Pliant Therapeutics Provides Update on BEACON-IPF, a Phase 2b/3 Trial in Patients with Idiopathic Pulmonary Fibrosis
Pliant Therapeutics (PLRX) has discontinued its BEACON-IPF Phase 2b trial of bexotegrast in idiopathic pulmonary fibrosis (IPF) patients following safety concerns, despite showing early efficacy signs in forced vital capacity (FVC). The discontinuation came after reviews by the trial's Data Safety Monitoring Board and an external expert panel.
The trial, with approximately 17 weeks mean exposure duration, showed comparable IPF-related adverse events (around 10%) in both dose groups. However, an imbalance was noted due to unusually low adverse event rates (<3%) in the placebo group. This contrasts with the Phase 2a INTEGRIS-IPF trial, where adverse events were similar between bexotegrast-treated (7%) and placebo groups (10%).
The company plans to analyze the complete data and consider additional Phase 2b studies with lower doses for pulmonary fibrosis and other non-respiratory indications. Meanwhile, Pliant continues developing other assets, including PLN-101095 in oncology, currently in Phase 1 trials.
Pliant Therapeutics (PLRX) ha interrotto il suo studio BEACON-IPF di fase 2b su bexotegrast in pazienti con fibrosi polmonare idiopatica (IPF) a causa di preoccupazioni per la sicurezza, nonostante segni iniziali di efficacia nella capacità vitale forzata (FVC). L'interruzione è avvenuta dopo le revisioni del Comitato di Monitoraggio della Sicurezza dei Dati dello studio e di un panel di esperti esterni.
Lo studio, con una durata media di esposizione di circa 17 settimane, ha mostrato eventi avversi correlati all'IPF comparabili (circa 10%) in entrambi i gruppi di dose. Tuttavia, è stata notata una discrepanza a causa di tassi di eventi avversi insolitamente bassi (<3%) nel gruppo placebo. Questo contrasta con lo studio di fase 2a INTEGRIS-IPF, dove gli eventi avversi erano simili tra i gruppi trattati con bexotegrast (7%) e placebo (10%).
L'azienda prevede di analizzare i dati completi e considerare ulteriori studi di fase 2b con dosi inferiori per la fibrosi polmonare e altre indicazioni non respiratorie. Nel frattempo, Pliant continua a sviluppare altri asset, incluso PLN-101095 in oncologia, attualmente in studi di fase 1.
Pliant Therapeutics (PLRX) ha discontinuado su ensayo BEACON-IPF de fase 2b de bexotegrast en pacientes con fibrosis pulmonar idiopática (IPF) debido a preocupaciones de seguridad, a pesar de mostrar signos tempranos de eficacia en la capacidad vital forzada (FVC). La discontinuación se produjo tras las revisiones del Comité de Monitoreo de Seguridad de Datos del ensayo y de un panel de expertos externos.
El ensayo, con una duración media de exposición de aproximadamente 17 semanas, mostró eventos adversos relacionados con la IPF comparables (alrededor del 10%) en ambos grupos de dosis. Sin embargo, se notó un desequilibrio debido a tasas de eventos adversos inusualmente bajas (<3%) en el grupo placebo. Esto contrasta con el ensayo de fase 2a INTEGRIS-IPF, donde los eventos adversos fueron similares entre los grupos tratados con bexotegrast (7%) y placebo (10%).
La empresa planea analizar los datos completos y considerar estudios adicionales de fase 2b con dosis más bajas para la fibrosis pulmonar y otras indicaciones no respiratorias. Mientras tanto, Pliant continúa desarrollando otros activos, incluyendo PLN-101095 en oncología, actualmente en ensayos de fase 1.
Pliant Therapeutics (PLRX)는 안전성 우려로 인해 특발성 폐섬유증 (IPF) 환자에서 bexotegrast에 대한 BEACON-IPF 2b 임상을 중단했습니다. 이는 강제 폐활량 (FVC)에서 초기 효능 신호를 보였음에도 불구하고 이루어진 결정입니다. 중단은 임상시험의 데이터 안전 모니터링 위원회와 외부 전문가 패널의 검토 후에 이루어졌습니다.
약 17주 동안의 평균 노출 기간을 가진 이 시험은 두 용량 그룹 모두에서 IPF 관련 부작용이 비슷하게 나타났습니다 (약 10%). 그러나 위약 그룹에서 비정상적으로 낮은 부작용 발생률 (<3%)로 인해 불균형이 나타났습니다. 이는 bexotegrast 치료 그룹 (7%)과 위약 그룹 (10%) 간의 부작용이 비슷했던 2a 단계 INTEGRIS-IPF 임상 시험과 대조적입니다.
회사는 전체 데이터를 분석하고 폐섬유증 및 기타 비호흡기 적응증에 대한 낮은 용량의 추가 2b 연구를 고려할 계획입니다. 한편, Pliant는 현재 1상 시험 중인 항암제 PLN-101095를 포함한 다른 자산 개발을 계속하고 있습니다.
Pliant Therapeutics (PLRX) a interrompu son essai BEACON-IPF de phase 2b sur le bexotegrast chez des patients atteints de fibrose pulmonaire idiopathique (IPF) en raison de préoccupations concernant la sécurité, malgré des signes d'efficacité précoce en capacité vitale forcée (FVC). L'interruption est survenue après des examens par le Comité de Surveillance de la Sécurité des Données de l'essai et un panel d'experts externes.
L'essai, avec une durée d'exposition moyenne d'environ 17 semaines, a montré des événements indésirables liés à l'IPF comparables (environ 10%) dans les deux groupes de doses. Cependant, un déséquilibre a été noté en raison de taux d'événements indésirables anormalement bas (<3%) dans le groupe placebo. Cela contraste avec l'essai de phase 2a INTEGRIS-IPF, où les événements indésirables étaient similaires entre les groupes traités avec bexotegrast (7%) et placebo (10%).
L'entreprise prévoit d'analyser les données complètes et d'envisager des études supplémentaires de phase 2b avec des doses plus faibles pour la fibrose pulmonaire et d'autres indications non respiratoires. Pendant ce temps, Pliant continue de développer d'autres actifs, y compris PLN-101095 en oncologie, actuellement en essais de phase 1.
Pliant Therapeutics (PLRX) hat die BEACON-IPF Phase 2b Studie zu bexotegrast bei Patienten mit idiopathischer Lungenfibrose (IPF) aufgrund von Sicherheitsbedenken eingestellt, obwohl frühe Anzeichen von Wirksamkeit in der forcierten Vitalkapazität (FVC) gezeigt wurden. Die Einstellung erfolgte nach Überprüfungen durch das Data Safety Monitoring Board der Studie und ein externes Expertengremium.
Die Studie, mit einer durchschnittlichen Expositionsdauer von etwa 17 Wochen, zeigte vergleichbare IPF-bezogene unerwünschte Ereignisse (rund 10%) in beiden Dosisgruppen. Es wurde jedoch ein Ungleichgewicht festgestellt, da die unerwünschten Ereignisraten in der Placebo-Gruppe ungewöhnlich niedrig (<3%) waren. Dies steht im Gegensatz zur Phase 2a INTEGRIS-IPF Studie, in der die unerwünschten Ereignisse zwischen der mit bexotegrast behandelten (7%) und der Placebo-Gruppe (10%) ähnlich waren.
Das Unternehmen plant, die vollständigen Daten zu analysieren und weitere Phase 2b Studien mit niedrigeren Dosen für Lungenfibrose und andere nicht-respiratorische Indikationen in Betracht zu ziehen. In der Zwischenzeit entwickelt Pliant weiterhin andere Vermögenswerte, darunter PLN-101095 in der Onkologie, das sich derzeit in Phase 1 Studien befindet.
- Early evidence of efficacy on forced vital capacity (FVC) endpoint
- Continuing development of PLN-101095 in oncology with Phase 1 trial progress
- Potential expansion to non-respiratory indications including liver diseases
- BEACON-IPF Phase 2b trial discontinued due to safety concerns
- Imbalance in IPF-related adverse events between treatment and placebo groups
- Need to potentially lower doses, requiring additional Phase 2b studies
Insights
Pliant Therapeutics' discontinuation of the BEACON-IPF Phase 2b/3 trial represents a significant clinical development setback that substantially impacts the company's near-term prospects. The trial was stopped due to safety concerns - specifically an imbalance in IPF-related adverse events between treatment and placebo groups - despite showing encouraging efficacy signals on the important forced vital capacity (FVC) endpoint.
This paradoxical outcome (efficacy with safety concerns) creates a complex scenario for investors to evaluate. The company appears to be pivoting toward exploring lower doses in future studies, suggesting they believe a therapeutic window may still exist where efficacy can be maintained with improved safety. However, this represents a meaningful delay in their development timeline for bexotegrast.
The 17-week mean exposure duration in the trial provides long-term safety data, complicating the risk assessment. Notably, the company pointed out that the adverse event imbalance may have been partially driven by an unusually low event rate (
Investors should closely monitor the upcoming complete data analysis, which will determine whether bexotegrast has a viable path forward at lower doses or if resources will shift more decisively toward their oncology asset PLN-101095, currently in Phase 1 with interim data expected in Q1 2025.
The discontinuation of BEACON-IPF highlights the significant challenges in developing effective IPF therapies. What's clinically interesting is that this appears to be the first late-stage IPF trial discontinued for safety while simultaneously demonstrating strong efficacy signals on FVC - the gold standard endpoint for IPF trials.
The approximately
This discrepancy between trials suggests potential variability in patient populations or disease progression that complicates interpretation. It's noteworthy that despite the safety concerns, the efficacy signal remained strong enough to mention prominently in this disclosure - suggesting bexotegrast may still have therapeutic potential if the right dose can be identified.
For a devastating disease like IPF with treatment options, finding the optimal therapeutic window is critical. The company's strategy to potentially explore lower doses makes clinical sense, as IPF drug development often requires careful dose optimization to balance efficacy and tolerability. The fact that they're considering non-respiratory indications like liver diseases also indicates potential mechanistic versatility of their αvβ6 integrin inhibitor approach.
SOUTH SAN FRANCISCO, Calif., March 03, 2025 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX) today announced that following a prespecified data review and recommendation by the trial’s independent Data Safety Monitoring Board (DSMB), as well as a secondary review and recommendation by an outside expert panel, Pliant has discontinued the BEACON-IPF Phase 2b trial evaluating bexotegrast in patients with idiopathic pulmonary fibrosis (IPF). While an imbalance in unadjudicated IPF-related adverse events between the treatment and placebo groups led to the discontinuation of the trial, early evidence of efficacy on the forced vital capacity (FVC) endpoint was also observed.
BEACON-IPF is the first late-stage IPF trial to be discontinued for safety while showing strong evidence of efficacy.
The mean exposure duration in BEACON-IPF was approximately 17 weeks. Overall, the percentage of IPF-related adverse events in both dose groups was comparable (approximately
The Company plans to analyze the complete data from the BEACON-IPF trial and evaluate next steps for bexotegrast’s development. Once the full analysis is completed, which should provide a better understanding of the benefit risk profile and therapeutic window of bexotegrast, the Company will consider additional dose-ranging Phase 2b studies with lower doses in pulmonary fibrosis and potentially, other non-respiratory indications, including liver diseases.
Pliant is committed to the development of its other clinical and pipeline assets including PLN-101095 in oncology. The Company is currently enrolling the fourth of five planned dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Interim data from the first three cohorts is expected in the first quarter of 2025.
Pliant would like to thank the BEACON-IPF investigators and their study teams, as well as the members of the Pliant team for their dedication in support of the execution of this trial. The Company also wants to give special thanks to the BEACON-IPF clinical trial participants, their families and support networks for their participation in, and support of BEACON-IPF.
About BEACON-IPF
BEACON-IPF is a 52-week, multinational, randomized, dose-ranging, double-blind, placebo-controlled trial evaluating bexotegrast at once-daily doses of 160 mg or 320 mg in patients with idiopathic pulmonary fibrosis (IPF).
About Pliant Therapeutics, Inc.
Pliant Therapeutics is a late-stage biopharmaceutical company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvß6 and αvß1 integrins that is in development in the lead indication for the treatment of idiopathic pulmonary fibrosis, or IPF. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and Orphan Drug Designation from the European Medicines Agency in IPF. Pliant is conducting a Phase 1 study for its third clinical program, PLN-101095, a small molecule, dual-selective inhibitor of αvß8 and αvß1 integrins, that is being developed for the treatment of solid tumors. In addition, Pliant has received regulatory clearance for the conduct of a Phase 1 study of PLN-101325, a monoclonal antibody agonist of integrin α7β1 targeting muscular dystrophies.
For additional information, please visit: www.PliantRx.com. Follow us on social media X, LinkedIn, and Facebook.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those regarding the Company’s preliminary analysis of data from the BEACON-IPF trial, the Company’s intent to complete a more full analysis and potential next steps for bexotegrast development, as well as statements regarding the development of the Company’s other clinical and pipeline assets. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant Therapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the development and commercialization of our product candidates, including analysis of the complete data from the BEACON-IPF trial, any delays in our ongoing or planned preclinical or clinical trials, the risks inherent in the drug development process, and our capital requirements and the need for additional financing, including the anticipated lack of availability of additional funds under the current terms of our loan facility. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Quarterly Report on Form 10-Q for the period ended September 30, 2024, which is available on the SEC's website at www.sec.gov, as updated by our Annual Report on Form 10-K for the year ended December 31, 2024, which we expect to file with the SEC today. Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Investor and Media Contact:
Christopher Keenan
Vice President, Investor Relations and Corporate Communications
Pliant Therapeutics, Inc.
ir@pliantrx.com
FAQ
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