ACELYRIN, INC. Announces Additional Phase 2 Data and Phase 3 Program Design for Lonigutamab in Thyroid Eye Disease
ACELYRIN (SLRN) has announced additional Phase 2 data and Phase 3 program design for lonigutamab in Thyroid Eye Disease (TED). The Phase 2 trial demonstrated clinically meaningful improvements across TED manifestations, including proptosis, Clinical Activity Score, and diplopia. The drug showed significant response rates with a 50 mg loading and 25 mg weekly subcutaneous dose.
The Phase 3 LONGITUDE program will include two global trials across ~350 patients, evaluating a 100 mg loading dose followed by 50 mg every two weeks. The trials will begin in Q1 2025, with topline data expected in second half of 2026. LONGITUDE-1 and 2 will study both 'active' and 'chronic' TED patients, with primary endpoints measuring proptosis response rate at 24 weeks.
The company received FDA alignment on the Phase 3 trial designs in Q3 2024 and maintains a cash runway through mid-2027.
ACELYRIN (SLRN) ha annunciato ulteriori dati della Fase 2 e il design del programma di Fase 3 per il lonigutamab nella Malattia dell'Occhio Tireoidiano (TED). La sperimentazione di Fase 2 ha mostrato miglioramenti clinicamente significativi in varie manifestazioni della TED, inclusi proptosi, punteggio di attività clinica e diplopia. Il farmaco ha mostrato tassi di risposta significativi con un dosaggio di carico di 50 mg e una dose sottocutanea settimanale di 25 mg.
Il programma di Fase 3 LONGITUDE includerà due studi globali su circa 350 pazienti, valutando una dose di carico di 100 mg seguita da 50 mg ogni due settimane. Gli studi inizieranno nel primo trimestre del 2025, con dati preliminari attesi nella seconda metà del 2026. LONGITUDE-1 e 2 studieranno sia pazienti con TED 'attiva' che 'cronica', con obiettivi primari misuranti il tasso di risposta della proptosi a 24 settimane.
La società ha ricevuto l'allineamento della FDA sui design degli studi di Fase 3 nel terzo trimestre del 2024 e mantiene una liquidità sufficiente fino a metà 2027.
ACELYRIN (SLRN) ha anunciado datos adicionales de la Fase 2 y el diseño del programa de Fase 3 para el lonigutamab en la Enfermedad del Ojo Tiroideo (TED). El ensayo de Fase 2 demostró mejoras clínicamente significativas en varias manifestaciones de TED, incluyendo proptosis, puntaje de actividad clínica y diplopía. El medicamento mostró tasas de respuesta significativas con una dosis de carga de 50 mg y una dosis subcutánea semanal de 25 mg.
El programa de Fase 3 LONGITUDE incluirá dos ensayos globales en aproximadamente 350 pacientes, evaluando una dosis de carga de 100 mg seguida de 50 mg cada dos semanas. Los ensayos comenzarán en el primer trimestre de 2025, con datos preliminares esperados en la segunda mitad de 2026. LONGITUDE-1 y 2 estudiarán tanto a pacientes con TED 'activa' como 'crónica', con los objetivos primarios midiendo la tasa de respuesta de la proptosis a las 24 semanas.
La empresa recibió alineación de la FDA sobre los diseños de los ensayos de Fase 3 en el tercer trimestre de 2024 y mantiene una liquidez suficiente hasta mediados de 2027.
ACELYRIN (SLRN)은 갑상선 안병(TED)에서 lonigutamab에 대한 추가적인 2상 데이터 및 3상 프로그램 설계를 발표했습니다. 2상 시험에서는 임상적으로 의미 있는 개선이 TED의 다양한 증상에서 나타났습니다. 여기에는 안구돌출, 임상 활동 점수 및 복시가 포함됩니다. 이 약물은 50mg의 하중 용량과 매주 25mg의 피하 주사 용량으로 유의미한 반응률을 보였습니다.
3상 LONGITUDE 프로그램은 약 350명의 환자를 대상으로 진행되는 두 개의 글로벌 시험을 포함하며, 100mg의 하중 용량을 투여한 후 2주마다 50mg을 평가합니다. 이 시험은 2025년 1분기부터 시작되며, 2026년 하반기에 topline 데이터가 예상됩니다. LONGITUDE-1 및 LONGITUDE-2는 '활성' 및 '만성' TED 환자를 연구하며, 주요 목표는 24주 후의 안구돌출 반응률을 측정하는 것입니다.
회사는 2024년 3분기에 3상 시험 디자인에 대한 FDA의 승인을 받았으며, 2027년 중반까지 자금이 충분히 확보되어 있습니다.
ACELYRIN (SLRN) a annoncé des données supplémentaires de la phase 2 et le design du programme de phase 3 pour le lonigutamab dans la Maladie de l'Œil Thyroïdien (TED). L'essai de phase 2 a démontré des améliorations cliniquement significatives dans diverses manifestations de la TED, y compris la proptose, le score d'activité clinique et la diplopie. Le médicament a montré des taux de réponse significatifs avec une dose de charge de 50 mg et une dose sous-cutanée hebdomadaire de 25 mg.
Le programme de phase 3 LONGITUDE comprendra deux essais globaux sur environ 350 patients, évaluant une dose de charge de 100 mg suivie de 50 mg toutes les deux semaines. Les essais commenceront au premier trimestre 2025, avec des données préliminaires attendues dans la seconde moitié de 2026. LONGITUDE-1 et 2 étudieront à la fois des patients avec une TED 'active' et 'chronique', avec des objectifs principaux mesurant le taux de réponse de proptose à 24 semaines.
L'entreprise a reçu l'alignement de la FDA sur les conceptions d'essais de phase 3 au troisième trimestre 2024 et maintient une liquidité suffisante jusqu'à la mi-2027.
ACELYRIN (SLRN) hat zusätzliche Daten der Phase 2 und das Design des Phase-3-Programms für Lonigutamab bei der Schilddrüsenaugenkrankheit (TED) bekannt gegeben. Die Phase-2-Studie zeigte klinisch signifikante Verbesserungen bei den verschiedenen Manifestationen von TED, einschließlich Proptose, klinischem Aktivitätsindex und Diplopie. Das Medikament zeigte signifikante Ansprechraten mit einer Lade-Dosis von 50 mg und einer wöchentlichen subkutanen Dosis von 25 mg.
Das Phase-3-LONGITUDE-Programm wird zwei globale Studien mit insgesamt ~350 Patienten umfassen, die eine Lade-Dosis von 100 mg gefolgt von 50 mg alle zwei Wochen bewerten. Die Studien beginnen im ersten Quartal 2025, mit ersten Ergebnissen, die für die zweite Hälfte des Jahres 2026 erwartet werden. LONGITUDE-1 und 2 werden sowohl 'aktive' als auch 'chronische' TED-Patienten untersuchen, wobei die primären Endpunkte die Proptose-Ansprechrate nach 24 Wochen messen.
Das Unternehmen erhielt im dritten Quartal 2024 eine Abstimmung mit der FDA zu den Phase-3-Studiengestaltungen und hat bis Mitte 2027 ausreichend finanzielle Mittel.
- Phase 2 trial showed efficacy comparable to IV standard of care with better safety profile
- No reported cases of hearing impairment, hyperglycemia, or menstrual disorders
- FDA alignment received on Phase 3 trial design
- Cash runway extends through mid-2027
- Phase 3 trials won't start until Q1 2025
- Topline data not expected until second half of 2026
Insights
The Phase 2 data for lonigutamab demonstrates compelling clinical efficacy with a potentially superior safety profile compared to existing TED treatments. Key differentiators include no reported cases of hearing impairment, hyperglycemia, or menstrual disorders - significant safety advantages over current therapies. The subcutaneous administration route at 100mg loading dose followed by 50mg biweekly achieves therapeutic concentrations rapidly while offering improved convenience over IV alternatives.
The Phase 3 LONGITUDE program design is robust, with two global trials across ~350 patients. The 2:1 randomization and 24-week placebo-controlled period, followed by active treatment through 52 weeks, will provide comprehensive efficacy and safety data. The inclusion of both active and chronic TED patients enhances real-world applicability. Expected topline data in H2 2026 positions ACELYRIN well within the competitive landscape.
The market implications are substantial given TED's current treatment limitations. Lonigutamab's subcutaneous administration and promising safety profile could capture significant market share from existing IV therapies. The cash runway through mid-2027 adequately covers the critical Phase 3 readout period, reducing near-term financing risks. FDA alignment on the Phase 3 design significantly de-risks the regulatory pathway.
The competitive positioning is strong - combining standard-of-care level efficacy with improved safety and convenience could drive rapid market adoption if approved. The comprehensive Phase 3 program, including both active and chronic TED patients, could support broad label claims and maximize market potential. This represents a major catalyst for ACELYRIN, with the potential to transform their market position in immunology.
Totality of data observed with subcutaneous lonigutamab in Thyroid Eye Disease (TED) patients demonstrate potential for efficacy in line with standard of care and a more favorable safety profile
Conducted positive end of Phase 2 FDA meeting; Phase 3 program expected to be initiated in Q1 2025
Topline Phase 3 data expected in second half of 2026; cash runway expected through mid-2027
Conference call to review unmet need in TED, new Phase 2 data and Phase 3 program design to be held today, January 6, 2025, at 4:30 PM ET
LOS ANGELES, Jan. 06, 2025 (GLOBE NEWSWIRE) -- ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today announced additional Phase 2 data and the Phase 3 program design for lonigutamab in Thyroid Eye Disease (TED). The Company will host a virtual investor event today, Monday, January 6, 2025 at 4:30 PM ET. To register, click here.
“Lonigutamab, with its unique mechanism of action, is the first subcutaneous anti-IGF-1R to have demonstrated robust efficacy in TED patients comparable to the IV administered standard of care. We are further encouraged by its potential for a best-in-class safety profile with no reported cases of hearing impairment, hyperglycemia or menstrual disorders to date,” said Mina Kim, Chief Executive Officer of ACELYRIN. “Our innovative dose exploration work in TED patients gives us confidence our Phase 3 dose has the potential to optimize patient benefit and risk and transform the TED treatment paradigm. Our registrational program is designed for real-world patients and focused on addressing the significant unmet needs in TED.”
Additional Phase 2 data
In the newly announced data from the ongoing Phase 2 trial in TED, lonigutamab demonstrated:
- Clinically meaningful and competitive improvements across all manifestations of TED, including proptosis, Clinical Activity Score (CAS) and diplopia, as well as the Graves Ophthalmopathy-Quality of Life (GO-QoL) tool:
- Significant proptosis response rate shown with a 50 mg loading and 25 mg weekly (QW) subcutaneous dose of lonigutamab
- Efficacy achieved with lower levels of exposure than seen with IV-administered anti-IGF-1R agents
- No cases of hearing impairment as measured by audiogram, hyperglycemia or menstrual disorders in TED patients reported to date at any dose level
- 100 mg loading dose achieves target therapeutic concentration within days
Phase 3 LONGITUDE Program
ACELYRIN today also announced the design for its Phase 3 LONGITUDE program, which is informed by significant dose ranging evaluation of subcutaneous lonigutamab in TED patients. Initiation of the Phase 3 program is expected this quarter and topline data are expected in the second half of 2026.
LONGITUDE-1 and 2 will be conducted across ~350 patients in two global double-masked, placebo-controlled trials to evaluate the safety and efficacy of a subcutaneously delivered 100 mg loading dose of lonigutamab followed by 50 mg every two weeks. Patients will be randomized 2:1 to either lonigutamab or placebo arms during the first 24 weeks, and the primary endpoint in both trials will be proptosis response rate at 24 weeks. All patients will receive lonigutamab after 24 weeks through to 52 weeks of treatment, which is designed to potentially enable longer-term treatment.
Both LONGITUDE-1 and LONGITUDE-2 will evaluate “active” TED patients and “chronic” TED patients, with LONGITUDE-1 enrolling a minimum of 81 active patients. The primary endpoint for LONGITUDE-1 will be proptosis response rate at 24 weeks for active patients, with a secondary endpoint of proptosis response rate at 24 weeks for all enrolled patients. LONGITUDE-2 will recruit both active and chronic TED patients and have no minimum number of required active patients. The primary endpoint for LONGITUDE-2 will be proptosis response rate at 24 weeks for all patients. Secondary endpoints for both trials include CAS, diplopia response and GO-QoL at 24 weeks.
As previously announced, ACELYRIN held an End of Phase 2 (EOP2) meeting with the United States Food and Drug Administration (FDA) in Q3 2024 and gained alignment on the proposed LONGITUDE-1 and LONGITUDE-2 Phase 3 trial designs.
Shep Mpofu, M.D., Chief Medical Officer at ACELYRIN, added, “We are excited about the data generated in our Phase 1/2 trial and the potential for lonigutamab to change the treatment paradigm for TED patients. We look forward to working closely with clinicians around the world to rapidly initiate and enroll the Phase 3 LONGITUDE program starting in Q1 2025 for the benefit of TED patients. Our Phase 3 study is designed to address the significant unmet needs of patients, and we believe lonigutamab has the potential to be a more effective, safer and more convenient alternative to the current standard of care.”
Webcast and Conference Call Information
ACELYRIN will host a webcast today, January 6, 2025, at 4:30pm ET featuring Dr. Andrea Kossler of the Stanford University School of Medicine and Dr. Prem Subramanian of the University of Colorado School of Medicine who will join company management to discuss these new lonigutamab Phase 2 data and the planned design for the Phase 3 program for the treatment of TED. A live question and answer session will follow the formal presentations. The live webcast of the conference call can be accessed in the “Events & Presentations” section of ACELYRIN’s website at www.acelyrin.com. A recording of the webcast will be available and archived on the Company’s website for approximately 30 days.
About Thyroid Eye Disease
Thyroid Eye Disease (TED) is a vision-threatening autoimmune disease in which there is both inflammation and expansion of the tissues behind the eye, resulting in eye bulging, known as proptosis, and the subsequent inability to close the eyelids. Double vision, or diplopia, can occur, as well as the potential for compression of the optic nerve, which can lead to blindness. Thus, TED is a progressive, chronic inflammatory disease. More than 100,000 people in the United States are estimated to suffer from TED.
About Lonigutamab
Lonigutamab is a humanized IgG1 monoclonal antibody targeting the insulin-like growth factor 1 (IGF-1) receptor and is delivered subcutaneously. Relative to standard of care, lonigutamab binds to a distinct epitope, which results in internalization of the receptor within minutes. The characteristics of lonigutamab that enable subcutaneous delivery also enable the potential for longer-term, convenient dosing, which can potentially improve depth and durability of clinical response.
About ACELYRIN
ACELYRIN, INC. (Nasdaq: SLRN) is focused on providing patients life-changing new treatment options by identifying, acquiring, and accelerating the development and commercialization of transformative medicines. ACELYRIN’s lead program, lonigutamab, is a subcutaneously delivered monoclonal antibody targeting IGF-1R being investigated for the treatment of thyroid eye disease (TED).
For more information about ACELYRIN, visit us at www.acelyrin.com or follow us on LinkedIn and X.
Forward Looking Statements
This press release contains forward-looking statements including, but not limited to, statements related to ACELYRIN’s expectations regarding its anticipated development activities including the planned design and initiation of ACELYRIN’s planned Phase 3 clinical trial of lonigutamab, the clinical data to be generated from ACELYRIN’s Phase 3 clinical trial of lonigutamab and the timing of the availability of such data, the characteristics of lonigutamab, including its mechanism of action, its potential efficacy and safety profile (including as compared to other products and product candidates), ACELYRIN’s interactions with regulatory authorities, ACELYRIN’s expectations regarding its cash runway, and other statements that are not historical fact. These forward-looking statements are based on ACELYRIN’s current plans, objectives and projections, and are inherently subject to risks and uncertainties that may cause ACELYRIN’s actual results to materially differ from those anticipated in such forward-looking statements. Such risks and uncertainties include, without limitation, those associated with the successful completion of development and regulatory activities with respect to ACELYRIN’s product candidates; maintaining and defending intellectual property protection; delays or failures to secure adequate supply of its product candidates; ACELYRIN’s failure to realize the expected benefits of its acquisition of additional programs; legal proceedings, government investigations or other actions; macroeconomic conditions; market volatility; and other risks and uncertainties affecting ACELYRIN including those described from time to time under the caption “Risk Factors” and elsewhere in ACELYRIN’s current and future reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2024. Forward-looking statements contained in this press release are made as of this date, and ACELYRIN undertakes no duty to update such information except as required under applicable law.
ACELYRIN Contacts:
Tyler Marciniak
Vice President of Investor Relations and Corporate Operations
investors@acelyrin.com
media@acelyrin.com
FAQ
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