Astria Therapeutics Initiates ALPHA-ORBIT Phase 3 Pivotal Trial of Navenibart in Hereditary Angioedema
Astria Therapeutics (NASDAQ: ATXS) has initiated the ALPHA-ORBIT Phase 3 pivotal trial of navenibart for hereditary angioedema (HAE). The global, randomized, double-blind, placebo-controlled study will evaluate the drug's efficacy and safety over 6 months in up to 135 adults and 10 adolescents with HAE Type 1 or 2.
The trial features three dosing arms for adults: 600mg followed by 300mg every 3 months (Q3M), 600mg every 6 months (Q6M), and 600mg Q3M, plus placebo. Adolescents will receive 600mg followed by 300mg Q3M. The primary endpoint is time-normalized monthly HAE attacks at 6 months.
The Phase 3 program design was based on positive Phase 1b/2 ALPHA-STAR trial results, which demonstrated 90-95% reduction in mean monthly attack rate and up to 67% attack-free rate over 6 months. Top-line results are expected in early 2027.
Astria Therapeutics (NASDAQ: ATXS) ha avviato il trial pivotale di Fase 3 ALPHA-ORBIT per il navenibart, destinato all'angioedema ereditario (HAE). Lo studio globale, randomizzato, in doppio cieco e controllato con placebo valuterà l'efficacia e la sicurezza del farmaco per un periodo di 6 mesi su un massimo di 135 adulti e 10 adolescenti con HAE di Tipo 1 o 2.
Il trial prevede tre bracci di dosaggio per gli adulti: 600 mg seguiti da 300 mg ogni 3 mesi (Q3M), 600 mg ogni 6 mesi (Q6M) e 600 mg Q3M, più placebo. Gli adolescenti riceveranno 600 mg seguiti da 300 mg Q3M. L'endpoint primario è il numero di attacchi di HAE normalizzato per tempo su base mensile a 6 mesi.
Il design del programma di Fase 3 si basa sui risultati positivi del trial di Fase 1b/2 ALPHA-STAR, che ha dimostrato una riduzione del 90-95% nella media mensile degli attacchi e fino al 67% di tasso senza attacchi in 6 mesi. I risultati preliminari sono attesi all'inizio del 2027.
Astria Therapeutics (NASDAQ: ATXS) ha iniciado el ensayo pivotal de Fase 3 ALPHA-ORBIT para el navenibart, destinado al angioedema hereditario (HAE). El estudio global, aleatorizado, doble ciego y controlado con placebo evaluará la eficacia y seguridad del fármaco durante 6 meses en hasta 135 adultos y 10 adolescentes con HAE Tipo 1 o 2.
El ensayo cuenta con tres grupos de dosificación para adultos: 600 mg seguidos de 300 mg cada 3 meses (Q3M), 600 mg cada 6 meses (Q6M) y 600 mg Q3M, más placebo. Los adolescentes recibirán 600 mg seguidos de 300 mg Q3M. El objetivo primario es el número de ataques de HAE normalizado por tiempo mensualmente a los 6 meses.
El diseño del programa de Fase 3 se basó en los resultados positivos del ensayo de Fase 1b/2 ALPHA-STAR, que demostró una reducción del 90-95% en la tasa media mensual de ataques y hasta un 67% de tasa libre de ataques en 6 meses. Se esperan resultados preliminares a principios de 2027.
Astria Therapeutics (NASDAQ: ATXS)는 유전성 혈관부종(HAE)을 위한 navenibart의 3상 ALPHA-ORBIT 주요 임상을 시작했습니다. 이 글로벌, 무작위, 이중 맹검, 위약 대조 연구는 HAE 1형 또는 2형을 가진 최대 135명의 성인과 10명의 청소년에서 약물의 효능과 안전성을 6개월 동안 평가할 것입니다.
임상 시험은 성인을 위한 세 가지 용량 그룹을 포함합니다: 600mg 후 3개월마다 300mg(Q3M), 6개월마다 600mg(Q6M), 그리고 600mg Q3M과 위약입니다. 청소년은 600mg 후 3개월마다 300mg을 받게 됩니다. 주요 목표는 6개월 동안의 시간 정규화된 월별 HAE 공격 횟수입니다.
3상 프로그램 설계는 1b/2상 ALPHA-STAR 시험의 긍정적인 결과를 기반으로 하며, 이는 평균 월별 공격률을 90-95% 감소시키고 6개월 동안 최대 67%의 공격 없는 비율을 보여주었습니다. 주요 결과는 2027년 초에 발표될 예정입니다.
Astria Therapeutics (NASDAQ: ATXS) a lancé l'essai pivot de Phase 3 ALPHA-ORBIT pour le navenibart, destiné à l'angioedème héréditaire (HAE). L'étude mondiale, randomisée, en double aveugle et contrôlée par placebo évaluera l'efficacité et la sécurité du médicament sur une période de 6 mois chez jusqu'à 135 adultes et 10 adolescents atteints de HAE de type 1 ou 2.
L'essai comprend trois groupes de dosage pour les adultes : 600 mg suivis de 300 mg tous les 3 mois (Q3M), 600 mg tous les 6 mois (Q6M) et 600 mg Q3M, plus placebo. Les adolescents recevront 600 mg suivis de 300 mg Q3M. Le critère principal est le nombre d'attaques d'HAE normalisé par le temps sur une base mensuelle à 6 mois.
Le design du programme de Phase 3 est basé sur les résultats positifs de l'essai de Phase 1b/2 ALPHA-STAR, qui a montré une réduction de 90-95 % du taux d'attaques mensuelles moyennes et jusqu'à 67 % de taux sans attaque sur 6 mois. Les résultats préliminaires sont attendus début 2027.
Astria Therapeutics (NASDAQ: ATXS) hat die entscheidende Phase-3-Studie ALPHA-ORBIT für Navenibart zur Behandlung von hereditärem Angioödem (HAE) gestartet. Die globale, randomisierte, doppelblinde, placebo-kontrollierte Studie wird die Wirksamkeit und Sicherheit des Medikaments über einen Zeitraum von 6 Monaten bei bis zu 135 Erwachsenen und 10 Jugendlichen mit HAE Typ 1 oder 2 bewerten.
Die Studie umfasst drei Dosierungsgruppen für Erwachsene: 600 mg, gefolgt von 300 mg alle 3 Monate (Q3M), 600 mg alle 6 Monate (Q6M) und 600 mg Q3M plus Placebo. Jugendliche erhalten 600 mg, gefolgt von 300 mg Q3M. Der primäre Endpunkt ist die zeitnormalisierte monatliche Anzahl von HAE-Attacken nach 6 Monaten.
Das Design des Phase-3-Programms basiert auf den positiven Ergebnissen der Phase-1b/2-Studie ALPHA-STAR, die eine Reduktion der durchschnittlichen monatlichen Angriffszahl um 90-95% und eine bis zu 67% Attacken-freie Rate über 6 Monate zeigte. Die vorläufigen Ergebnisse werden Anfang 2027 erwartet.
- Phase 1b/2 showed strong efficacy with 90-95% attack reduction
- Up to 67% of patients attack-free over 6 months in Phase 1b/2
- Potential for infrequent dosing (2-4 times/year)
- Advancing to Phase 3 trial following positive early results
- Long wait for Phase 3 results (early 2027)
- Still requires clinical validation in larger Phase 3 study
Insights
Astria Therapeutics' initiation of the ALPHA-ORBIT Phase 3 trial for navenibart represents a significant milestone in their clinical development strategy and positions the company to potentially disrupt the $2+ billion global HAE market.
The trial design directly addresses a key unmet need in HAE management - treatment burden. Current market leaders require significantly more frequent administration: Takeda's Takhzyro (lanadelumab) requires bi-weekly or monthly injections, and BioCryst's Orladeyo (berotralstat) requires daily oral dosing. Navenibart's potential for quarterly or biannual administration would represent a dramatic improvement in patient convenience if efficacy is maintained.
The Phase 1b/2 results showing 90-95% attack reduction and up to 67% attack-free rates are particularly compelling. These efficacy metrics are competitive with or potentially superior to current standards of care, suggesting navenibart could capture significant market share if Phase 3 results confirm these findings.
From a financial perspective, this Phase 3 program will accelerate Astria's cash burn. With a 2027 readout timeline, investors should closely monitor the company's balance sheet and potential need for additional capital raises before reaching this critical inflection point. The company will likely need to secure additional funding or strategic partnerships to support both the completion of clinical development and potential commercialization efforts.
For investors, this Phase 3 initiation transforms Astria from an early-clinical to a late-stage development company with a potential best-in-class therapy for a well-established market. However, execution risks remain significant given the lengthy timeline to data readout and the competitive nature of the HAE space, where several companies are pursuing novel approaches to attack prevention.
-- Trial Designed to Demonstrate Efficacy and Safety of Every 3- and Every 6-Month Administration in a 6-Month Treatment Period --
“We believe that navenibart will deliver strong efficacy, low treatment burden, and favorable safety and tolerability and we are thrilled to have initiated our Phase 3 ALPHA-ORBIT trial to support that vision,” said Christopher Morabito, M.D., Chief Medical Officer at Astria Therapeutics. “The Phase 3 program is designed to enable options, providing patients and physicians with the potential to decide what works best for them by administering navenibart only 2 or 4 times per year.”
“We understand from patients that it would be incredibly meaningful to have a therapy that would enable them to live their lives free from the limitations of HAE,” said Dr. Aleena Banerji, Clinical Director MGH Allergy and Immunology Unit, and a Principal Investigator for the ALPHA-ORBIT trial. “Navenibart has demonstrated the potential to prevent HAE attacks with infrequent dosing, which could allow patients the freedom to spend less time managing their disease.”
ALPHA-ORBIT is a global, randomized, double-blind, placebo-controlled Phase 3 pivotal clinical trial to evaluate the efficacy and safety of navenibart over a 6-month treatment period in up to 135 adults and 10 adolescents (open label), with HAE Type 1 or Type 2. Adult patients will be randomized to receive one of three navenibart dose arms: 1) an initial 600 mg dose followed by 300 mg Q3M, 2) 600 mg Q6M, 3) 600 mg Q3M, or placebo; adolescents will receive an initial 600 mg dose followed by 300 mg Q3M. The dose arms support the potential to provide patient-centered dosing flexibility to people with HAE. The primary endpoint is time-normalized monthly HAE attacks at 6 months, and a key secondary endpoint includes the proportion of participants who are attack-free at 6 months. Top-line results from the trial are anticipated in early 2027.
For more information on the ALPHA-ORBIT Phase 3 trial, please visit AlphaOrbit.longboat.com, astriatrials.com, or clinicaltrials.gov, NCT06842823.
After 6 months, patients may be eligible to enter a long-term trial, called ORBIT-EXPANSE, in which all patients will be treated with navenibart and which includes a patient-centered flexible dosing period. The navenibart Phase 3 program consists of the ALPHA-ORBIT Phase 3 trial and ORBIT-EXPANSE long-term trial, which are designed to support registration globally.
The Phase 3 program was designed based on positive final top-line results from target enrollment in the Phase 1b/2 ALPHA-STAR trial of navenibart, which showed rapid onset of robust and durable efficacy, favorable safety and tolerability, and pharmacokinetics and pharmacodynamics consistent with sustained plasma kallikrein inhibition for both Q3M and Q6M administration. Final results included reduction in mean monthly attack rate of 90
About Navenibart:
Navenibart is an investigational monoclonal antibody inhibitor of plasma kallikrein in Phase 3 development for the treatment of HAE. Our goal with navenibart is to provide rapid and sustained HAE attack prevention with a validated mechanism and trusted modality administered every 3 and 6 months. We aim to empower people with HAE to live without limitations from their disease.
About Astria Therapeutics:
Astria Therapeutics is a biopharmaceutical company, and our mission is to bring life-changing therapies to patients and families affected by allergic and immunologic diseases. Our lead program, navenibart (STAR-0215), is a monoclonal antibody inhibitor of plasma kallikrein in clinical development for the treatment of hereditary angioedema. Our second program, STAR-0310, is a monoclonal antibody OX40 antagonist in clinical development for the treatment of atopic dermatitis. Learn more about our company on our website, www.astriatx.com, or follow us on Instagram @AstriaTx and on Facebook and LinkedIn.
Forward Looking Statements:
This press release contains forward-looking statements within the meaning of applicable securities laws and regulations including, but not limited to, statements regarding: our expectations about the potential significance of the topline results from the target enrollment of the Phase 1b/2 ALPHA-STAR clinical trial of navenibart, including with respect to the selection of the dosing for the Phase 3 program; the expected timing of receipt of topline results from the ALPHA-ORBIT trial; the goals of the design of the navenibart Phase 3 program; our goal of developing two dosing options for navenibart and the potential advantages and benefits thereof; the potential for navenibart in the HAE market, including the potential to be the market leading treatment in HAE, the potential therapeutic and other benefits of navenibart as a treatment for HAE, and our vision and goals for the program; and the goal of bringing life changing therapies to patients and families affected by allergic and immunological diseases and to become a leading allergy and immunology company. The use of words such as, but not limited to, “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “goals,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” or "vision," and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Astria’s current beliefs, expectations and assumptions regarding the future of its business, future plans and strategies, future financial performance, results of pre-clinical and clinical results of Astria’s product candidates and other future conditions. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the following risks and uncertainties: changes in applicable laws or regulations; the possibility that we may be adversely affected by other economic, business, and/or competitive factors; risks inherent in pharmaceutical research and development, such as: adverse results in our drug discovery, preclinical and clinical development activities, the risk that the results of preclinical studies, including of navenibart and STAR-0310, may not be replicated in clinical trials, that the preliminary or interim results from clinical trials may not be indicative of the final results, that the results of early stage clinical trials, such as the results from the navenibart Phase 1a clinical trial and the ALPHA-STAR trial, may not be replicated in later stage clinical trials, including the navenibart Phase 3 program; the risk that we may not be able to enroll sufficient patients in our clinical trials on a timely basis, and the risk that any of our clinical trials may not commence, continue or be completed on time, or at all; decisions made by, and feedback received from, the FDA and other regulatory authorities on our regulatory and clinical trial submissions and other feedback from potential clinical trial sites, including investigational review boards at such sites, and other review bodies with respect to navenibart, STAR-0310, and any other future development candidates, and devices for such product candidates; our ability to manufacture sufficient quantities of drug substance and drug product for navenibart, STAR-0310, and any other future product candidates, and devices for such product candidates, on a cost-effective and timely basis, and to develop dosages and formulation for navenibart, STAR-0310, and any other future product candidates that are patient-friendly and competitive; our ability to develop biomarker and other assays, along with the testing protocols therefore; our ability to obtain, maintain and enforce intellectual property rights for navenibart, STAR-0310, and any other future product candidates; our potential dependence on collaboration partners; competition with respect to navenibart, STAR-0310, or any of our other future product candidates; the risk that survey results and market research may not be accurate predictors of the commercial landscape for HAE, the ability of navenibart to compete in HAE, and the anticipated position and attributes of navenibart in HAE based on clinical data to date, its preclinical profile, pharmacokinetic modeling, market research and other data; risks with respect to the ability of STAR-0310 to compete in AD and the anticipated position and attributes of STAR-0310 in atopic dermatitis based on its preclinical profile; our ability to manage our cash usage and the possibility of unexpected cash expenditures; our ability to obtain necessary financing to conduct our planned activities and to manage unplanned cash requirements; the risks and uncertainties related to our ability to recognize the benefits of any additional acquisitions, licenses or similar transactions; and general economic and market conditions; as well as the risks and uncertainties discussed in the “Risk Factors” section of our Annual Report on Form 10-K for the period ended December 31, 2023 and in other filings that we may make with the Securities and Exchange Commission.
New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Astria may not actually achieve the forecasts or expectations disclosed in our forward-looking statements, and investors and potential investors should not place undue reliance on Astria’s forward-looking statements. Neither Astria, nor its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Astria’s views as of any date subsequent to the date hereof.
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Astria Contact:
Investor Relations and Media:
Elizabeth Higgins
investors@astriatx.com
Source: Astria Therapeutics, Inc.
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