Syndax Announces New Data from Secondary Analysis of the Pivotal AGAVE-201 Trial of Niktimvo™ (axatilimab-csfr) in Chronic Graft-Versus-Host Disease to Be Presented at 66th ASH Annual Meeting
Syndax Pharmaceuticals (SNDX) announced new data from secondary analysis of the AGAVE-201 trial for Niktimvo™ (axatilimab-csfr) in chronic graft-versus-host disease to be presented at the ASH Annual Meeting. The pivotal trial met its primary endpoint with a 75% overall response rate at the approved dose of 0.3 mg/kg. More than half of responders showed clinical response by day 56, with an estimated 60% maintaining response at 12 months. Organ-specific responses ranged from 1.2 to 3.7 months, with GI tract, liver, and joints responding faster than lung, mouth, eye, and skin manifestations.
Syndax Pharmaceuticals (SNDX) ha annunciato nuovi dati derivanti dall'analisi secondaria dello studio AGAVE-201 per Niktimvo™ (axatilimab-csfr) nel trattamento della malattia cronica del trapianto contro l'ospite, che saranno presentati al Congresso Annuale ASH. Lo studio chiave ha raggiunto il suo obiettivo primario con un tasso di risposta globale del 75% alla dose approvata di 0,3 mg/kg. Più della metà dei rispondenti ha mostrato una risposta clinica entro il giorno 56, con una stima del 60% che ha mantenuto la risposta dopo 12 mesi. Le risposte specifiche per organo sono variate da 1,2 a 3,7 mesi, con il tratto gastrointestinale, il fegato e le articolazioni che hanno mostrato una risposta più rapida rispetto a polmoni, bocca, occhi e manifestazioni cutanee.
Syndax Pharmaceuticals (SNDX) anunció nuevos datos de un análisis secundario del ensayo AGAVE-201 para Niktimvo™ (axatilimab-csfr) en enfermedad crónica injerto contra huésped, que se presentarán en la Reunión Anual de ASH. El ensayo pivotal alcanzó su objetivo primario con una tasa de respuesta global del 75% a la dosis aprobada de 0,3 mg/kg. Más de la mitad de los respondedores mostraron una respuesta clínica para el día 56, con un 60% estimado manteniendo la respuesta a los 12 meses. Las respuestas específicas por órgano variaron de 1,2 a 3,7 meses, siendo el tracto gastrointestinal, el hígado y las articulaciones los que respondieron más rápidamente que los pulmones, la boca, los ojos y las manifestaciones cutáneas.
신닥스 제약 (SNDX)은 니크팀보™ (액사틸리맙-csfr)의 만성 이식편대숙주병에 대한 AGAVE-201 시험의 2차 분석에서 새로운 데이터를 발표하였으며, 이 데이터는 ASH 연례 회의에서 발표될 예정이다. 주요 임상시험은 승인된 용량 0.3 mg/kg에서 75%의 전체 반응률로 주요 목표를 달성했다. 응답자의 절반 이상이 56일째 임상적 반응을 보였고, 12개월 후에도 60%의 응답자가 반응을 유지할 것으로 추정된다. 장기별 반응 시간은 1.2개월에서 3.7개월 사이로 나타났으며, 위장관, 간 및 관절은 폐, 구강, 눈 및 피부 증상보다 더 빠르게 반응했다.
Syndax Pharmaceuticals (SNDX) a annoncé de nouvelles données provenant de l'analyse secondaire de l'essai AGAVE-201 pour Niktimvo™ (axatilimab-csfr) dans la maladie chronique du greffon contre hôte, qui seront présentées lors de la Réunion Annuelle de l'ASH. L'essai décisif a atteint son objectif principal avec un taux de réponse global de 75 % à la dose approuvée de 0,3 mg/kg. Plus de la moitié des répondants ont montré une réponse clinique au jour 56, avec une estimation de 60 % maintenant la réponse après 12 mois. Les réponses spécifiques aux organes ont varié de 1,2 à 3,7 mois, le tractus gastro-intestinal, le foie et les articulations répondant plus rapidement que les manifestations dans les poumons, la bouche, les yeux et la peau.
Syndax Pharmaceuticals (SNDX) hat neue Daten aus der Sekundäranalyse der AGAVE-201-Studie für Niktimvo™ (axatilimab-csfr) bei chronischer Transplantat-gegen-Wirt-Krankheit angekündigt, die auf dem ASH-Jahrestreffen vorgestellt werden. Die entscheidende Studie erreichte ihren primären Endpunkt mit einer Gesamtansprechrate von 75% bei der genehmigten Dosis von 0,3 mg/kg. Mehr als die Hälfte der Ansprechenden zeigte bis zum Tag 56 eine klinische Antwort, wobei geschätzt wird, dass 60% die Antwort nach 12 Monaten aufrechterhalten. Organspezifische Reaktionen lagen zwischen 1,2 und 3,7 Monaten, wobei der Magen-Darm-Trakt, die Leber und die Gelenke schneller reagierten als die Manifestationen in den Lungen, im Mund, in den Augen und auf der Haut.
- Trial met primary endpoint with 75% overall response rate at approved dose
- 60% of patients maintained response at 12 months
- Rapid response observed with more than half of patients showing improvement by day 56
- Drug demonstrated favorable exposure-efficacy relationship at approved dose
- Slower response rates in lung, mouth, eye, and skin manifestations due to fibrotic nature
- Higher drug exposure increased odds of treatment-emergent adverse events
Insights
The new data from AGAVE-201 trial demonstrates strong efficacy of Niktimvo (axatilimab) in treating chronic GVHD, with
The exposure-response analysis provides important validation for the 0.3 mg/kg biweekly dosing, showing optimal balance between efficacy and safety. Lower exposure increased response odds while higher exposure increased adverse events, scientifically supporting the FDA-approved dosing regimen.
The organ-specific response data reveals important patterns in treatment effectiveness, with faster responses in GI tract and liver (1.2-3.7 months) compared to more fibrotic organs like lungs and skin. This granular understanding of treatment dynamics will help clinicians set appropriate expectations for different patient populations.
– Rapid responses and symptom improvement observed in inflammatory and fibrotic manifestations of chronic GVHD in heavily pretreated patients –
Copies of the abstracts are now available on the ASH website.
"Further analyses of data from the pivotal AGAVE-201 trial continue to reinforce our confidence in Niktimvo's ability to meaningfully advance the chronic GVHD treatment paradigm," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "In collaboration with our partner Incyte, we look forward to providing clinicians and patients with a new approach to treating chronic GVHD and continuing to advance our clinical development programs investigating the potential use of Niktimvo earlier in the treatment of chronic GVHD as well as in other inflammatory and fibrotic diseases including idiopathic pulmonary fibrosis."
The Company will host an in-person investor event, along with a live webcast, to discuss the latest data supporting the Company's pipeline on Monday, December 9, 2024 at 7:00 a.m. PT/ 10:00 a.m. ET during the ASH Annual Meeting. The live webcast will be available on the Investor section of the Company's website at www.syndax.com, where a replay of the event will also be available for a limited time.
Overview of Presentations
AGAVE-201 Secondary Analysis
Incyte and Syndax previously announced positive topline data from the pivotal AGAVE-201 trial of Niktimvo in adult and pediatric patients with refractory chronic GVHD who received at least two prior lines of systemic therapy. The trial met the primary endpoint across all dose cohorts. Among patients who received Niktimvo at the approved dose of 0.3 mg/kg every two weeks (N=79), the overall response rate (ORR) was
The abstract published today highlights new data from the secondary analysis of patients in the 0.3 mg/kg dose cohort which show that more than half of responders had an overall clinical response by day 56 of treatment and more than half of those with at least a seven-point improvement in their modified Lee Symptom Scale (mLSS) score had improvement by day 56 of treatment. In the 0.3 mg/kg dose cohort, the median time to organ-specific responses ranged from 1.2 to 3.7 months across organs. Lower gastrointestinal (GI), upper GI, esophagus, liver, and joints/fascia were typically the fastest organs to respond, whereas lung, mouth, eye, and skin responses were slower due to the highly fibrotic nature of these organ manifestations. Previously reported results from the AGAVE-201 trial showed that Niktimvo was generally well tolerated.
Details for the oral presentation are as follows:
Abstract Number: 98
Title: Dynamics of Overall and Organ-Specific Responses to Axatilimab in Chronic Graft-Versus-Host Disease: Analysis From the AGAVE-201 Study
Presenter: Hannah Choe, M.D.
Session Name: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Predicting and Treating Acute and Chronic GVHD
Session Date: Saturday, December 7, 2024
Session Time: 9:30 AM - 11:00 AM
Presentation Time: 9:45 AM
Pooled Exposure-Response Analysis
The abstract published today describes the exposure-efficacy and exposure-safety relationships in patients with chronic GVHD treated with distinct doses of axatilimab in the pivotal Phase 2 AGAVE-201 trial and the prior Phase 1/2 trial. For the exposure-efficacy analysis (n=239), ORR and mLSS responses were associated with axatilimab exposure, with lower axatilimab exposure increasing the odds of response. For the exposure-safety analysis (n=278), all safety endpoints except infections of unspecified etiology were associated with axatilimab exposure, with higher axatilimab exposure increasing the odds of treatment-emergent adverse events. These results provide rationale for the 0.3 mg/kg every two weeks regimen, which is the FDA approved dose of axatilimab (Niktimvo).
Details for the poster presentation are as follows:
Abstract Number: 2140
Title: Exposure-Response Relationships for Axatilimab, a Humanized Monoclonal Antibody Targeting CSF-1R, in Patients With Chronic Graft-Versus-Host Disease
Presenter: Yan-ou Yang, Ph.D.
Session Name: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Poster I
Session Date: Saturday, December 7, 2024
Presentation Time: 5:30 PM - 7:30 PM
Preclinical Mechanism of Action Data
Preclinical data detailing the anti-inflammatory and anti-fibrotic mechanism through which axatilimab is thought to impact the disease process in chronic GVHD will be presented.
Details for the poster presentation are as follows:
Abstract Number: 1147
Title: Axatilimab Abrogates Inflammatory Cytokines and Chemokines and Interrupts the Differentiation of Monocytes to Macrophages, a Pathogenic Driver of Inflammation and Fibrosis in cGVHD
Presenter: Anamika Bajpai, Ph.D.
Session Name: 201. Granulocytes, Monocytes, and Macrophages: Poster I
Session Date: Saturday, December 7, 2024
Presentation Time: 5:30 PM - 7:30 PM
About AGAVE-201
The global AGAVE-201 dose-ranging trial evaluated the efficacy, safety, and tolerability of axatilimab in 241 adult and pediatric patients with recurrent or refractory active chronic GVHD whose disease had progressed after two or more prior therapies. Patients were randomized to one of three treatment groups that investigated a distinct dose of axatilimab administered at 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks or 3.0 mg/kg every four weeks. The trial's primary endpoint was the proportion of patients in each dose group who achieved an objective response as defined by 2014 NIH Consensus Criteria for chronic GVHD by cycle 7 day 1. Secondary endpoints included duration of response, percent reduction in daily steroid dose, organ specific response rates and validated quality-of-life assessments using the Modified Lee Symptom Scale.
For more information about AGAVE-201, visit https://www.clinicaltrials.gov/study/NCT04710576.
About Niktimvo™ (axatilimab-csfr)
Niktimvo (axatilimab-csfr) is a first-in-class anti-CSF-1R antibody approved for use in the
In the
In 2016, Syndax licensed exclusive worldwide rights to develop and commercialize axatilimab from UCB. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab in chronic GVHD and any future indications.
Axatilimab is being studied in frontline combination trials in chronic GVHD – a Phase 2 combination trial with ruxolitinib (NCT06388564) is underway and a Phase 3 combination trial with steroids is in preparation. Axatilimab is also being studied in an ongoing Phase 2 trial in patients with idiopathic pulmonary fibrosis (NCT06132256).
Niktimvo is a trademark of Incyte.
All other trademarks are the property of their respective owners.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Niktimvo™ (axatilimab-csfr) can cause infusion-related reactions. Infusion-related reactions, including hypersensitivity reactions, occurred in
Premedicate with an antihistamine and an antipyretic for patients who have previously experienced an infusion-related reaction to Niktimvo. Monitor patients for signs and symptoms of infusion-related reactions, including fever, chills, rash, flushing, dyspnea, and hypertension. Interrupt or slow the rate of infusion or permanently discontinue Niktimvo based on severity of the reaction.
Embryo-Fetal Toxicity
Based on its mechanism of action, Niktimvo may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with Niktimvo and for 30 days after the last dose.
ADVERSE REACTIONS
Serious adverse reactions occurred in
The most common (≥
Clinically relevant adverse reactions in <
- Eye disorders: periorbital edema
- Skin and subcutaneous skin disorders: pruritus
- Vascular disorders: hypertension
Immunogenicity: Anti-Drug Antibody–Associated Adverse Reactions
Across treatment arms in patients with cGVHD who received Niktimvo in clinical trials, among the patients who developed anti-drug antibodies (ADAs), hypersensitivity reactions occurred in
USE IN SPECIFIC POPULATIONS
Lactation
Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 30 days after the last dose of Niktimvo.
Females and Males of Reproductive Potential
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating Niktimvo.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with Niktimvo and for 30 days after the last dose of Niktimvo.
DOSAGE AND ADMINISTRATION
Dosage Modifications for Adverse Reactions
Monitor aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine phosphokinase (CPK), amylase, and lipase prior to the start of Niktimvo therapy, every 2 weeks for the first month, and every 1 to 2 months thereafter until abnormalities are resolved. See Table 1 in the Prescribing Information for more recommendations.
Please see the full Prescribing Information for Niktimvo.
About Syndax
Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a selective menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. For more information, please visit www.syndax.com/ or follow the Company on X (formerly Twitter) and LinkedIn.
Syndax Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," "intend," "believe" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials, the reporting of clinical data for Syndax's product candidates, the acceptance of Syndax and its partners' products in the marketplace, sales, marketing, manufacturing and distribution requirements, and the potential use of our product candidates to treat various cancer indications and fibrotic diseases. Many factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; failure of Syndax's collaborators to support or advance collaborations or product candidates; and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the
Syndax Contact:
Sharon Klahre
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
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FAQ
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