Positive Safety Data, Statistically Significant Improvements on Exploratory Clinical Endpoints
NEW YORK, NY, November 9, 2015
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL). On Saturday, investigators presented positive safety and cognitive efficacy data for ANAVEX 2-73, the Company’s lead investigational oral treatment for Alzheimer’s disease targeting sigma-1 and muscarinic receptors, which are believed to reduce protein misfolding including reduction of beta amyloid, tau protein and inflammation at the international CTAD 2015 conference in Barcelona, Spain.
Initial analysis of Phase 2a data demonstrated that the study met the primary objective of safety as ANAVEX 2-73 was well tolerated and results were consistent with prior Phase 1 clinical trial data. The secondary objectives were also met, with ANAVEX 2-73 showing cognitive improvement across all doses in all exploratory cognitive measurements, including the Cogstate battery, Mini Mental State Examination (MMSE), event-related potentials (ERP) and P300 tests, which consistently demonstrated improvements from baseline in the completed PART A portion of the study in 32 mild-to-moderate Alzheimer’s patients. Even though PART A was designed as a 5 week bioavailability trial that included a built-in wash-out period of 12 days and without an optimized dosing regimen, several Cogstate tests demonstrated highly statistically significant improvements. This finding was supported by a trend towards improvement in median MMSE score, which increased by +1.5 over baseline at week 5.
Positive effects on cognition were further supported by highly statistically significant biomarker effects of treatment at week 5 on one event-related potential (ERP) measure with a p-value of p<0.0007 and improvement in the P300 signal. The ERP biomarker scores improved compared to the initial data presented at AAIC in Washington, DC in July 2015, by which time not all patients had yet completed PART A.
All patients who completed PART A volunteered to continue in the longitudinal PART B extension study.
In the interim analysis of the first 14 patients at week 12, the PART B portion of the study demonstrated a positive trend towards improvement over 12 weeks of ANAVEX 2-73 treatment on the secondary functional outcome measure, the Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory (ADCS-ADL) by +3.21 points.
“While it is of prime importance to have confirmed that both the primary and secondary endpoints of the trial have been met, it is extremely encouraging to see the emergence of such strong cognitive signals after only 5 weeks of treatment. Such an outcome in a trial such as this is unprecedented in my experience, and the current results suggest that ANAVEX 2-73 could potentially make a significant difference in patients’ lives,” said Associate Professor Stephen Macfarlane, FRANZCP, Director of Aged Psychiatry at Alfred Health, who conducted the study. “We continue to receive extremely positive feedback about the effects of the drug from our study participants and their caregivers. The results justify a prospective comparison with current standard of care in a larger clinical trial.”
Professor Paul Maruff, Chief Scientific Officer of Cogstate commented: “The Cogstate tests measure people’s ability to store and use information. The results of the Phase 2a study demonstrate that ANAVEX 2-73 improves psychomotor function, attention and working memory. For attention and working memory these improvements were statistically significant with a p-value of p<0.05 and p<0.001, respectively and their magnitude clinically important. To my knowledge, we have not yet seen a drug that has improved quantitatively working memory to such an extent as seen with ANAVEX 2-73”.
Professor Harald Hampel, member of Anavex’s Scientific Advisory Board, and AXA Research Fund Chair at Sorbonne Universities’ Pierre and Marie Curie University (UPMC) in Paris, France, commented: “The collective data from this Phase 2a trial supports the concept of targeting the sigma-1 receptor with ANAVEX 2-73 with a degree of confidence that we did not foresee. Sigma-1 receptor presents an innovative interventional upstream approach to impact key cellular events believed to contribute to Alzheimer’s disease pathophysiology. The presented Phase 2a data underlines the importance of rigorously investigating a potential efficacy signal on co-primary outcomes such as cognition and function in larger and well-powered trials”.
“We are encouraged by the preliminary safety and efficacy data. We look forward to continuing with PART B of the Phase 2a trial and expect to provide data updates at 12 week, 26 week, 38 week and 52 week time points,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “While we remain focused on Alzheimer’s, the remarkably fast onset of clinical effect of ANAVEX 2-73 increases our options to potentially pursue additional indications for diseases characterized by working memory impairment and may enable clinical trials to be completed within shorter time frames.”
The presentation entitled “New Exploratory Alzheimer’s Drug ANAVEX 2-73: Assessment of Safety and Cognitive Performance in a Phase 2a Study in mild-to-moderate Alzheimer’s Patients” was presented by Professor Steve Macfarlane at CTAD in a late-breaking oral session and is available on the publications page of the Anavex website.
About the ANAVEX 2-73 Phase 2a Study
32 subjects who met NINCDS-ADRDA criteria for probable AD were recruited at five clinical sites in Melbourne, Australia. Subjects are between 55 and 85 years of age, and have a MMSE of 16 to 28. In PART A of the study, participants were administered ANAVEX 2-73 orally and IV in a randomized, open-label, 2-period, cross-over trial separated by a wash-out with adaptive study design lasting up to 36 days (5 weeks) for each participant. In PART B of the study, all participants are administered ANAVEX 2-73 daily orally.
At week 5 the MMSE score increased by +1.5 over baseline. The Cogstate Identification Task, Cogstate One Back Task and ERP Reaction Time all showed statistically significant improvements. In a preliminary interim readout of PART B data, ANAVEX 2-73 improved ADCS-ADL score, a functional measurement, over a period of 12 weeks by +3.21 over baseline, with 11 out of 14 (78.6%) patients improving. Both MMSE and ADCS-ADL are regulatory approved endpoints for pivotal Alzheimer’s disease trials.
The ongoing, multicenter Phase 2a adaptive trial of ANAVEX 2-73 in both male and female mild-to-moderate Alzheimer’s patients enrolled 32 participants. It commenced in January 2015 and the participants, the majority of whom are also taking donepezil, have now completed PART A of the two-part trial. Lasting up to 36 days (5 weeks) for each patient, PART A was a simple randomized, open-label, two-period trial with an on-off-on not-yet-optimized dosing regimen to assess bioavailability, and cross-over between oral (30mg/50mg) and IV (3mg/5mg) administration. Event-related potentials (ERP) were used to assess cognitive effects and optimize dosing of ANAVEX 2-73. PART B is an open-label extension for a further 52 weeks. Initially planned for 26 weeks, PART B was extended to 52 weeks as a result of requests from patients and caregivers. PART B utilizes daily oral dosing in order to establish a longer drug effect.
The primary endpoint of the Phase 2a trial is evaluation of safety and tolerability of ANAVEX 2-73, which had shown potential in preclinical studies to prevent, halt and/or reverse the course of the disease. Secondary endpoints were dose response, bioavailability, and exploratory cognitive effects using electroencephalographic (EEG) activity and event-related potentials (ERP), Cogstate battery, Mini Mental State Examination (MMSE), and evaluation of Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory (ADSC-ADL) as well as the exploration of ANAVEX 2-73 as a potential add-on therapy to donepezil, the current standard of care. The combination of ANAVEX 2-73 and donepezil (Aricept®) is known as ANAVEX PLUS.
Additional information regarding the trial is available from the U.S. National Institutes of Health (NIH) clinical trials database at www.clinicaltrials.gov.
About Alzheimer’s Disease
Today, Alzheimer’s disease remains the largest unmet medical need in neurology. More than 25 million people are currently diagnosed with Alzheimer’s, with the associated cost of care estimated to exceed $200 billion annually. By 2050, 100 million people are expected to be living with the disease. Alzheimer’s disease is a neurological disorder generally characterized by memory loss and cognitive decline. A neurodegenerative form of dementia, the disease begins with mild symptoms and becomes progressively worse.
The 8th Annual International Conference on Clinical Trials for Alzheimer’s Disease (CTAD) gather more than 800 global researchers to review the most important and promising developments in the field. Clinical trial teams from around the world report on their efforts to identify new biomarkers, discover more sensitive tools to identify those at risk for the disease and assess the effectiveness of new treatments.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel drug candidates to treat central nervous system (CNS) diseases and various types of cancer. Anavex’s lead drug candidates, ANAVEX 2-73 and ANAVEX PLUS, the combination of ANAVEX 2-73 and donepezil (Aricept®), are currently in a Phase 2a clinical trial for Alzheimer’s disease. The drug combination ANAVEX PLUS produced up to 80% greater reversal of memory loss in Alzheimer’s disease models versus when the drugs were used individually. ANAVEX 2-73 is an orally available drug candidate that targets sigma-1 and muscarinic receptors and successfully completed Phase 1 with a clean data profile. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s disease. It has also exhibited anticonvulsant, anti-amnesic, neuroprotective and anti-depressant properties in convulsive epileptic animal models, indicating its potential to treat additional CNS disorders, including epilepsy and others. Michael J. Fox Foundation (MJFF) for Parkinson’s Research has awarded Anavex a research grant to develop ANAVEX 2-73 for the treatment of Parkinson’s disease to fully fund a preclinical study, which could justify moving ANAVEX 2-73 into a Parkinson’s disease clinical trial. Further information is available at www.anavex.com.
Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks set forth in the Company’s most recent Annual Report on Form 10-K filed with the SEC. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.
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