Information that was not included in the Press Release from the P2b/3 announcement.
As you know, I've been a strong proponent of filing our NDA with the EMA first. It is my belief that the EMA actually needs our drug because of the ease of distribution and safety profile. The FDA, on the other hand, has some requirements that may reduce our chances of an NDA approval. i.e. the need for multiple ethnic groups within the study is probably the biggest impediment.
Anyway, after reading the Press Release below it is my belief that Anavex has finally spoken with the FDA and was (verbally) turned down from submitting the P2b/3 study. I came to this conclusion because of the wording in the Press Release. See the sentence that I underlined in bold below.
This does NOT mean that Anavex will not receive approval from the FDA. It simply means that they are going to submit the NDA with the EMA first. Once approved with the EMA, they will get fast-tracked for approval with the FDA. This is my opinion, of course.
NEW YORK – July 28, 2024
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today presented comprehensive results from the Phase IIb/III study showing that blarcamesine (ANAVEX®2-73), once daily orally, significantly slowed clinical decline in people with early Alzheimer's disease (AD). The data were presented by Marwan Noel Sabbagh, MD, Professor of Neurology at Barrow Neurological Institute and Chairman of the Scientific Advisory Board at the 2024 Alzheimer's Association International Conference (AAIC).
Blarcamesine significantly slowed clinical progression by 38.5% and 34.6% at 48 weeks in 50 mg and 30 mg groups vs. placebo, respectively, on the prespecified primary cognitive endpoint ADAS-Cog13. As specified in the March 2024 FDA Guidance for Early AD, a sole cognitive measure can serve as the primary endpoint for early Alzheimer’s trials.[1] The protocol was designed with ADAS-Cog13 and ADCS-ADL as co-primary endpoints. The functional co-primary endpoint, ADCS-ADL, was trending positive but did not reach significance at Week 48. A possible explanation is that the ADCS-ADL scale is designed for AD with overt dementia and is less sensitive for early AD.[2] The prespecified key secondary composite endpoint CDR-SB, also recommended as an alternative primary endpoint for early AD in the new FDA guidance, is significant at both 30 mg and 50 mg at Week 48. The findings are supported by biomarkers from the A/T/N spectrum, including plasma Aß42/40-ratio and reduction of brain atrophy. Blarcamesine significantly slowed brain atrophy in key regions of interest, including the whole brain by 37.6%, total grey matter by 63.5%, and lateral ventricles by 25.1%.
“These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration,” said Dr. Sabbagh. “The advantage of blarcamesine is that it is a small oral molecule that exerts clinical benefits on cognition and neurodegeneration and could be appealing because of its route of administration and good comparative safety profile. The neuroimaging evaluation performed in the Phase IIb/III study demonstrated no neurological tissue damage such as hemorrhage or Amyloid-related imaging abnormalities (ARIA), as documented with other anti-amyloid targeted therapies. We believe the scalable and convenient features of blarcamesine could reduce crucial barriers within the currently complex healthcare ecosystem for Alzheimer's disease and provide broader access to a diverse population with early Alzheimer's disease.”
Blarcamesine, a small molecule administered orally once daily, demonstrated numerically superior clinical efficacy to approved therapies while also slowing neurodegeneration in early AD patients. Blarcamesine’s safety profile indicates not requiring routine MRI monitoring, and given its differentiated mechanism of action, could represent a novel treatment that could be complementary to the currently approved anti-beta amyloid monoclonal antibody drugs.
Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex commented: “Anavex's precision medicine approach, tailored to improving autophagy, a key clearance mechanism that removes protein aggregates and misfolded proteins across the Alzheimer's disease continuum and uniquely positions the Company to develop innovative solutions for patients and their families.” He continued: “People living with early Alzheimer's disease have the desire to maintain their sense of self for as long as possible. The study results provide the potential for people with more time to engage in meaningful activities. Full regulatory submission of blarcamesine in Europe (EMA) is expected in Q4 2024.” [No mention of filing with the FDA?!]
For the primary endpoint ADAS-Cog13, blarcamesine is significantly better than placebo for both 50 mg (-2.149; P = 0.021) at 48 weeks and for 30 mg blarcamesine dosage groups (-1.934; P = 0.026) at 48 weeks. The key secondary endpoint CDR-SB was significantly improved vs. placebo in both 50 mg (-0.465; P = 0.045) and 30 mg (-0.502; P = 0.020) assigned dose groups. CGI-I was significantly improved in both 50 mg (-0.314; P = 0.008) and 30 mg (-0.248; P = 0.024) groups.
In the respective safety population, common treatment-emergent adverse events included dizziness, which was transient and mostly mild to moderate in severity, and occurred in 120 participants (35.8%) during titration and in 76 participants (25.2%) during maintenance with blarcamesine and 10 (6.0%) during titration and 9 (5.6%) during maintenance with placebo. These events are manageable by adjusting titration schedule to slower titration and nighttime dosing, as has been positively observed in the blarcamesine compassionate use program.
“Alzheimer’s disease is such a devastating disease that affects tens of millions worldwide. The findings from this and previous studies with blarcamesine in Alzheimer’s disease further strengthen our belief in the potential of addressing the complex pathology in Alzheimer’s disease through an upstream precision medicine compensatory process, autophagy through SIGMAR1 activation,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “We like to thank all the people involved in the study for their invaluable contributions and we look forward to continuing our journey to address the high unmet need for Alzheimer’s disease patients with a potential new convenient orally available treatment option for Alzheimer’s disease.”
The presentation is available on the Investors section of the Company’s website at www.anavex.com.
Data from the blarcamesine Phase IIb/III ANAVEX®2-73-AD-004 trial to be published in an upcoming peer-reviewed journal.
This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval.
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