Anavex's Phase 2b/3 Alzheimer's Data | Cancer Detection and Treatment Applications for Trump's $500B AI Investment
Lickety-Split Analytics
Good morning. The JPM healthcare week was in San Francisco last week. I was supposed to attend, but came down with a terrible bug just before. We were told the security was heightened this year and only two insurance companies were in attendance, one of which I had a meeting scheduled with. This week we wanted to focus on one of the data presentations that took place at JPM.
Anavex’s Phase 2b/3 AD Data and Comparison with Marketed Treatments
Anavex published results from the Phase 2b/3 trial in AD in The Journal of Prevention of Alzheimer’s Disease. The results were presented at JPM last Thursday morning, including a preview of the topline results from the open label extension (OLE) study.
There are currently only two disease modifying treatments for AD that are FDA or EMA approved and one additional treatment removed from the market due to the adverse side effect profile.
Lecanemab (Leqembi)
FDA approved for early AD July 2023
EMA approved for early AD Nov 2024
Donanemab (Kisunla)
FDA approved for early AD July 2024
Currently under EMA review, decision expected in Q1 2025
Aducanumab (Aduhelm)
FDA approved June 2021; Biogen removed from market in 2024
We gathered the data from Eli Lilly’s phase 3 TRAILBLAZER-ALZ 2 trial testing donanemab and Biogen’s phase 3 Clarity AD trial testing lecanemab to put the data from Anavex’s phase 2b/3 data testing blarcamesine in perspective.
Cognitive and Function Endpoints
ADAS-Cog13 and ADAS-Cog14
The ADAS-Cog13 assesses cognitive function by evaluating 13 domains with a total score ranging from 0 to 85. Domains include word recall, naming objects and figures, orientation, spoken language ability, and more. Higher scores indicate greater cognitive impairment. The ADAS-Cog14 assessment that Biogen used adds an additional domain, executive function, often measured through tasks like digital symbol substitution tests, and is measured on a 90 point scale.
Anavex achieved statistical significance in the ADAS-Cog13 co-primary endpoint reaching a 36.3% slowing of cognitive decline compared to placebo at 48 weeks. Participants with the common SIGMAR1 gene variant experienced an even greater significant benefit, slowing progression by 49.8% at week 48 on the ADAS-Cog13 endpoint. Eli Lilly’s drug reached a 35.3% slowing in their Low/Medium Tau subgroup and Biogen reached 25.8% slowing. It’s important to note, both competitors’ study lasted a year and a half compared to Anavex’s 11 month study.
Activities of Daily Living (ADCS-ADL)
Activities of Daily Living assesses functional ability based on activities found in daily life. Measures include the ability to eat, dress, bathe, toilet, groom, transfer, and walk. A higher score indicates better function.
Anavex didn’t meet statistical significance (p=0.35) on this co-primary endpoint. We believe this may be due to using the standard ADCS-ADL score, which may not be sensitive enough for early AD and better suited for Mild AD. Eli Lilly and Biogen for comparison used the ADCS-iADL and ADCS-MCI-ADL scales, which are fine tuned to catch decline from normal to early AD.
Current regulatory guidance from the FDA suggests that a sole cognitive endpoint is sufficient for demonstrating significance in early AD study populations
Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)
CDR-SB evaluates cognitive and functional abilities in six domains: memory, orientation, judgment & problem solving, community affairs, home & hobbies, and personal care. Each domain is scored from 0 to 3, with the total score ranging from 0 to 18. Higher scores indicate greater impairment
Anavex met statistical significance (p=0.010*) in this secondary endpoint, reaching a 27.6% slowing of disease progression. This resembles Biogen’s drug (27.1%) and Lilly’s combined data (28.9%), but falls behind Lilly’s Low/Medium Tau subgroup (36%).
Safety Data
We have included a couple of safety data comparison tables of which we will summarize the key takeaways.
Treatment Emergent Adverse Effects
Patients with ≥1 serious treatment-emergent adverse effects (TEAEs) occurred in 56 participants (16.7%) in the blarcamesine and 17 (10.1%) in the placebo group. Most of Anavex’s adverse effects were transient and mild to moderate in severity, including dizziness, confusion, and balance problems. Management believes these side effects could be curbed with nighttime administration, rather than early morning administration. There were no deaths attributable to blarcamesine or placebo, however, both donanemab and lecanemab trials saw deaths considered treatment related (lecanemab’s data doesn’t specify count).
ARIA Rates
ARIA refers to Amyloid-Related Imaging Abnormalities, changes seen in brain imaging.
ARIA-E refers to edema, swelling of fluid collection in the brain
ARIA-H refers to hemorrhages, AKA micro brain bleeds
Eli Lilly’s drug and Biogen’s drug both have significant ARIA rates, whereas, “Blarcamesine has a demonstrated safety profile and does not require routine MRI monitoring, and given its differentiated mechanism of action, could represent a novel treatment that is complementary or an alternative to the anti-beta amyloid drugs.”
Anavex’s blarcamesine could be a good alternative to anti-beta amyloid drugs, that have significant safety concern due to high ARIA rates.
Preview of Open-Label Extension Study Topline Data Released at JPM 2025
Long-term Treatment Benefits
Over three years of treatment with blarcamesine (ANAVEX®2-73) in the ATTENTION-AD trial, patients with early Alzheimer’s disease showed significantly reduced clinical decline, indicating continued clinical benefits. The trial extended from a 48-week double-blind phase to an open-label extension (OLE) for up to 144 weeks.
Safety Profile
The extended treatment period revealed no new safety concerns and maintained a good safety profile. There were no deaths linked to the drug, and adverse events were mostly mild to moderate, manageable with adjusted dosing schedules. The frequency of dizziness, the most common side effect, was notably reduced in the maintenance phase.
Efficacy Data
A delayed-start analysis model showed that early initiation of blarcamesine treatment led to better outcomes in cognitive function (ADAS-Cog13) and daily living activities (ADCS-ADL) compared to delayed treatment.
Significant differences were observed in ADAS-Cog13 at 144 (LS mean difference -2.70, P = 0.0348) and 192 weeks (LS mean difference -3.83, P = 0.0165). Mean difference between treatment groups showed that earlier treatment clinically improved progression by over 2 points (LS mean difference at Week 192 +4.30, P = 0.0206).
ADCS-ADL showed numerically favorable results for the early start group over the late start group at Week 144 (LS mean difference +2.32, P = 0.125). The treatment difference continued to increase up to Week 192 and reached statistical significance (LS mean difference +4.30, P = 0.0206).
Compassionate Use
74 participants continue to receive blarcamesine under compassionate use, with some treated for over 9 years without severe adverse events, reinforcing the drug's safety over long-term use.
Next Steps for blarcamesine in Early AD
Anavex received acceptance for the EMA filing in Dec 2024. The EMA reviews an application for 210 “active” days, which can take more time when the EMA requests further information. This gives an expected EMA approval decision sometime in late 2025. Given the recent EMA filing acceptance, it's reasonable to anticipate that Anavex might soon submit a BLA to the FDA for approval of blarcamesine in early AD. Additionally, long-term Open Label Extension data is expected to be presented at the AD/PD 2025 conference, April 1-5, 2025.
In Conclusion
Anavex has a cash runway of up to 4 years based on the last quarter’s burn. They have no debt and total cash of $138M. Their stock is trading for $9.85 per share currently with a market cap $781.15M. Assuming approval, we believe there is significant opportunity for Anavex, as long-term care for people with AD and other dementias are projected to reach $1 trillion by 2050 in the United States alone. AD makes up around 60-80% of all dementias, presenting the opportunity to relieve significant medical burden.
Trump’s $500B AI Investment Project: Applications in AI-Driven Cancer Detection and Treatment
Yesterday President Trump announced a $500 billion investment into an AI infrastructure project named “Stargate”. Key figures at the announcement were Larry Ellison, the co-founder and CEO of Oracle, alongside Sam Altman of OpenAI and Masayoshi Son from SoftBank. These leaders spoke to emphasize the project’s significance and potential applications.
Larry Ellison made a particularly intriguing statement (towards the end of the video). He discussed the possibility of developing personalized cancer vaccines based on data from early detection cancer blood tests. A simple blood test could identify the type and location of cancer, after which the DNA would be sequenced. Within 48 hours, an individualized cancer vaccine could be developed. Each step in this process would leverage AI to enhance health outcomes across the U.S.
This vision suggests a collaboration, where companies like Grail could handle the cancer detection tests, Illumina could take on DNA sequencing, and another entity would be responsible for developing the personalized “vaccine”. Makes a bit more sense why the FTC blocked the Grail-Illumina merger.
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