Once-Weekly Apraglutide Showed Consistent Treatment Effect Across Baseline Demographics and Disease Characteristics in Adults with Short Bowel Syndrome with Intestinal Failure (SBS-IF), According to New STARS Phase III Data from Ironwood at ACG 2024
Ironwood Pharmaceuticals presented new findings from the STARS Phase III trial of apraglutide at ACG 2024, showing consistent treatment effects across patient subgroups with Short Bowel Syndrome with Intestinal Failure (SBS-IF). The trial met its primary endpoint with a -25.5% vs -12.5% (p=0.001) relative change in weekly parenteral support volume at week 24 vs. placebo.
The analyses demonstrated consistent efficacy across demographics including gender, age, body weight, region, and SBS characteristics. Safety data showed high treatment compliance (>98%) with low incidence of adverse events. Ironwood expects to complete U.S. regulatory submission in Q1 2025.
Ironwood Pharmaceuticals ha presentato nuovi risultati dallo studio STARS Fase III su apraglutide durante l'ACG 2024, mostrando effetti terapeutici coerenti tra i sottogruppi di pazienti con Sindrome dell'Intestino Corto con Insufficienza Intestinale (SBS-IF). Lo studio ha raggiunto il suo obiettivo primario con una variazione relativa del volume di supporto parenterale settimanale del -25.5% rispetto al -12.5% (p=0.001) alla settimana 24 rispetto al placebo.
Le analisi hanno dimostrato un'efficacia coerente attraverso le variabili demografiche, inclusi genere, età, peso corporeo, regione e caratteristiche della SBS. I dati sulla sicurezza hanno mostrato un'elevata compliance al trattamento (>98%) con una bassa incidenza di eventi avversi. Ironwood prevede di completare la presentazione normativa negli Stati Uniti nel primo trimestre del 2025.
Ironwood Pharmaceuticals presentó nuevos hallazgos del ensayo STARS Fase III sobre apraglutide en el ACG 2024, mostrando efectos de tratamiento consistentes en subgrupos de pacientes con Síndrome de Intestino Corto con Insuficiencia Intestinal (SBS-IF). El ensayo cumplió con su objetivo primario con un cambio relativo en el volumen de soporte parenteral semanal de -25.5% frente a -12.5% (p=0.001) a las 24 semanas en comparación con placebo.
Las análisis demostraron eficacia consistente a través de variables demográficas como género, edad, peso corporal, región y características de SBS. Los datos de seguridad mostraron una alta adherencia al tratamiento (>98%) con una baja incidencia de eventos adversos. Ironwood espera completar la presentación regulatoria en EE. UU. en el primer trimestre de 2025.
아이언우드 제약은 ACG 2024에서 아프라글루타이드의 STARS 3상 시험에서 새로운 발견을 발표하며, 장 부족 증후군 및 장 기능 부전(SBS-IF) 환자의 하위 그룹 간에 일관된 치료 효과를 보여주었습니다. 이 시험은 주 24에서 위약 대비 주간 비경구적 지원량의 상대적 변화가 -25.5% 대 -12.5%(p=0.001)로 주요 목표를 달성했습니다.
분석 결과는 성별, 연령, 체중, 지역, SBS 특성을 포함한 인구 통계에서 일관된 효능을 보여주었습니다. 안전성 데이터는 높은 치료 준수율(>98%)과 낮은 부작용 발생률을 나타냈습니다. 아이언우드는 2025년 1분기에 미국 규제 제출을 완료할 것으로 예상합니다.
Ironwood Pharmaceuticals a présenté de nouvelles découvertes issues de l'essai STARS Phase III concernant apraglutide lors de l'ACG 2024, montrant des effets de traitement cohérents entre les sous-groupes de patients atteints de syndrome de l'intestin court avec insuffisance intestinale (SBS-IF). L'essai a atteint son objectif principal avec un changement relatif du volume de soutien par enteral hebdomadaire de -25,5 % contre -12,5 % (p=0,001) à la semaine 24 par rapport au placebo.
Les analyses ont démontré une efficacité cohérente à travers les caractéristiques démographiques, y compris le sexe, l'âge, le poids corporel, la région et les caractéristiques du SBS. Les données de sécurité ont montré un taux de conformité élevé au traitement (>98%) avec une faible incidence d'événements adverses. Ironwood prévoit de compléter la soumission réglementaire aux États-Unis au premier trimestre de 2025.
Ironwood Pharmaceuticals präsentierte neue Ergebnisse aus der STARS Phase-III-Studie zu apraglutide auf der ACG 2024 und zeigte konsistente Behandlungseffekte bei Patientensubgruppen mit Kurzdarmsyndrom und intestinaler Insuffizienz (SBS-IF). Die Studie erreichte ihren primären Endpunkt mit einer relativen Veränderung des wöchentlichen parenteralen Unterstützungsvolumens von -25,5 % gegenüber -12,5 % (p=0,001) in Woche 24 im Vergleich zur Placebo-Gruppe.
Die Analysen zeigten eine konsistente Wirksamkeit über demografische Merkmale hinweg, einschließlich Geschlecht, Alter, Körpergewicht, Region und SBS-Eigenschaften. Die Sicherheitsdaten wiesen auf eine hohe Therapietreue (>98%) mit einer niedrigen Inzidenz von Nebenwirkungen hin. Ironwood erwartet, die behördliche Einreichung in den USA im ersten Quartal 2025 abzuschließen.
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– New safety and tolerability data show high treatment compliance with apraglutide, low incidence of injection site reactions and adverse events associated with GI tolerability –
– Findings reinforce the clinical profile of once-weekly apraglutide; Ironwood expects to complete
– One apraglutide poster recognized as presidential poster recipient –
– New linaclotide data shed light on treatment outcomes across patient demographics –
SBS-IF, a rare chronic debilitating malabsorptive condition in which patients are dependent on parenteral support (PS), affects an estimated 18,000 adult patients in the
STARS represents the largest Phase III trial in SBS-IF conducted to date, and the only study that pre-specified patient stratification based on remnant bowel anatomy. Ironwood previously reported that the STARS clinical trial met its primary endpoint of relative change from baseline in actual weekly PS volume at week 24 vs. placebo (-
“SBS-IF is a rare condition, but it is extremely variable in terms of patient demographics and the way in which they present,” said Kishore R Iyer, MBBS, FRCS (Eng), FACS, Director of Adult and Pediatric Intestine Rehabilitation & Transplantation at The Mount Sinai Hospital in
Topline results from STARS were previously announced in February 2024, and the topline data was also presented at Digestive Disease Week® (DDW) in May.
In addition to the STARS Phase III oral presentation, Ironwood and its collaborators presented new safety findings from the STARS study, with this abstract receiving a Presidential Poster Award.
“As we work to make apraglutide available as potentially the first once-weekly treatment option for patients with SBS who are dependent on PS, we are focused on continuing to educate the SBS community on the potential of this compound across profiles of adult patients given the known patient heterogeneity,” said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals. “Patient demographic analyses play a key role in understanding the impact of any medication, and our focus on these analyses extends to all our data at ACG this year.”
In addition to the apraglutide data, Ironwood is also featuring linaclotide data at ACG.
More details on these data are provided below.
Safety Data from STARS
“Safety and Tolerability of Once-Weekly Glucagon-like Peptide-2 Analog Apraglutide in Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF): Results from a Global, Phase 3, Randomized, Double-Blind Trial” (poster number 1521, Presidential Poster Award) was presented by Mena Boules, M.D., Ironwood Pharmaceuticals. This analysis showed that apraglutide had a safety profile consistent with previous apraglutide studies, with no new safety concerns. Incidence of AEs, serious AEs and AEs of Grade ≥ 3 was similar between treatment arms. Dose interruptions due to AEs were also similar between apraglutide and placebo (
Linaclotide Treatment Outcomes by Patient Demographic
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“Efficacy, Safety and Time to Response of Linaclotide in Adult Patients With Chronic Idiopathic Constipation: A Post Hoc Subgroup Analysis by Age” (poster number P0615) was presented by Lin Chang, M.D., Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, UCLA,
Los Angeles . The results showed that linaclotide-treated patients with CIC tended to show greater and faster improvement in bowel and abdominal symptoms compared with placebo and had similar safety profiles across age groups (< 65 and ≥ 65 yrs) for both linaclotide doses (72 mcg or 145 mcg). The authors noted that the small sample size for patients aged ≥ 65 years should be considered when interpreting these data.
Two studies will be presented by Baha Moshiree, M.D., Division of Gastroenterology, Advocate Health Wake Forest Medical University, Charlotte.
- “Efficacy and Safety of Linaclotide in Patients With Chronic Idiopathic Constipation: A Post Hoc Analysis of Phase 3 Clinical Study Data Assessing Primary and Additional Endpoints by Race and Ethnicity, and by Age” (poster number P2334). The study showed that linaclotide improved complete spontaneous bowel movement (CSBM) responder rates and CIC symptoms, and had a similar safety profile, across most races/ethnicities and ages in CIC patients. The authors note that small sample sizes for Asian and other patient groups (and some age subgroups) limit data interpretation and highlight the need to recruit more diverse populations in clinical studies.
- “Impact of Weight on the Efficacy, Time to Response and Safety of Linaclotide in Adults With Chronic Idiopathic Constipation or Irritable Bowel Syndrome With Constipation: Post Hoc Descriptive Analysis by Body Mass Index” (poster number P4073). The study showed that linaclotide improved bowel symptoms in patients with CIC and IBS-C and was similarly efficacious in those with normal weight, overweight or obesity. Treatment-emergent adverse events (TEAEs) were consistent with the known safety profile of linaclotide.
About STARS
The STARS (STudy of ApRaglutide in SBS) pivotal Phase III trial represents the largest Phase III trial in SBS-IF to date.
This global, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of weekly subcutaneous injections of apraglutide in adult patients with SBS-IF. STARS randomized 164 patients 2:1 and 163 were dosed to receive either once-weekly apraglutide or placebo. Patients were stratified approximately 50/50 by remnant bowel anatomy (stoma vs. colon-in continuity) and evaluated over 24 weeks (stoma and colon-in-continuity subpopulations) and 48 weeks (colon-in-continuity subpopulation only). The primary endpoint was relative change from baseline in actual weekly PS volume at week 24. Key secondary endpoints included patients who achieved a reduction from baseline of at least 1 day/week off PS at week 24 (overall population); relative change from baseline in actual weekly PS volume at week 24 (stoma subpopulation); patients who achieved a reduction from baseline of at least 1 day/week off PS at week 48 (colon-in-continuity subpopulation); and patients reaching enteral autonomy at week 48 (colon-in-continuity subpopulation).
The study was conducted in 18 countries with enrollment from 68 study sites.
About Short Bowel Syndrome
SBS is a serious and chronic condition where there is diminished absorptive capacity for fluids and/or nutrients, sometimes requiring dependence on parenteral support to maintain health. Short bowel syndrome typically occurs because of extensive intestinal resection, and patients with SBS who are dependent on parenteral support, also referred to as SBS with intestinal failure (SBS-IF), often experience significant quality of life impact and are at risk of severe complications such as infection. An estimated 18,000 adult patients suffer from SBS-IF in the
About Apraglutide
Apraglutide is an investigational, next-generation, long-acting synthetic GLP-2 analog being developed for a range of rare gastrointestinal diseases where GLP-2 can play a central role in addressing disease pathophysiology, including short bowel syndrome with intestinal failure (SBS-IF) and Acute Graft-Versus-Host Disease (aGVHD).
About LINZESS (Linaclotide)
LINZESS® is the #1 prescribed brand in the
LINZESS is not a laxative; it is the first medicine approved by the FDA in a class called GC-C agonists. LINZESS contains a peptide called linaclotide that activates the GC-C receptor in the intestine. Activation of GC-C is thought to result in increased intestinal fluid secretion and accelerated transit and a decrease in the activity of pain-sensing nerves in the intestine. The clinical relevance of the effect on pain fibers, which is based on nonclinical studies, has not been established.
In
LINZESS Important Safety Information
INDICATIONS AND USAGE
LINZESS® (linaclotide) is indicated for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults and functional constipation (FC) in children and adolescents 6 to 17 years of age. It is not known if LINZESS is safe and effective in children with FC less than 6 years of age or in children with IBS-C less than 18 years of age.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE
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LINZESS is contraindicated in patients less than 2 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. |
Contraindications
- LINZESS is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.
- LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
- LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated guanylate cyclase (GC-C) agonism, which was associated with increased mortality within the first 24 hours due to dehydration. There was no age dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients.
Diarrhea
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In adults, diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in
2% of 145 mcg and 290 mcg LINZESS-treated patients and in <1% of 72 mcg LINZESS-treated CIC patients. -
In children and adolescents 6 to 17 years of age, diarrhea was the most common adverse reaction in 72 mcg LINZESS-treated patients in the FC double-blind placebo-controlled trial. Severe diarrhea was reported in <
1% of 72 mcg LINZESS treated patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.
Common Adverse Reactions (incidence ≥
- In IBS-C or CIC adult patients: diarrhea, abdominal pain, flatulence, and abdominal distension.
- In FC pediatric patients: diarrhea.
Please see full Prescribing Information including Boxed Warning:
https://www.rxabbvie.com/pdf/linzess_pi.pdf
LINZESS® and CONSTELLA® are registered trademarks of Ironwood Pharmaceuticals, Inc. Any other trademarks referred to in this press release are the property of their respective owners. All rights reserved.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (Nasdaq: IRWD), an S&P SmallCap 600® company, is a leading gastrointestinal (GI) healthcare company on a mission to advance the treatment of GI diseases and redefine the standard of care for GI patients. We are pioneers in the development of LINZESS® (linaclotide), the
Founded in 1998, Ironwood Pharmaceuticals is headquartered in
We routinely post information that may be important to investors on our website, www.ironwoodpharma.com. In addition, you can follow us on X and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about the assessment of the data from the Phase III STARS clinical trial of apraglutide; the efficacy, safety and tolerability of apraglutide; Ironwood’s plan to submit an NDA and marketing applications to other regulatory filings for apraglutide and the expected timing to complete
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Media:
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Source: Ironwood Pharmaceuticals, Inc.
FAQ
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