Ironwood Pharmaceuticals Provides Clinical and Regulatory Update on Apraglutide
Ironwood Pharmaceuticals (IRWD) announced that the FDA requires a confirmatory Phase 3 trial for apraglutide, their treatment for short bowel syndrome with intestinal failure (SBS-IF). This requirement emerged after pharmacokinetic analysis revealed that the exposure and dose delivered in the STARS Phase 3 trial were lower than planned due to preparation and administration issues.
Despite strong safety and efficacy data from the STARS Phase 3 trial, which was the largest SBS-IF trial to date, and positive results showing 27 patients achieving enteral autonomy in the long-term extension trial, the FDA's feedback indicates additional clinical validation is necessary. The company plans to work with the FDA on designing the confirmatory trial while continuing the long-term extension study.
In response to this development, Ironwood has engaged Goldman Sachs to explore strategic alternatives to maximize stockholder value while continuing to advance apraglutide's development.
Ironwood Pharmaceuticals (IRWD) ha annunciato che la FDA richiede uno studio di conferma di Fase 3 per apraglutide, il loro trattamento per la sindrome dell'intestino corto con insufficienza intestinale (SBS-IF). Questa richiesta è emersa dopo che l'analisi farmacocinetica ha rivelato che l'esposizione e la dose somministrata nello studio di Fase 3 STARS erano inferiori a quelle pianificate a causa di problemi di preparazione e somministrazione.
Nonostante dati di sicurezza ed efficacia solidi provenienti dallo studio di Fase 3 STARS, che è stato il più grande studio su SBS-IF fino ad oggi, e risultati positivi che mostrano 27 pazienti che hanno raggiunto l'autonomia enterale nello studio di estensione a lungo termine, il feedback della FDA indica che è necessaria una ulteriore validazione clinica. L'azienda prevede di collaborare con la FDA per progettare lo studio di conferma continuando allo stesso tempo lo studio di estensione a lungo termine.
In risposta a questo sviluppo, Ironwood ha coinvolto Goldman Sachs per esplorare alternative strategiche al fine di massimizzare il valore per gli azionisti mentre continua a far progredire lo sviluppo di apraglutide.
Ironwood Pharmaceuticals (IRWD) anunció que la FDA requiere un ensayo de confirmación de Fase 3 para apraglutida, su tratamiento para el síndrome de intestino corto con insuficiencia intestinal (SBS-IF). Este requisito surgió después de que el análisis farmacocinético revelara que la exposición y la dosis administrada en el ensayo de Fase 3 STARS fueron inferiores a lo planeado debido a problemas de preparación y administración.
A pesar de datan de seguridad y eficacia sólidos del ensayo de Fase 3 STARS, que ha sido el mayor ensayo de SBS-IF hasta la fecha, y de los resultados positivos que muestran que 27 pacientes lograron autonomía enteral en el ensayo de extensión a largo plazo, el feedback de la FDA indica que se necesita una validación clínica adicional. La empresa planea trabajar con la FDA en el diseño del ensayo de confirmación mientras continúa con el estudio de extensión a largo plazo.
En respuesta a este desarrollo, Ironwood ha involucrado a Goldman Sachs para explorar alternativas estratégicas que maximicen el valor para los accionistas mientras continúa avanzando en el desarrollo de apraglutida.
아이언우드 제약 (IRWD)는 FDA가 단장증후군과 장기능부전(SBS-IF) 치료제인 아프라글루타이드에 대해 확인 임상 3상 시험을 요구한다고 발표했습니다. 이 요구는 약물의 약리학적 분석 결과 STARS 3상 시험에서 노출량과 투여량이 준비 및 투여 문제로 인해 계획보다 낮았다는 사실이 드러나면서 나타났습니다.
STARS 3상 시험에서 강력한 안전성 및 효능 데이터가 나왔음에도 불구하고, 이는 지금까지의 SBS-IF 시험 중 가장 큰 규모였으며, 장기 연장 시험에서 27명의 환자가 장내 자율성을 달성한 긍정적인 결과가 나왔음에도 불구하고, FDA의 피드백은 추가적인 임상 검증이 필요하다고 밝혔습니다. 회사는 확인 시험을 설계하는 데 FDA와 협력할 계획이며, 동시에 장기 연장 연구를 계속 진행할 것입니다.
이 개발에 대한 대응으로, 아이언우드는 골드만 삭스를 참여시켜 주주 가치를 극대화하기 위한 전략적 대안을 모색하고 있으며, 아프라글루타이드의 개발을 계속 진행하고 있습니다.
Ironwood Pharmaceuticals (IRWD) a annoncé que la FDA exige un essai de confirmation de Phase 3 pour l'apraglutide, leur traitement pour le syndrome de l'intestin court avec insuffisance intestinale (SBS-IF). Cette exigence est apparue après qu'une analyse pharmacocinétique a révélé que l'exposition et la dose administrée dans l'essai de Phase 3 STARS étaient inférieures à celles prévues en raison de problèmes de préparation et d'administration.
Malgré des données de sécurité et d'efficacité solides provenant de l'essai de Phase 3 STARS, qui était le plus grand essai SBS-IF à ce jour, et des résultats positifs montrant que 27 patients ont atteint l'autonomie entérale dans l'essai d'extension à long terme, le retour de la FDA indique qu'une validation clinique supplémentaire est nécessaire. L'entreprise prévoit de travailler avec la FDA sur la conception de l'essai de confirmation tout en poursuivant l'étude d'extension à long terme.
En réponse à ce développement, Ironwood a engagé Goldman Sachs pour explorer des alternatives stratégiques afin de maximiser la valeur pour les actionnaires tout en continuant à faire progresser le développement de l'apraglutide.
Ironwood Pharmaceuticals (IRWD) hat angekündigt, dass die FDA eine bestätigende Phase-3-Studie für Apraglutid, ihre Behandlung für das Kurzschlussdarmsyndrom mit intestinaler Insuffizienz (SBS-IF), verlangt. Diese Anforderung ergab sich, nachdem eine pharmakokinetische Analyse gezeigt hatte, dass die Exposition und die Dosis, die in der STARS-Phase-3-Studie verabreicht wurden, aufgrund von Vorbereitungs- und Verabreichungsproblemen geringer waren als geplant.
Trotz starker Sicherheits- und Wirksamkeitsdaten aus der STARS-Phase-3-Studie, die die größte SBS-IF-Studie bis heute war, und positiver Ergebnisse, die zeigen, dass 27 Patienten in der Langzeitverlängerungsstudie enterale Autonomie erreicht haben, deutet das Feedback der FDA darauf hin, dass eine zusätzliche klinische Validierung erforderlich ist. Das Unternehmen plant, mit der FDA an der Gestaltung der bestätigenden Studie zu arbeiten, während es gleichzeitig die Langzeitverlängerungsstudie fortsetzt.
Als Reaktion auf diese Entwicklung hat Ironwood Goldman Sachs beauftragt, strategische Alternativen zu erkunden, um den Wert für die Aktionäre zu maximieren, während die Entwicklung von Apraglutid weiter vorangetrieben wird.
- Strong safety and efficacy data from STARS Phase 3 trial, the largest SBS-IF trial to date
- 27 patients achieved enteral autonomy in long-term extension trial
- Apraglutide maintains potential to be a blockbuster drug
- FDA requires additional Phase 3 trial, delaying potential market approval
- STARS trial had dose preparation and administration issues leading to lower than planned drug exposure
- Additional trial requirement will increase development costs and time to market
Insights
Ironwood Pharmaceuticals has received a significant regulatory setback for apraglutide, its GLP-2 analog being developed for Short Bowel Syndrome with Intestinal Failure (SBS-IF). The FDA has determined that a confirmatory Phase 3 trial will be necessary before seeking approval, despite positive results from the STARS trial.
The core issue centers on a pharmacokinetic analysis revealing that the exposure and dose delivered in the STARS trial were lower than planned due to preparation and administration problems. This technical issue has effectively invalidated what would have been the pivotal trial for approval submission.
This represents a major delay in Ironwood's regulatory timeline, likely extending the path to potential approval by 2-3 years minimum given the time required to design, recruit, conduct, and analyze a new Phase 3 study in this rare disease population.
The engagement of Goldman Sachs to explore "strategic alternatives" signals the company is considering fundamental options such as a potential sale, merger, or significant restructuring in light of this setback. With a market cap of just
The continued emphasis on positive data from the STARS trial (27 patients achieving enteral autonomy) suggests Ironwood will attempt to leverage these findings in designing the confirmatory trial, potentially helping to streamline requirements while addressing the FDA's concerns regarding proper dosing.
This regulatory setback creates a significant capital allocation dilemma for Ironwood. The requirement for a new confirmatory Phase 3 trial introduces substantial cash burn considerations that will strain the company's resources and extend the timeline to potential commercialization by years.
The decision to engage Goldman Sachs is particularly telling - management recognizes that financing another costly Phase 3 program may not be the optimal path forward for shareholders. With the stock trading near
- Outright sale to a larger pharmaceutical company with established GI franchise
- Partnership deals to share development costs for apraglutide
- Restructuring to reduce operational expenses while pursuing the new trial
Ironwood's assertion that apraglutide still has "blockbuster" potential is notable but must be evaluated against the extended timeline. The dose preparation and administration issues in the original trial represent a significant technical oversight that has now created material consequences for the approval pathway.
The silver lining is the continued positive efficacy signals from the STARS data, particularly the 27 patients achieving enteral autonomy. This suggests the drug's mechanism remains valid despite the dosing issues, and maintains the asset's fundamental value proposition for SBS-IF patients who currently have treatment options.
For investors, this news fundamentally reframes the risk/reward equation, pushing potential approval and revenue generation significantly further into the future while raising questions about Ironwood's financial capacity to independently complete the development journey.
– Feedback from recent FDA interaction indicates that a confirmatory Phase 3 trial evaluating apraglutide in SBS-IF is needed to seek approval –
– Company has engaged Goldman Sachs & Co. LLC to explore strategic alternatives –
Apraglutide is a once weekly, long-acting synthetic GLP-2 analog with the potential to treat a range of rare gastrointestinal diseases where GLP-2 can play a central role in addressing disease pathophysiology, and it is the only GLP-2 analog to achieve a statistically significant reduction in weekly parenteral support volume with once-weekly dosing in patients with SBS.
In preparation for the new drug application (NDA) submission, pharmacokinetic analysis indicated that the exposure and dose delivered in the STARS Phase 3 trial were lower than planned due to dose preparation and administration. Based on the strength of the STARS Phase 3 results, Ironwood believed that there was a regulatory path forward. However, following recent dialogue with the FDA it became clear that a confirmatory Phase 3 trial is needed to seek approval. Ironwood plans to work with the FDA on the design of a confirmatory Phase 3 trial and the regulatory path forward.
Apraglutide generated strong safety and efficacy data in the STARS Phase 3 trial, the largest SBS-IF trial to date, and, following an analysis of long-term extension trial data, 27 apraglutide-dosed patients dependent on parenteral support achieved enteral autonomy, which is the ultimate goal for these patients. Consistent with FDA discussions, Ironwood plans to continue the long-term extension trial and believes the data from the STARS trial will continue to be an integral part of an NDA submission package.
“We are disappointed in this outcome, as we firmly believe apraglutide has the potential to provide tremendous value to patients with SBS-IF who suffer from increased mortality, and reduced quality of life, and will now have to wait for the results of a confirmatory Phase 3 trial,” said Tom McCourt, chief executive officer of Ironwood. “We are focused on the best path forward to get apraglutide to market, which we believe still has the potential to be a blockbuster drug. Concurrently, we will be exploring strategic alternatives for the company in an effort to maximize stockholder value. We are grateful to the patients, families, and clinicians who have and continue to support our clinical development programs.”
About Short Bowel Syndrome (SBS)
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 chronically 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 Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (Nasdaq: IRWD) is a biotechnology company developing and commercializing life-changing therapies for people living with gastrointestinal (GI) and rare diseases. Ironwood is advancing apraglutide, a next-generation, long-acting synthetic GLP-2 analog being developed for short bowel syndrome patients who are dependent on parenteral support. In addition, Ironwood has been a pioneer 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 at www.ironwoodpharma.com. In addition, follow us on X and on 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 Ironwood’s ability to execute on its mission; Ironwood’s strategy, business, financial position and operations; that a confirmatory Phase 3 trial is needed to seek approval of apraglutide in SBS-IF who are dependent on parenteral support; the belief that the data from the STARS Phase 3 trial will continue to be an integral part of an NDA submission package; Ironwood’s engagement with Goldman Sachs to explore strategic alternatives for the company to maximize value for stockholders; Ironwood’s plan to continue the long-term extension study and work with the FDA on the design of a confirmatory Phase 3 trial and the regulatory path forward; the belief that apraglutide has the potential to be a blockbuster drug. These forward-looking statements speak only as of the date of this press release, and Ironwood undertakes no obligation to update these forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include those related to the effectiveness of development and commercialization efforts by us and our partners; preclinical and clinical development, manufacturing and formulation development of linaclotide, apraglutide, IW-3300, and our other product candidates; the risk of uncertainty relating to pricing and reimbursement policies in the
View source version on businesswire.com: https://www.businesswire.com/news/home/20250414687154/en/
Company contact:
Greg Martini
gmartini@ironwoodpharma.com
Investors:
Precision AQ (formerly Stern Investor Relations)
Stephanie Ascher
Stephanie.Ascher@precisionaq.com
Source: Ironwood Pharmaceuticals, Inc.
FAQ
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