaluating ANAVEX 2-73 (blarcamesine) for patients with Rett syndrome. Altogether, the DSMB evaluated the Phase 2 AVATAR clinical trial, the Phase 2/3 EXCELLENCE trial, and the Phase 2 extension study. Ultimately, the DSMB recommended that all trials could continue without modification.
According to the National Center for Advancing Translational Sciences, this drug candidate is:
in Phase II trials for Alzheimer’s disease and Rett syndrome, phase I trials for epilepsy and in preclinical trials for multiple sclerosis and Parkinson’s disease. ANAVEX 2-73 is a sigma-1 receptor (SIGMAR1) agonist, which also has micromolar affinities for muscarinic M1–M4 receptors, the sodium channel site 2 and NMDAreceptors.
Prior studies suggest that activating or improving SIGMAR1 helps with neuroplasticity. In animal models of various conditions, ANAVEX 2-73 also helped to reduce seizures, protect memory, and act as an anti-depressant.
Thus far, the treatment has received Orphan Drug, Fast Track, and Rare Pediatric Disease designations.
Altogether, 33 adult patients with Rett syndrome enrolled in the Phase 2 AVATAR trial. During the trial, researchers evaluated the safety, efficacy, tolerability, and pharmacokinetics of liquid ANAVEX 2-73. The treatment was administered orally over a 7-week period. Next, 69 pediatric patients enrolled in the Phase 2/3 EXCELLENCE trial. The study was evaluating similar factors to the AVATAR trial, though over a twelve-week (4 month) period. Finally, 31 adult patients enrolled in the final Phase 2 trial, with similar goals. All those who finished the trials are eligible to continue on into future studies.
Over 900 MECP2 gene mutations cause Rett syndrome, a rare and severe neurological disorder. The mutations, which occur on the X chromosome, often occur spontaneously or by chance. 1 in every 10-15,000 live births globally has Rett syndrome. Altogether, the condition affects people of all racial and ethnic backgrounds. In terms of biological sex, Rett syndrome mostly impacts females. For males with Rett syndrome, the condition is often fatal around birth. In many cases, patients are unable to live independently. During the first 6-18 months following birth, patients often progress normally. However, language and motor skill regression then occurs. Symptoms and characteristics include:
- Social anxiety
- Loss of language skills
- Breathing issues (hyperventilation, breath-holding)
- Uncoordinated breathing
- Loss of motor skills, such as walking or crawling, and muscle tone
- Sleep disturbances
- Teeth grinding
- Difficulty chewing and swallowing
- Compulsive hand movements
- Heart rhythm abnormalities
- Gastrointestinal distress (acid reflux, constipation)
Learn more about Rett syndrome.