Alector Presents Baseline Characteristics for INVOKE-2 Phase 2 Clinical Trial of AL002 at the Alzheimer's Association International Conference® 2024 (AAIC®)
Alector presented baseline characteristics for the INVOKE-2 Phase 2 clinical trial of AL002, a TREM2 agonist, at AAIC® 2024. The trial, involving 381 participants with early Alzheimer's disease (AD), is the first global Phase 2 study evaluating a TREM2 agonist's safety and efficacy in slowing AD progression. Key points:
- Median age: 71 years (range: 51-85)
- 78% of participants ≥65 years old
- 50% female, 94% Caucasian
- 67% with mild cognitive impairment, 33% with mild dementia
- 59% heterozygous APOE e4 carriers
- All participants confirmed amyloid-positive
Results are expected in Q4 2024, with a long-term extension study ongoing. The baseline data confirm a representative study population for testing AL002's effects in early AD.
Alector ha presentato le caratteristiche di base per lo studio clinico di Fase 2 INVOKE-2 di AL002, un agonista del TREM2, all'AAIC® 2024. Lo studio, che coinvolge 381 partecipanti con una forma precoce di malattia di Alzheimer (AD), è il primo studio globale di Fase 2 che valuta la sicurezza e l'efficacia di un agonista del TREM2 nel rallentare la progressione dell'AD. Punti chiave:
- Età mediana: 71 anni (range: 51-85)
- Il 78% dei partecipanti ha ≥65 anni
- 50% femmine, 94% Caucasici
- 67% con lieve compromissione cognitiva, 33% con lieve demenza
- 59% portatori eterozigoti del gene APOE e4
- Tutti i partecipanti hanno confermato la positività all'amiloide
I risultati sono attesi nel Q4 2024, con uno studio di estensione a lungo termine in corso. I dati di base confermano una popolazione di studio rappresentativa per testare gli effetti di AL002 nella fase precoce dell'AD.
Alector presentó las características basales del ensayo clínico de Fase 2 INVOKE-2 de AL002, un agonista del TREM2, en AAIC® 2024. El ensayo, que involucra a 381 participantes con la enfermedad de Alzheimer (EA) en sus primeras etapas, es el primer estudio global de Fase 2 que evalúa la seguridad y eficacia de un agonista del TREM2 para ralentizar la progresión de la EA. Puntos clave:
- Edad media: 71 años (rango: 51-85)
- 78% de los participantes ≥65 años
- 50% mujeres, 94% caucásicos
- 67% con deterioro cognitivo leve, 33% con demencia leve
- 59% portadores heterocigotos de APOE e4
- Todos los participantes confirmaron ser positivos para amiloide
Se esperan resultados en el Q4 de 2024, con un estudio de extensión a largo plazo en curso. Los datos de base confirman una población de estudio representativa para evaluar los efectos de AL002 en la EA temprana.
Alector는 AAIC® 2024에서 AL002, TREM2 작용제에 대한 INVOKE-2 2상 임상 시험의 기초 특성을 발표했습니다. 이 시험은 조기 알츠하이머병 (AD) 환자 381명을 대상으로 하며, TREM2 작용제의 안전성 및 AD 진행 속도 저하에 대한 효과를 평가하는 최초의 글로벌 2상 연구입니다. 주요 사항:
- 평균 연령: 71세(범위: 51-85)
- 참가자의 78%가 65세 이상
- 50% 여성, 94% 백인
- 67%가 경증 인지 장애, 33%가 경증 치매
- 59%는 이형접합 APOE e4 보유자
- 모든 참가자가 아밀로이드 양성으로 확인됨
결과는 2024년 4분기에 예상되며, 장기 확장 연구가 진행 중입니다. 기초 데이터는 AL002의 조기 AD에 미치는 영향을 테스트하기 위한 대표적인 연구 집단을 확인합니다.
Alector a présenté les caractéristiques de base de l'essai clinique de Phase 2 INVOKE-2 sur AL002, un agoniste du TREM2, lors de l'AAIC® 2024. L'essai, qui implique 381 participants atteints de la maladie d'Alzheimer (MA) à un stade précoce, est la première étude mondiale de Phase 2 évaluant la sécurité et l'efficacité d'un agoniste du TREM2 pour ralentir la progression de la MA. Points clés :
- Âge médian : 71 ans (plage : 51-85)
- 78 % des participants ont ≥ 65 ans
- 50 % de femmes, 94 % de Caucasiens
- 67 % avec des troubles cognitifs légers, 33 % avec une démence légère
- 59 % porteurs hétérozygotes d'APOE e4
- Tous les participants ont confirmé être positifs à l'amyloïde
Les résultats sont attendus au T4 2024, avec une étude d'extension à long terme en cours. Les données de base confirment une population d'étude représentative pour tester les effets d'AL002 dans la MA précoce.
Alector präsentierte die Basismerkmale der INVOKE-2 Phase-2-Studie zu AL002, einem TREM2-Agonisten, auf der AAIC® 2024. Die Studie, die 381 Teilnehmer mit frühem Alzheimer (AD) einbezieht, ist die erste globale Phase-2-Studie zur Bewertung der Sicherheit und Wirksamkeit eines TREM2-Agonisten bei der Verlangsamung des Fortschreitens der AD. Schlüsselmerkmale:
- Medianalter: 71 Jahre (Spanne: 51-85)
- 78% der Teilnehmer sind ≥65 Jahre alt
- 50% Frauen, 94% Kaukasier
- 67% mit leichter kognitiver Beeinträchtigung, 33% mit leichter Demenz
- 59% heterozygote Träger von APOE e4
- Alle Teilnehmer wurden als amyloid-positiv bestätigt
Die Ergebnisse werden im 4. Quartal 2024 erwartet, während eine Langzeitverlängerungsstudie im Gange ist. Die Basisdaten bestätigen eine repräsentative Studienpopulation zur Prüfung der Auswirkungen von AL002 bei frühem AD.
- First global Phase 2 trial exploring a novel TREM2 agonist in early Alzheimer's disease
- Baseline characteristics confirm enrollment of intended population with early AD
- Nearly all eligible participants rolled over into the long-term extension study
- Phase 1 study showed dose-dependent target engagement and effects on microglial signaling biomarkers
- AL002 was well-tolerated in healthy volunteers at multiple doses in Phase 1
- Treatment-emergent brain MRI changes resembling ARIA observed in the trial
- Greater incidence and severity of ARIA-like changes in homozygous APOE e4 carriers
- Company discontinued homozygous APOE e4 carriers early in the trial
The baseline characteristics data presented for the INVOKE-2 Phase 2 clinical trial of AL002 in early Alzheimer's disease (AD) provide important insights into the study's design and potential implications. As a Medical Research Analyst, I find several aspects particularly noteworthy:
- The trial enrolled a total of 381 participants, with a median age of 71 years. This age range is appropriate for studying early AD, as the risk of developing the disease increases significantly after age 65.
- The 50/50 gender split and 94% Caucasian demographic may limit the generalizability of results to other populations. Future studies should aim for greater diversity to ensure broader applicability.
- The inclusion of both mild cognitive impairment (67%) and mild dementia (33%) due to AD allows for a comprehensive evaluation of AL002's efficacy across the early AD spectrum.
- The 59% heterozygous APOE e4 carrier rate is higher than the general population, which is appropriate given the increased AD risk associated with this genotype. However, the exclusion of homozygous APOE e4 carriers due to increased ARIA risk may limit our understanding of AL002's effects in this high-risk group.
- The mean amyloid PET centiloid value of 100.1 confirms significant amyloid burden in the study population, validating the inclusion of appropriate AD candidates.
While these baseline characteristics suggest a well-designed study population for testing AL002, the lack of diversity and exclusion of homozygous APOE e4 carriers may necessitate additional studies to fully understand the drug's potential across all AD populations.
From a financial perspective, the INVOKE-2 Phase 2 trial for AL002 represents a significant milestone for Alector and its collaboration with AbbVie. Here are key points to consider:
- As the first global Phase 2 trial of a TREM2 agonist in early AD, AL002 has potential first-mover advantage in this novel therapeutic approach. This could translate to substantial market share if proven effective.
- The collaboration with AbbVie, a major pharmaceutical company, provides Alector with financial support and expertise in late-stage clinical development and commercialization. This partnership mitigates some of the financial risks associated with drug development.
- The expected results in Q4 2024 will be a critical catalyst for Alector's stock. Positive outcomes could significantly boost the company's valuation, while negative results may have a substantial adverse impact.
- The high rollover rate into the long-term extension study is encouraging, potentially indicating good tolerability and perceived benefit by participants. This could bode well for future patient adherence if AL002 reaches the market.
- However, the observed ARIA in APOE e4 homozygotes and their subsequent exclusion from the trial may limit the drug's potential market size and require additional studies, potentially increasing development costs.
Investors should closely monitor the Q4 2024 readout, as it will likely have a significant impact on Alector's financial prospects and stock performance. The outcome will also influence the broader landscape of AD drug development, potentially affecting other companies in this space.
As a Biotechnology Expert, I find the INVOKE-2 trial of AL002 particularly intriguing due to its novel approach in targeting TREM2 for Alzheimer's disease treatment. Here's my analysis of the key aspects:
- AL002's mechanism as a TREM2 agonist represents a shift from traditional amyloid-β and tau-focused approaches. This aligns with the growing interest in neuroinflammation and microglial function in AD pathogenesis.
- The Phase 1 results showing dose-dependent target engagement and effects on microglial signaling biomarkers are promising. However, it's important to see if these translate to clinical benefits in Phase 2.
- The observation of ARIA, particularly in APOE e4 homozygotes, is concerning but not unexpected. Similar side effects have been seen with other AD therapies that modulate brain inflammation or amyloid clearance.
- The use of both CSF and amyloid PET for confirming amyloid positivity enhances the reliability of patient selection. The mean centiloid value of 100.1 indicates a substantial amyloid burden, appropriate for testing an AD therapy.
- The inclusion of biomarker assessments (although details are not provided) will be important for understanding AL002's mechanism of action and potentially identifying responder populations.
While the INVOKE-2 trial seems well-designed to assess AL002's efficacy, the true test will be whether modulating TREM2 can meaningfully impact AD progression. The results will have significant implications not just for Alector, but for the entire field of microglial-targeted therapies in neurodegenerative diseases.
--INVOKE-2 is the first global Phase 2 trial evaluating the safety and efficacy of a TREM2 agonist, AL002, in slowing disease progression in individuals with early Alzheimer’s disease (AD)--
--Baseline characteristics data for the INVOKE-2 study confirm a representative study population that enables testing of the effects of a novel TREM2 agonist in early AD--
SOUTH SAN FRANCISCO, Calif., July 28, 2024 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, today announced the presentation of a poster on baseline characteristics for the global INVOKE-2 Phase 2 clinical trial evaluating the safety and efficacy of AL002 in slowing disease progression in individuals with early Alzheimer’s disease (AD) at the Alzheimer's Association International Conference® 2024 (AAIC®). The conference is being held online and in Philadelphia, Pennsylvania from July 28 – August 1, 2024.
INVOKE-2 is the first global Phase 2 trial exploring a novel TREM2 agonist, AL002, in early AD. AL002 is an investigational humanized monoclonal antibody (mAb) that binds to triggering receptor expressed on myeloid cells 2 (TREM2), and it is the most advanced TREM2 agonist product candidate in clinical trials. The candidate is being developed in collaboration with AbbVie.
"The baseline characteristics of the patients in INVOKE-2 are important for assessing the quality of our double-blind, placebo-controlled Phase 2 clinical trial evaluating the safety and efficacy of AL002, the most advanced TREM2-activating candidate in clinical development for early Alzheimer’s disease,” said Gary Romano, M.D., Ph.D., Chief Medical Officer of Alector. “We are pleased that the baseline clinical assessments confirm that the INVOKE-2 trial enrolled the intended population of participants with early Alzheimer’s disease, allowing us to test Alector’s hypothesis that treatment with this first-in-class TREM2 agonist may slow disease progression.”
Baseline characteristics are important in Phase 2 trials because they ensure the reliability and interpretability of trial results, help manage patient safety, and facilitate appropriate statistical analyses. A total of 381 participants were randomized in INVOKE-2. The median age of participants was 71 years (range: 51-85 years), with
Treatment-emergent brain MRI changes resembling amyloid-related imaging abnormalities (ARIA) have been observed in the trial. These changes were of greater incidence and severity in homozygous APOE e4 carriers, and the company chose to discontinue homozygous APOE e4 carriers early in the trial. Of the 381 enrolled participants,
Additional details will be presented during the poster presentation, “Baseline Characteristics for INVOKE-2: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study Evaluating AL002 in Early Alzheimer’s Disease” (#95594) on Sunday, July 28, 2024, from 8:00 a.m. – 4:15 p.m. ET at AAIC®.
A Phase 1 study of AL002 demonstrated dose-dependent target engagement and dose-dependent effects on microglial signaling biomarkers, and the treatment was well-tolerated in healthy volunteers at multiple doses.
Results of the INVOKE-2 trial are expected in the fourth quarter of 2024, and the long-term extension (LTE) study is ongoing for those who completed the planned treatment period. Thus far, nearly all eligible participants have rolled over into the LTE study, which will facilitate better understanding of the long-term effects of AL002.
About INVOKE-2
INVOKE-2 (Clinicaltrials.gov identifier NCT04592874) is a double-blind, placebo-controlled, dose-ranging, multi-center, randomized clinical trial in patients with early AD. The trial utilizes a common close design with up to 96 weeks of randomized treatment, and all participants remain on their assigned regimen until the last participant completes 48 weeks of treatment. This design provides the opportunity to capture more observations for the primary analysis, with data collected for up to 96 weeks. Patients are randomized to three dose regimens, 15mg/kg IV/q4w, 40mg/kg IV/q4w, 60mg/kg IV/q4w, or placebo.
About AL002
AL002 is an investigational humanized monoclonal antibody that targets triggering receptor expressed on myeloid cells 2 (TREM2), a key microglial membrane receptor that senses pathological changes in the brain. Studies have identified 40 TREM2 mutations related to Alzheimer’s disease (AD), with heterozygous mutations increasing AD risk by as much as threefold.1 Reduced TREM2 function may contribute to AD and other neurodegenerative diseases. Conversely, higher levels of TREM2, as measured by cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2) are associated with lower amyloid and tau accumulation as well as attenuated cognitive and clinical decline.2,3
AL002 is designed to increase TREM2 signaling and enhance microglia proliferation, survival, and function. Binding of AL002 to the TREM2 receptor aims to trigger microglial signaling pathways, bolstering the effectiveness of microglia in protecting the brain against insults, including age-related neurodegeneration in AD. The clinical potential of AL002 is currently under investigation in clinical trials focused on evaluating its impact on AD.
Collaboration with AbbVie
In October 2017, Alector entered into a global strategic collaboration with AbbVie (NYSE: ABBV), to co-develop and commercialize therapeutics to treat Alzheimer’s disease and other neurodegenerative diseases. Under the terms of the agreement, Alector granted AbbVie an exclusive option to global development and commercialization for the AL002 TREM2 program. If AbbVie exercises its option for the program, Alector would be eligible for additional payments totaling up to
About Alector
Alector is a clinical-stage biotechnology company pioneering immuno-neurology, a novel therapeutic approach for the treatment of neurodegenerative diseases. Immuno-neurology targets immune dysfunction as a root cause of multiple pathologies that are drivers of degenerative brain disorders. Alector has discovered and is developing a broad portfolio of innate immune system programs, designed to functionally repair genetic mutations that cause dysfunction of the brain’s immune system and enable rejuvenated immune cells to counteract emerging brain pathologies. Alector’s immuno-neurology product candidates are supported by biomarkers and seek to treat indications, including Alzheimer’s disease and genetically defined frontotemporal dementia patient populations. Alector is headquartered in South San Francisco, California. For more information, visit www.alector.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include, but are not limited to, statements regarding our business plans, business strategy, product candidates, planned and ongoing preclinical studies and clinical trials, anticipated timing and detail or release of data for INVOKE-2, expected milestones, expectations of our collaborations, and expectations of our interactions with regulatory authorities. Such statements are subject to numerous risks and uncertainties, including but not limited to risks and uncertainties as set forth in Alector’s Quarterly Report on Form 10-Q filed on May 8, 2024, with the Securities and Exchange Commission (“SEC”), as well as the other documents Alector files from time to time with the SEC. These documents contain and identify important factors that could cause the actual results for Alector to differ materially from those contained in Alector’s forward-looking statements. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alector specifically disclaims any obligation to update any forward-looking statement, except as required by law.
REFERENCES
1. Mutations TREM2 | Alzforum. (n.d.). Retrieved November 29, 2023, from https://www.alzforum.org/mutations/trem2.
2. Ewers M, et al.; Alzheimer’s Disease Neuroimaging Initiative. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease. Sci Transl Med. 2019 Aug 28;11(507):eaav6221.
3. Pereira, J.B., et al. Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer’s disease pathology. Nat Aging 2, 1138–1144 (2022).
Alector Contacts:
Alector
Katie Hogan
202-549-0557
katie.hogan@alector.com
1AB (media)
Dan Budwick
973-271-6085
dan@1abmedia.com
Argot Partners (investors)
Laura Perry
212.600.1902
alector@argotpartners.com
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