Acurx Receives Positive Regulatory Guidance from EMA for Ibezapolstat Phase 3 Program for C. Difficile Infection (CDI)
Acurx Pharmaceuticals (NASDAQ: ACXP) has received positive regulatory guidance from the European Medicines Agency (EMA) for its ibezapolstat Phase 3 program targeting C. difficile Infection (CDI). The EMA's Scientific Advice Procedure confirmed that the clinical, non-clinical, and CMC information package supports advancing to Phase 3 trials.
The company plans two Phase 3 non-inferiority pivotal trials versus vancomycin, with an estimated 450 subjects in the Modified Intent-To-Treat population randomized 1:1. The primary endpoint will measure Clinical Cure of CDI after 10 days of oral treatment, with additional assessment of CDI recurrence reduction. If non-inferiority is demonstrated, superiority testing will follow.
Ibezapolstat has already received FDA QIDP and Fast-Track Designation, and Acurx holds EMA SME designation. The company is preparing to request regulatory guidance for clinical trials in Japan, Canada, and the United Kingdom.
Acurx Pharmaceuticals (NASDAQ: ACXP) ha ricevuto indicazioni positive dalle autorità di regolamentazione europee (EMA) per il suo programma di Fase 3 con ibezapolstat, mira a trattare l'Infezione da C. difficile (CDI). La Procedura di Consiglio Scientifico dell'EMA ha confermato che il pacchetto informativo clinico, non clinico e CMC supporta l'avanzamento verso gli studi di Fase 3.
L'azienda prevede di svolgere due studi pivotali di Fase 3 di non inferiorità rispetto alla vancomicina, con un campione stimato di 450 soggetti nella popolazione Modificata di Intento di Trattamento randomizzati 1:1. L'endpoint primario misurerà la Guarigione Clinica della CDI dopo 10 giorni di trattamento orale, con una valutazione aggiuntiva della riduzione della ricorrenza della CDI. Se sarà dimostrata la non inferiorità, seguiranno test di superiorità.
Ibezapolstat ha già ricevuto la designazione QIDP e Fast-Track dalla FDA, e Acurx detiene la designazione SME dell'EMA. L'azienda si sta preparando a richiedere indicazioni regolatorie per studi clinici in Giappone, Canada e Regno Unito.
Acurx Pharmaceuticals (NASDAQ: ACXP) ha recibido orientación regulatoria positiva de la Agencia Europea de Medicamentos (EMA) para su programa de Fase 3 con ibezapolstat, dirigido a la Infección por C. difficile (CDI). El Procedimiento de Asesoramiento Científico de la EMA confirmó que el paquete de información clínica, no clínica y CMC apoya el avance a ensayos de Fase 3.
La compañía planea realizar dos ensayos pivotales de Fase 3 de no inferioridad en comparación con la vancomicina, con un estimado de 450 sujetos en la población Modificada de Intención de Tratar, aleatorizados 1:1. El objetivo primario medirá la Curación Clínica de la CDI tras 10 días de tratamiento oral, con una evaluación adicional de la reducción de la recurrencia de la CDI. Si se demuestra la no inferioridad, se procederá a pruebas de superioridad.
Ibezapolstat ya ha recibido la designación QIDP y Fast-Track de la FDA, y Acurx tiene la designación SME de la EMA. La compañía se está preparando para solicitar orientación regulatoria para ensayos clínicos en Japón, Canadá y el Reino Unido.
Acurx Pharmaceuticals (NASDAQ: ACXP)는 유럽 의약품청 (EMA)으로부터 C. difficile 감염 (CDI)을 목표로 하는 ibezapolstat 3상 프로그램에 대한 긍정적인 규제 지침을 받았습니다. EMA의 과학 자문 절차는 임상적, 비임상적, CMC 정보 패키지가 3상 시험으로 진행하는 것을 지원한다는 것을 확인했습니다.
회사는 반코마이신과 비교한 비열등성의 3상 주요 시험을 두 건 계획하고 있으며, 수정된 의도-치료(population - Modified Intent-To-Treat)의 450명의 피험자가 1:1로 무작위 배정될 예정입니다. 주요 목표는 10일 간의 경구 치료 후 CDI의 임상적 치료를 측정하는 것이며, CDI 재발 감소에 대한 추가 평가가 이루어질 것입니다. 비열등성이 입증될 경우 우수성 검사가 진행됩니다.
Ibzepolstat는 이미 FDA의 QIDP 및 빠른 통로 지정을 받았으며, Acurx는 EMA의 SME 지정을 보유하고 있습니다. 이 회사는 일본, 캐나다 및 영국에서 임상 시험을 위한 규제 지침을 요청할 준비를 하고 있습니다.
Acurx Pharmaceuticals (NASDAQ: ACXP) a reçu des conseils réglementaires positifs de l'Agence européenne des médicaments (EMA) pour son programme de phase 3 sur l'ibezapolstat ciblant l'infection à C. difficile (CDI). La procédure de conseil scientifique de l'EMA a confirmé que le dossier d'informations cliniques, non cliniques et CMC soutient la progression vers les essais de phase 3.
L'entreprise prévoit de mener deux essais pivotaux de phase 3 de non-infériorité par rapport à la vancomycine, avec un échantillon estimé de 450 sujets dans la population modifiée d'intention de traiter, randomisés 1:1. Le critère principal mesurera la guérison clinique de la CDI après 10 jours de traitement oral, avec une évaluation supplémentaire de la réduction de la récurrence de la CDI. Si la non-infériorité est démontrée, des tests de supériorité suivront.
Ibzepolstat a déjà reçu la désignation QIDP et Fast-Track de la FDA, et Acurx détient la désignation SME de l'EMA. L'entreprise se prépare à demander des conseils réglementaires pour des essais cliniques au Japon, au Canada et au Royaume-Uni.
Acurx Pharmaceuticals (NASDAQ: ACXP) hat positive regulatorische Hinweise von der Europäischen Arzneimittel-Agentur (EMA) für sein Phase-3-Programm mit ibezapolstat erhalten, das sich auf die C. difficile-Infektion (CDI) konzentriert. Das wissenschaftliche Beratungverfahren der EMA bestätigte, dass das klinische, nicht-klinische und CMC-Informationspaket den Fortschritt zu Phase-3-Studien unterstützt.
Das Unternehmen plant zwei wegweisende Phase-3-Studien zur Nichinferiorität im Vergleich zu Vancomycin, mit schätzungsweise 450 Probanden in der modifizierten Absicht-zur-Behandlung-Population, die 1:1 randomisiert werden. Der primäre Endpunkt wird die klinische Heilung von CDI nach 10 Tagen oraler Behandlung messen, mit einer zusätzlichen Bewertung der Rückfallreduktion von CDI. Sollte Nichinferiorität nachgewiesen werden, wird eine Überlegenheitsprüfung folgen.
Ibzepolstat hat bereits die QIDP- und Fast-Track-Designation der FDA erhalten, und Acurx hält die SME-Designation der EMA. Das Unternehmen bereitet sich darauf vor, regulatorische Hinweise für klinische Studien in Japan, Kanada und dem Vereinigten Königreich anzufordern.
- Received positive EMA guidance supporting Phase 3 program advancement
- Previously secured FDA QIDP and Fast-Track Designation
- Obtained EMA SME designation providing fee incentives and support
- Clear regulatory pathway established for both US NDA and EU Marketing Authorization
- Potential for superiority testing if non-inferiority to vancomycin is demonstrated
- Large Phase 3 trial requirement of 450 subjects indicates significant clinical costs ahead
- Must demonstrate non-inferiority before attempting superiority claims
Insights
The EMA's positive feedback on ibezapolstat's Phase 3 program represents a important milestone for Acurx. The regulatory alignment between EMA and FDA significantly de-risks the development pathway. The Phase 3 trial design with 450 subjects in the mITT population is robust and well-powered to demonstrate non-inferiority to vancomycin, with potential for superiority analysis.
The dual QIDP and Fast-Track designations from FDA, coupled with EMA's SME status, provide accelerated review potential and cost benefits. The two planned Phase 3 non-inferiority trials against vancomycin, measuring both Clinical Cure and recurrence rates, address key clinical needs in CDI treatment. The potential expansion into Japan, Canada and UK markets enhances commercial prospects.
The harmonized regulatory pathway across EMA and FDA is particularly noteworthy. The written responses format indicates strong confidence in the development program, as agencies typically reserve written responses for well-designed proposals requiring minimal discussion. The CMC package acceptance and agreement on trial design parameters - including endpoints, population selection and statistical analysis plan - suggests a mature development program.
The Modified Intent-To-Treat (mITT) population approach aligns with current regulatory standards for antibiotic trials. The 1:1 randomization ratio and inclusion of superiority testing options demonstrate strategic trial design that maximizes regulatory and commercial potential.
For a micro-cap company (
The SME designation from EMA provides valuable fee reductions and regulatory support, important for resource optimization. The comprehensive Phase 3 program design, while ambitious for a company of this size, creates multiple value inflection points that could attract strategic partners or acquisition interest.
- Acurx has now received positive written responses from the EMA (European Medicines Agency) under its Scientific Advice Procedure that the clinical, non-clinical and CMC (Chemistry Manufacturing and Controls) information package submitted supports advancement of the ibezapolstat Phase 3 program
- The responses also included guidance on ibezapolstat's regulatory pathway for a Marketing Authorization Application for ibezapolstat in CDI
- With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program
- 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
Acurx's Executive Chairman, Bob DeLuccia, stated: "We are appreciative of the EMA's constructive suggestions, and we will proactively incorporate them into our global registration plan. He further stated: "We are very pleased with the latest favorable communications from both regulatory agencies which provide a straightforward international roadmap for conduct of our Phase 3 program and ultimate requirements for a US NDA (New Drug Application) submission and EU Marketing Authorization Application."
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 previously announced it had a successful End of Phase 2 Meeting achieving agreement with FDA on non-clinical and clinical Phase 3-readiness, including written positive feedback regarding acceptability of its CMC (Chemistry Manufacturing and Controls) plan and data package proposed to support the Phase 3 clinical program. In addition, Acurx had initiated the Scientific Advice procedure with the EMA to discuss the readiness for initiation of the Phase 3 clinical program in the EU. Acurx is 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. The primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population. 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
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
New England Journal of Medicine). Recent estimates suggest C. difficile approaches 500,000 infections annually in the
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:10.3390/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.
FAQ
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