Anavex Life Sciences Corp (AVXL)

[georgejjl]

Dare to compare Anavex 2-73 to trofinetide. I dare you!!!

Anavex 2-73 is as lease twice as effective as trofinetide

www.neurenpharma.com/irm/PDF/1857_0/PublicationinNeurologyDoubleblindrandomizedplacebocontrolledstudyoftrofinetideinpediatricRettsyndrome

Among the 3 outcome measures with p < 0.05, the magnitude
of effect (% change of the median score) for RTT-DSC was 15%
(vs 5% for placebo) and the magnitude of effect (% change of the
mean score) for RSBQ was 16% (vs 6% for placebo). For CGI-I,
the mean was 3.0 for the 200 mg/kg bid group and was 3.5 for
placebo, with more than 20% of participants scoring a 2, “much
improved,” compared with less than 5% of those on placebo.
Cohen d effect sizes were -0.645 for CGI-I, -0.247 for the RTTDSC, and -0.487 for the RSBQ total

...Safety
Safety and tolerability of trofinetide was very good at all 3 dose
levels. No deaths occurred in the study. Only one participant
(200 mg/kg bid group) was withdrawn from the study at the
request of her parents because of increased mild gastroesophageal reflux, moderate diarrhea, and mild vomiting,
which resolved uneventfully after discontinuation. Four SAEs
occurred in 3 participants: 1 participant receiving placebo, 1
participant receiving 100 mg/kg bid, and 1 participant receiving 200 mg/kg bid. All the SAEs were deemed not related
to study medication and resolved by the end of the study.
A summary of AEs during the double-blind treatment period
occurring in at least 2 participants is shown in table 2. The
most common AEs reported during the double-blind period
across all treatment groups were diarrhea (27%), vomiting
(15%), upper respiratory tract infection (12%), and pyrexia
(10%). Diarrhea was reported in 27% in the 50 mg/kg bid group,
13% for the 100 mg/kg bid group, and 56% in the 200 mg/kg bid
group. Most AEs were mild or moderate in intensity and most
events were considered not related to study drug.
No systematic evidence of withdrawal effects was observed
when the study drug was discontinued. Clinical laboratory
tests, ECGs, vital signs, and physical examinations (including
funduscopy and tonsil size) indicated no time- or dosedependent patterns.


https://www.anavex.com/anavex-life-sciences-announces-preliminary-clinical-efficacy-data-of-its-u-s-phase-2-clinical-trial-of-anavex2-73-in-patients-with-rett-syndrome/

Preliminary Clinical Data is derived from the ANAVEX®2-73-RS-001 study on the first 6-patient cohort ranging in age from 18 to 36 years, who completed the pharmacokinetic (PK) part of the study and who received a low dose of approx. 5 mg daily oral liquid dose of ANAVEX®2-73 (blarcamesine) for 7 weeks. Patients are continuing participation in the ANAVEX®2-73-RS-001 open label extension study.

Both efficacy endpoints, the Rett Syndrome Behaviour Questionnaire (RSBQ) and the Clinical Global Impression – Improvement (CGI-I) showed significant improvement with respect to baseline after 7 weeks of treatment. The RSBQ Total average scores improved from 50 to 34 points (2-tailed Wilcoxon signed rank test, p = 0.027) and the CGI-I scores were positively correlated with RSBQ Total scores at 7 weeks (2-tailed Spearman’s rho = 0.956, p = 0.003).

Supporting the clinical assessments, plasma levels of the biomarker Glutamate also decreased significantly (Week 0 vs. Week 7; 2-tailed Wilcoxon signed rank test, p = 0.046) and levels of Glutamate at Week 7 were directly correlated with CGI-I scores at Week 7 (2-tailed Spearman’s rho = 0.837, p = 0.038) with greater decreases in Glutamate associated with greater improvement in these efficacy scores.

Glutamate is the main excitatory neurotransmitter in the brain and is known to be higher in patients with Rett syndrome compared to healthy subjects in the brain, as measured by magnetic resonance imaging spectroscopy (MRS), as well as in cerebrospinal fluid (CSF) and blood plasma.

Additionally, the magnitude of GABA change was inversely correlated with the magnitude of decrease in RSBQ Total scores (2-tailed Spearman’s rho = -0.812, p = 0.050) and GABA changes demonstrated an inverse correlation of the magnitude of Glutamate changes (2-tailed Spearman’s rho = -0.829, p = 0.042).

GABA is the main inhibitory neurotransmitter in the brain, known to be deficient in animal models of Rett syndrome. Excitatory-inhibitory imbalances postulated in many neurologic disorders, including Rett syndrome, have been linked to imbalances between Glutamate and GABA[1],[2].

An independent DSMB review determined that ANAVEX®2-73 (blarcamesine) was well tolerated, with no SAEs reported and with all patients completing the study. Therefore, the DSMB issued a positive recommendation for the continuation of the Phase 2 Rett syndrome study without any modifications.

“This is a remarkable first strong signal for patients with Rett syndrome especially given that the strong effects were seen in adult patients, and we look forward to discussing these results with the FDA and the European regulatory agency as we continue our Rett Syndrome Program including pediatric patients,” said Walter E Kaufmann, MD, Principal Investigator of the study and Chief Medical Officer of Anavex. “Importantly, we’ve now observed that the ANAVEX®2-73 (blarcamesine) effect is correlated with changes of Glutamate and GABA levels, objective measures and biomarkers in several neurodevelopmental disorders.”

Detailed results will be presented at the 6th European Rett Syndrome Conference in Tampere, Finland, September 27-28, 2019 and submitted for publication in a peer-reviewed journal.

Neurobehavioral effects of ANAVEX®2-73 (blarcamesine) previously observed in preclinical studies were also detected in patients with Rett syndrome, pointing to the ability of translation of preclinical to clinical data. ANAVEX®2-73 (blarcamesine) has received orphan drug designation from the FDA and EMA for the treatment of Rett syndrome.

Christopher U Missling, PhD, President and Chief Executive Officer of Anavex stated, “We are encouraged by the insights gleaned from these first clinical data for ANAVEX®2-73 (blarcamesine) in patients with Rett syndrome and we look forward to both confirm this clinical data and continue the Rett syndrome program with determination. In addition to Rett syndrome[3], Anavex has ongoing clinical development programs for ANAVEX®2-73 (blarcamesine) for the treatment of Alzheimer’s disease[4] and Parkinson’s disease dementia[5].”

Good luck and GOD bless,