Alector Announces Completion of Enrollment in the PROGRESS-AD Phase 2 Clinical Trial of AL101/GSK4527226 in Individuals with Early Alzheimer’s Disease
Alector (Nasdaq: ALEC) has completed enrollment ahead of schedule for its PROGRESS-AD Phase 2 clinical trial, evaluating AL101/GSK4527226 in early Alzheimer's disease patients. The 76-week trial, conducted in partnership with GSK, aims to assess the safety and efficacy of AL101 in slowing disease progression.
AL101 is an investigational human monoclonal antibody designed to elevate progranulin (PGRN) levels in the brain by blocking the sortilin receptor. Research has shown that reduced PGRN levels from GRN gene mutations increase Alzheimer's risk, while elevated PGRN levels demonstrate protective effects in animal models.
The randomized, double-blind, placebo-controlled study is evaluating two dose levels of AL101 administered intravenously. The trial's primary endpoint measures disease progression using the Clinical Dementia Rating Sum of Boxes (CDR®-SB), a validated instrument tracking cognitive impairments.
Alector (Nasdaq: ALEC) ha completato l'arruolamento in anticipo rispetto al previsto per il suo studio clinico di Fase 2 PROGRESS-AD, che valuta AL101/GSK4527226 in pazienti con Alzheimer precoce. Lo studio, della durata di 76 settimane e condotto in collaborazione con GSK, mira a valutare la sicurezza e l'efficacia di AL101 nel rallentare la progressione della malattia.
AL101 è un anticorpo monoclonale umano sperimentale progettato per aumentare i livelli di progranulina (PGRN) nel cervello bloccando il recettore sortilina. Le ricerche hanno dimostrato che la riduzione dei livelli di PGRN dovuta a mutazioni del gene GRN aumenta il rischio di Alzheimer, mentre livelli elevati di PGRN mostrano effetti protettivi nei modelli animali.
Lo studio randomizzato, in doppio cieco e controllato con placebo valuta due dosi di AL101 somministrate per via endovenosa. L’endpoint primario dello studio misura la progressione della malattia utilizzando il Clinical Dementia Rating Sum of Boxes (CDR®-SB), uno strumento validato per monitorare le compromissioni cognitive.
Alector (Nasdaq: ALEC) ha completado la inscripción antes de lo previsto para su ensayo clínico de fase 2 PROGRESS-AD, que evalúa AL101/GSK4527226 en pacientes con enfermedad de Alzheimer temprana. El ensayo de 76 semanas, realizado en colaboración con GSK, tiene como objetivo evaluar la seguridad y eficacia de AL101 para ralentizar la progresión de la enfermedad.
AL101 es un anticuerpo monoclonal humano en investigación diseñado para aumentar los niveles de progranulina (PGRN) en el cerebro bloqueando el receptor sortilina. Las investigaciones han demostrado que niveles reducidos de PGRN debido a mutaciones en el gen GRN aumentan el riesgo de Alzheimer, mientras que niveles elevados de PGRN muestran efectos protectores en modelos animales.
El estudio aleatorizado, doble ciego y controlado con placebo está evaluando dos dosis de AL101 administradas por vía intravenosa. El objetivo principal del ensayo mide la progresión de la enfermedad usando la escala Clinical Dementia Rating Sum of Boxes (CDR®-SB), un instrumento validado para seguir el deterioro cognitivo.
Alector (나스닥: ALEC)는 초기 알츠하이머 환자를 대상으로 AL101/GSK4527226을 평가하는 PROGRESS-AD 2상 임상시험의 등록을 예정보다 조기에 완료했습니다. GSK와 협력하여 진행되는 이 76주간의 임상시험은 AL101의 안전성과 질병 진행 속도 지연 효과를 평가하는 것을 목표로 합니다.
AL101은 소르틸린 수용체를 차단하여 뇌 내 프로그라뉼린(PGRN) 수치를 높이도록 설계된 연구용 인간 단일클론항체입니다. 연구에 따르면 GRN 유전자 돌연변이로 인한 PGRN 수치 감소는 알츠하이머 위험을 증가시키는 반면, PGRN 수치 상승은 동물 모델에서 보호 효과를 나타냅니다.
무작위 배정, 이중 맹검, 위약 대조 연구는 정맥 주사로 투여되는 AL101 두 가지 용량을 평가합니다. 임상시험의 주요 평가 지표는 인지 장애를 추적하는 검증된 도구인 Clinical Dementia Rating Sum of Boxes(CDR®-SB)를 사용하여 질병 진행을 측정합니다.
Alector (Nasdaq : ALEC) a terminé le recrutement en avance pour son essai clinique de phase 2 PROGRESS-AD, évaluant AL101/GSK4527226 chez des patients atteints d'Alzheimer précoce. Cet essai de 76 semaines, réalisé en partenariat avec GSK, vise à évaluer la sécurité et l'efficacité d'AL101 dans le ralentissement de la progression de la maladie.
AL101 est un anticorps monoclonal humain expérimental conçu pour augmenter les niveaux de progranuline (PGRN) dans le cerveau en bloquant le récepteur sortiline. Les recherches ont montré que des niveaux réduits de PGRN dus à des mutations du gène GRN augmentent le risque d'Alzheimer, tandis que des niveaux élevés de PGRN ont des effets protecteurs dans des modèles animaux.
Cette étude randomisée, en double aveugle et contrôlée par placebo évalue deux doses d'AL101 administrées par voie intraveineuse. Le critère principal de l'essai mesure la progression de la maladie à l'aide du Clinical Dementia Rating Sum of Boxes (CDR®-SB), un outil validé pour suivre les troubles cognitifs.
Alector (Nasdaq: ALEC) hat die Rekrutierung für seine PROGRESS-AD Phase-2-Studie vorzeitig abgeschlossen. Diese Studie untersucht AL101/GSK4527226 bei Patienten mit frühem Alzheimer. Die 76-wöchige Studie, die in Zusammenarbeit mit GSK durchgeführt wird, zielt darauf ab, die Sicherheit und Wirksamkeit von AL101 zur Verlangsamung des Krankheitsverlaufs zu bewerten.
AL101 ist ein experimenteller humaner monoklonaler Antikörper, der entwickelt wurde, um die Progranulin (PGRN)-Spiegel im Gehirn durch Blockade des Sortilin-Rezeptors zu erhöhen. Studien zeigen, dass verringerte PGRN-Spiegel aufgrund von GRN-Genmutationen das Alzheimer-Risiko erhöhen, während erhöhte PGRN-Spiegel in Tiermodellen schützende Effekte zeigen.
Die randomisierte, doppelblinde, placebokontrollierte Studie bewertet zwei Dosierungsstufen von AL101, die intravenös verabreicht werden. Der primäre Endpunkt der Studie misst den Krankheitsverlauf anhand der Clinical Dementia Rating Sum of Boxes (CDR®-SB), einem validierten Instrument zur Erfassung kognitiver Beeinträchtigungen.
- Early completion of Phase 2 trial enrollment indicates strong execution
- Partnership with major pharmaceutical company GSK strengthens development capabilities
- Scientific evidence supports the drug's mechanism of action through animal studies
- No efficacy data available yet from the Phase 2 trial
- Still in mid-stage development with significant time before potential commercialization
Insights
Alector's accelerated trial enrollment for AL101 in Alzheimer's is positive but milestone-based progress; real value hinges on efficacy data.
Alector's announcement of completed enrollment in their PROGRESS-AD Phase 2 trial represents a meaningful operational milestone in the development of AL101, especially considering the enrollment was finished ahead of schedule. This achievement is particularly significant for a company with Alector's modest market capitalization of just under
The company's focus on progranulin elevation via sortilin receptor blockade offers a differentiated mechanism in the increasingly crowded Alzheimer's landscape. This approach is supported by genetic evidence showing that reduced progranulin levels increase Alzheimer's risk, while elevated levels appear protective in preclinical models.
The GSK collaboration brings critical validation and resources. The trial design includes the gold-standard CDR-SB as the primary endpoint, which is the same measure used in successful recent Alzheimer's trials. The 76-week duration is appropriate for detecting meaningful clinical changes.
However, investors should recognize that accelerated enrollment doesn't necessarily correlate with improved efficacy prospects. While operational execution deserves recognition, the true value inflection point remains the eventual efficacy readout. With the trial now fully enrolled, we're one step closer to understanding whether this novel mechanism can deliver clinical benefits.
Early trial enrollment completion suggests strong investigator interest and efficient execution, but efficacy remains the ultimate question.
Completing enrollment ahead of schedule in the PROGRESS-AD trial demonstrates strong operational execution and likely reflects high investigator interest in Alector's approach. For context, many CNS trials face significant enrollment challenges, especially in Alzheimer's disease, where patient identification and screening complexity often cause delays.
The trial's design merits attention - it's a randomized, double-blind, placebo-controlled study evaluating two dose levels of AL101. The use of CDR-SB as the primary endpoint aligns with regulatory expectations and recent successful Alzheimer's trials. The 76-week duration is sufficient to potentially capture meaningful clinical changes.
From a mechanism perspective, targeting progranulin elevation represents a novel approach distinct from amyloid-clearing or tau-targeting therapies. The biological rationale is supported by genetic evidence linking progranulin levels to Alzheimer's risk.
While operational milestones like enrollment completion typically reflect positively on a program's execution, they provide insight into the ultimate question of efficacy. The next critical milestone will be data readout, which will determine whether AL101's mechanism translates to meaningful clinical benefits. Until then, this represents positive progress in advancing a first-in-class approach to addressing this devastating neurodegenerative condition.
--76-week trial is evaluating the safety and efficacy of a progranulin-elevating candidate in slowing disease progression--
--Enrollment completed ahead of schedule--
SOUTH SAN FRANCISCO, Calif., April 17, 2025 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a late-stage clinical biotechnology company focused on developing therapies to counteract the devastating progression of neurodegeneration, today announced the completion of enrollment in PROGRESS-AD, a 76-week Phase 2 clinical trial evaluating the safety and efficacy of AL101/GSK4527226 in slowing disease progression in individuals with early Alzheimer’s disease (AD).
Alector and GSK are co-developing AL101, an investigational human monoclonal antibody designed to block and downregulate the sortilin receptor to elevate progranulin (PGRN) levels in the brain. Modest reductions in PGRN levels due to GRN gene mutations have been shown to be associated with an increased risk of developing AD.1, 2, 3 Conversely, elevated PGRN levels have been shown to be protective in animal models of AD.4
“In partnership with GSK, we are pleased to announce the completion of enrollment ahead of schedule in the PROGRESS-AD Phase 2 clinical trial of AL101, marking an important milestone in our pursuit of developing first-in-class therapies for Alzheimer’s disease,” said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. “This achievement brings us one step closer to assessing the potential of AL101 in slowing disease progression and to furthering our understanding of AL101’s effects on individuals living with this devastating condition. We remain committed to advancing our progranulin-elevating candidate and evaluating its impact in the ongoing trial.”
PROGRESS-AD is a randomized, double-blind, placebo-controlled Phase 2 clinical trial of AL101, which GSK is conducting at multiple sites globally. Two dose levels of AL101 are being evaluated in the trial, with participants randomized to receive either AL101 or placebo intravenously. The primary endpoint of the study is disease progression as measured by the Clinical Dementia Rating Sum of Boxes (CDR®-SB). The CDR-SB is a validated instrument that tracks the progression of cognitive impairments in various categories. The trial also measures other clinical and functional outcome assessments.
Additional information about PROGRESS-AD (NCT06079190) may be found at ClinicalTrials.gov.
About AL101/ GSK4527226
AL101/GSK4527226 is an investigational human monoclonal antibody designed to block and downregulate the sortilin receptor to elevate progranulin (PGRN) levels in the brain. PGRN, a protein encoded by the GRN gene, regulates lysosomal function, neuronal survival, and inflammation. The protein is genetically linked to multiple neurodegenerative disorders. Alector and GSK are co-developing AL101 for the potential treatment of early Alzheimer’s disease (AD), and it may also be evaluated for other indications, including Parkinson’s disease (PD). Given PGRN's genetic association with neurodegeneration, elevating PGRN levels may provide a potential therapeutic approach that offers broad neuroprotection in both AD and PD.
Collaboration with GSK
In July 2021, Alector entered into a collaboration and license agreement with GSK (LSE/NYSE: GSK) to collaborate on the global development and commercialization of progranulin-elevating monoclonal antibodies, including latozinemab and AL101/GSK4527226. Under the terms of the GSK agreement, Alector received
About Alector
Alector is a late-stage clinical biotechnology company focused on developing therapies to counteract the devastating progression of neurodegenerative diseases. Leveraging the principles of genetics, immunology, and neuroscience, the company is advancing a portfolio of genetically validated programs that aim to remove toxic proteins, replace deficient proteins, and restore immune and nerve cell function. Supported by biomarkers, Alector’s product candidates seek to treat a range of indications, such as frontotemporal dementia, Alzheimer’s disease, and Parkinson's disease. The company is also developing Alector Brain Carrier (ABC), a proprietary blood-brain barrier platform, which is being selectively applied to its next-generation product candidates and research pipeline. ABC aims to enhance the delivery of therapeutics, achieve deeper brain penetration and efficacy at lower doses, and ultimately improve patient outcomes while reducing costs. Alector is headquartered in South San Francisco, California. For more information, please 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, blood-brain barrier technology platform, research and preclinical pipeline, planned and ongoing preclinical studies and clinical trials, anticipated timing of PROGRESS-AD, expected milestones, expectations of our collaboration with GSK, expectations of our interactions with regulatory authorities, and financial and cash guidance. Such statements are subject to numerous risks and uncertainties, including but not limited to risks and uncertainties as set forth in Alector’s Annual Report on Form 10-K filed for 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
- Bellenguez, C., et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat. Genet. 2022, 54, 412–436.
- Brouwers, N, et al. Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease. Neurology. 2008, 71, 656–664.
- Fenoglio, C, et al. Rs5848 variant influences GRN mRNA levels in brain and peripheral mononuclear cells in patients with Alzheimer’s disease. J. Alzheimer’s Dis. 2009, 18, 603–612
- Minami, S.S; et al. Progranulin protects against amyloid beta deposition and toxicity in Alzheimer’s disease mouse models. Nat. Med. 2014, 20, 1157–1164.
Alector Contacts:
Alector
Katie Hogan
202-549-0557
katie.hogan@alector.com
Argot Partners (media)
David Rosen
646-461-6387
alector@argotpartners.com
Argot Partners (investors)
Laura Perry
212-600-1902
alector@argotpartners.com
FAQ
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