Acurx Updates Phase 3 Readiness for Ibezapolstat in C. difficile Infection Based on Recent FDA and EMA Communications
Acurx Pharmaceuticals has provided updates on the Phase 3 readiness of its lead antibiotic candidate, ibezapolstat, for treating C. difficile Infection (CDI). The FDA has given positive feedback on the proposed Chemistry Manufacturing and Controls (CMC) plan, and Acurx is awaiting final advice from the European Medicines Agency (EMA) for the Phase 3 clinical program in the EU. The company is also discussing pediatric development plans with both the FDA and EU authorities. Acurx is preparing to request regulatory guidance for initiating clinical trials in Japan, Canada, and the UK.
Phase 3 international trial planning is advancing, utilizing AI to identify optimal clinical trial sites. Ibezapolstat has previously received FDA QIDP and Fast-Track Designation and SME designation from the EMA. The Phase 3 trial will involve approximately 450 subjects, comparing ibezapolstat to vancomycin, with a focus on achieving clinical cure and reducing CDI recurrence. The Executive Chairman expressed confidence in the trial's success, which would pave the way for US NDA submission and EU Marketing Authorization.
Acurx Pharmaceuticals ha fornito aggiornamenti sulla prontezza della Fase 3 del suo principale candidato antibiotico, ibezapolstat, per il trattamento dell'infezione da C. difficile (CDI). La FDA ha fornito feedback positivi sul piano proposto di Chimica, Produzione e Controlli (CMC), e Acurx sta aspettando ulteriori consigli dall'Agenzia Europea dei Medicinali (EMA) per il programma clinico di Fase 3 nell'UE. L'azienda sta anche discutendo piani di sviluppo pediatrico con le autorità della FDA e dell'UE. Acurx si sta preparando a richiedere indicazioni regolatorie per avviare studi clinici in Giappone, Canada e Regno Unito.
La pianificazione della sperimentazione internazionale di Fase 3 sta procedendo, sfruttando l'IA per identificare i siti ottimali per le prove cliniche. Ibezapolstat ha ricevuto in precedenza la designazione QIDP e Fast-Track dalla FDA e la designazione SME dall'EMA. La sperimentazione di Fase 3 coinvolgerà circa 450 soggetti, confrontando ibezapolstat con la vancomicina, con un focus sul raggiungimento della cura clinica e sulla riduzione della ricorrenza della CDI. Il presidente esecutivo ha espresso fiducia nel successo della sperimentazione, che aprirebbe la strada per la sottomissione del NDA negli USA e per l'autorizzazione al commercio nell'UE.
Acurx Pharmaceuticals ha proporcionado actualizaciones sobre la preparación para la Fase 3 de su principal candidato a antibiótico, ibezapolstat, para el tratamiento de la infección por C. difficile (CDI). La FDA ha dado comentarios positivos sobre el plan propuesto de Química, Fabricación y Controles (CMC), y Acurx está esperando el consejo final de la Agencia Europea de Medicamentos (EMA) para el programa clínico de Fase 3 en la UE. La compañía también está discutiendo planes de desarrollo pediátrico con las autoridades de la FDA y la UE. Acurx se está preparando para solicitar orientación regulatoria para iniciar ensayos clínicos en Japón, Canadá y el Reino Unido.
La planificación del ensayo internacional de Fase 3 está avanzando, utilizando inteligencia artificial para identificar los sitios óptimos para los ensayos clínicos. Ibezapolstat había recibido anteriormente las designaciones QIDP y Fast-Track de la FDA y la designación SME de la EMA. El ensayo de Fase 3 involucrará aproximadamente a 450 sujetos, comparando ibezapolstat con vancomicina, con un enfoque en lograr la cura clínica y reducir la recurrencia de la CDI. El presidente ejecutivo expresó confianza en el éxito del ensayo, lo que allanaría el camino para la presentación de la NDA en EE. UU. y la autorización de marketing en la UE.
Acurx Pharmaceuticals는 ibezapolstat의 3상 준비 상태에 대한 업데이트를 제공했습니다. 이 제품은 C. difficile 감염(CDI) 치료를 위한 주요 항생제 후보입니다. FDA는 제안된 화학, 제조 및 품질 관리(CMC) 계획에 대해 긍정적인 피드백을 주었으며, Acurx는 EU 내 3상 임상 프로그램에 대한 최종 조언을 유럽 의약품청(EMA)에서 기다리고 있습니다. 이 회사는 또한 FDA 및 EU 당국과 함께 소아 개발 계획에 대해 논의하고 있습니다. Acurx는 일본, 캐나다 및 영국에서 임상 시험을 시작하기 위한 규제 지침 요청을 준비하고 있습니다.
3상 국제 임상 시험 계획은 최적의 시험 사이트를 확인하기 위해 AI를 활용하여 진행되고 있습니다. Ibezapolstat는 이전에 FDA로부터 QIDP 및 고속 처리 지정, 그리고 EMA로부터 SME 지정을 받았습니다. 3상 임상 시험은 약 450명의 피험자를 포함하여 ibezapolstat과 반코마이신을 비교하며, 임상적 치료 달성과 CDI 재발 감소에 중점을 두고 진행됩니다. 회장직은 시험의 성공에 대한 신뢰를 표명하며, 이는 미국 NDA 제출 및 EU 마케팅 허가를 위한 길을 열 것이라고 밝혔습니다.
Acurx Pharmaceuticals a fourni des mises à jour sur la préparation de la phase 3 de son principal candidat antibiotique, ibezapolstat, pour le traitement de l'infection à C. difficile (CDI). La FDA a donné des retours positifs sur le plan proposé de Chimie, Fabrication et Contrôles (CMC), et Acurx attend des conseils finaux de l'Agence Européenne des Médicaments (EMA) pour le programme clinique de la phase 3 dans l'UE. La société discute également des plans de développement pédiatrique avec les autorités de la FDA et de l'UE. Acurx se prépare à demander des orientations réglementaires pour initier des essais cliniques au Japon, au Canada et au Royaume-Uni.
La planification de l'essai international de phase 3 progresse, utilisant l'IA pour identifier les sites d'essai cliniques optimaux. Ibezapolstat a précédemment reçu la désignation QIDP et Fast-Track de la FDA ainsi que la désignation SME de l'EMA. L'essai de phase 3 impliquera environ 450 sujets, comparant ibezapolstat à la vancomycine, avec un accent sur l'obtention d'une guérison clinique et la réduction de la récidive de la CDI. Le président exécutif a exprimé sa confiance dans le succès de l'essai, qui ouvrirait la voie à la soumission de la NDA aux États-Unis et à l'autorisation de mise sur le marché en UE.
Acurx Pharmaceuticals hat Updates zur Bereitstellung der Phase 3 für seinen Hauptkandidaten Antibiotikum ibezapolstat zur Behandlung der C. difficile-Infektion (CDI) bereitgestellt. Die FDA hat positives Feedback zum vorgeschlagenen Plan für Chemie, Herstellung und Kontrollen (CMC) gegeben, und Acurx wartet auf endgültige Hinweise von der Europäischen Arzneimittel-Agentur (EMA) für das klinische Programm der Phase 3 in der EU. Das Unternehmen diskutiert auch pädiatrische Entwicklungspläne mit den Behörden der FDA und der EU. Acurx bereitet sich darauf vor, regulatorische Leitlinien für die Einleitung klinischer Studien in Japan, Kanada und dem Vereinigten Königreich anzufordern.
Die Planung der internationalen Phase-3-Studie schreitet voran, wobei KI genutzt wird, um optimale klinische Prüfstellen zu identifizieren. Ibezapolstat hat zuvor die QIDP- und Fast-Track-Zulassung von der FDA sowie die SME-Zulassung der EMA erhalten. Die Phase-3-Studie wird etwa 450 Probanden umfassen, die ibezapolstat mit Vancomycin vergleichen, wobei der Schwerpunkt auf der Erreichung einer klinischen Heilung und der Verringerung der CDI-Wiederholung liegt. Der Vorsitzende äußerte Vertrauen in den Erfolg der Studie, die den Weg für die NDA-Einreichung in den USA und die Marktzulassung in der EU ebnen würde.
- FDA positive feedback on CMC plan.
- Advancing Phase 3 trial planning using AI.
- Awaiting final EMA advice for Phase 3 in the EU.
- Preparing regulatory guidance requests for trials in Japan, Canada, and the UK.
- Ibezapolstat received FDA QIDP and Fast-Track Designation.
- Ibezapolstat received SME designation from EMA.
- No final written advice from EMA yet.
Insights
The FDA and EMA communications represent significant regulatory progress for ibezapolstat. The positive feedback on CMC and agreement on Phase 3 trial design demonstrates strong clinical development positioning. The planned 450-patient Phase 3 trial with modified intent-to-treat analysis aligns with both FDA and EMA requirements, streamlining the path to potential dual market approvals.
The trial's dual-purpose design to evaluate both clinical cure and recurrence reduction is strategically important, as CDI recurrence remains a major clinical challenge. The potential for superiority testing against vancomycin, if non-inferiority is demonstrated, could provide a compelling competitive advantage in the
The QIDP and Fast-Track designations, combined with EMA's SME benefits, suggest an expedited regulatory pathway with reduced costs - important for a company with
The regulatory strategy demonstrates sophisticated planning with synchronized FDA/EMA approaches. The written communications format indicates strong preliminary data and submissions, as agencies typically reserve this efficient response method for well-prepared applications. The agreement on mITT population analysis shows careful consideration of both US and EU requirements, potentially avoiding costly protocol amendments.
The expansion into Japan, Canada and UK markets through additional regulatory consultations suggests a comprehensive global strategy. The pediatric development planning aligns with regulatory requirements for both markets, potentially expanding the drug's eventual commercial reach. The SME designation provides valuable fee reductions and regulatory support, optimizing development resources.
- Following the previously announced successful End of Phase 2 Meeting achieving agreement with FDA on non-clinical and clinical Phase 3-readiness, Acurx has now also received written positive feedback from FDA regarding acceptability of our CMC (Chemistry Manufacturing and Controls) plan and data package proposed to support the Phase 3 clinical program
- Acurx has initiated the Scientific Advice procedure with the European Medicines Agency (EMA) to discuss the readiness for initiation of the Phase 3 clinical program in the European Union (EU). Acurx has been notified that we should expect to receive the final written advice letter in the coming few weeks
- Acurx is also in the process of discussing the pediatric development plans for ibezapolstat in C. difficile Infection with FDA and EU health authorities, per regulatory requirements.
- Phase 3 international trial planning continues to advance, using AI and other state-of-the-art techniques to identify and qualify clinical trial sites with the highest potential for patient enrollment
- Acurx is also preparing to request regulatory guidance to initiate clinical trials in
Japan ,Canada and theUnited Kingdom - Ibezapolstat has previously been granted FDA QIDP and Fast-Track Designation from FDA and Acurx has received SME (Small and Medium-sized Enterprise) designation by the EMA to benefit from fee incentives and other support from the EMA for EU Marketing Authorization
Written communications are used by both regulatory agencies in lieu of face-to-face or teleconference/video conferences when these agencies determine that a written response to the sponsor's questions would be the most appropriate means for providing feedback and advice to the sponsor. (FDA Guidance on Formal Meetings, EMA Guidance on Centralised Procedure)
Acurx's Executive Chairman, Bob DeLuccia, stated: "We are very pleased with these latest favorable communications from both regulatory agencies and in our opinion are a testament to the strength of our clinical data to date, our robust regulatory submissions, and adherence to current regulatory guidance." He further added: "We anticipate, and are confident, that with final EMA advice for our ibezapolstat Phase 3 trials for adult patients with CDI and the pediatric development plans from both regulatory agencies, Acurx will have a clear international roadmap for conduct of our Phase 3 program and, if successful, requirements for US NDA submission and EU Marketing Authorization."
Acurx has previously announced that it had a successful FDA End-of-Phase 2 Meeting and Phase 3 Readiness for ibezapolstat for the Treatment of C. difficile Infection. Agreement with FDA was reached on key elements to move forward with its international Phase 3 clinical trial program. Agreement was also reached with FDA on the complete non-clinical and clinical development plan for filing of a New Drug Application (NDA) for marketing approval. Planning continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI). Acurx is also preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, to be followed by requests to be submitted in the
Key elements for the two Phase 3, non-inferiority, pivotal trials were confirmed and included agreement on the protocol design, patient population, primary and secondary endpoints, and size of the registration safety database. Based on FDA recommendations, and in anticipation of an EMA Scientific Advice Meeting, the primary efficacy analysis will be performed using a Modified Intent-To-reat (mITT) population consistent with EMA requirements. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment, but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.
About the Ibezapolstat Phase 2 Clinical Trial
The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (Link to Clinicaltrials.gov/NCT042447542) This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. from study centers in the United States. In the Phase 2a trial segment,10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (
In the Phase 2b trial segment, which was discontinued due to success, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. The Company previously reported that the overall observed Clinical Cure rate in the combined Phase 2 trials in patients with CDI was
There were no drug-related treatment withdrawals or no drug-related serious adverse events, or other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients experienced Clinical Cure. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of
In the Phase 2 clinical trial (both trial segments), the Company also evaluated pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also recently reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 12 patients who agreed to be followed up to three months following Clinical Cure of their infection, 5 of 5 IBZ patients experienced no recurrence of infection. In the vancomycin control arm of the trial, 7 of 7 patients experienced no recurrence of infection. ECC success is defined as a clinical cure at the TOC visit (i.e., at least 48 hours post EOT) and no recurrence of CDI within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who consented to extended observation. In the Phase 2b trial,
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the
About Clostridioides difficile Infection (CDI)
According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in
About the Microbiome in C. difficile Infection (CDI) and Bile Acid Metabolism
C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020, 8, 200; doi: 0.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa. Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (CID, 2022). In the Ph2b trial, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids, and higher beneficial ratio of secondary to primary bile acids than vancomycin-treated patients.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram-positive specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE), drug-resistant Streptococcus pneumoniae (DRSP) and B. anthracis (anthrax; a Bioterrorism Category A Threat-Level pathogen). Acurx's lead product candidate, ibezapolstat, for the treatment of C. difficile Infection is Phase 3 ready with plans in progress to begin international clinical trials next year. The Company's preclinical pipeline includes development of an oral product candidate for treatment of ABSSSI (Acute Bacterial Skin and Skin Structure Infections), upon which a development program for treatment of inhaled anthrax is being planned in parallel.
To learn more about Acurx Pharmaceuticals and its product pipeline, please visit www.acurxpharma.com.
Forward-Looking Statements
Any statements in this press release about our future expectations, plans and prospects, including statements regarding our strategy, future operations, prospects, plans and objectives, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether ibezapolstat will benefit from the QIDP designation; whether ibezapolstat will advance through the clinical trial process on a timely basis; whether the results of the clinical trials of ibezapolstat will warrant the submission of applications for marketing approval, and if so, whether ibezapolstat will receive approval from the FDA or equivalent foreign regulatory agencies where approval is sought; whether, if ibezapolstat obtains approval, it will be successfully distributed and marketed; and other risks and uncertainties described in the Company's annual report filed with the Securities and Exchange Commission on Form 10-K for the year ended December 31, 2023, and in the Company's subsequent filings with the Securities and Exchange Commission. Such forward- looking statements speak only as of the date of this press release, and Acurx disclaims any intent or obligation to update these forward-looking statements to reflect events or circumstances after the date of such statements, except as may be required by law.
Investor Contact:
Acurx Pharmaceuticals, Inc.
David P. Luci, President & CEO
Tel: 917-533-1469
Email: davidluci@acurxpharma.com
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SOURCE Acurx Pharmaceuticals, Inc.
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