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 autorit脿 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 inferiorit脿 rispetto alla vancomicina, con un campione stimato di 450 soggetti nella popolazione Modificata di Intento di Trattamento randomizzati 1:1. L'endpoint primario misurer脿 la Guarigione Clinica della CDI dopo 10 giorni di trattamento orale, con una valutazione aggiuntiva della riduzione della ricorrenza della CDI. Se sar脿 dimostrata la non inferiorit脿, seguiranno test di superiorit脿.
Ibezapolstat ha gi脿 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 orientaci贸n regulatoria positiva de la Agencia Europea de Medicamentos (EMA) para su programa de Fase 3 con ibezapolstat, dirigido a la Infecci贸n por C. difficile (CDI). El Procedimiento de Asesoramiento Cient铆fico de la EMA confirm贸 que el paquete de informaci贸n cl铆nica, no cl铆nica y CMC apoya el avance a ensayos de Fase 3.
La compa帽铆a planea realizar dos ensayos pivotales de Fase 3 de no inferioridad en comparaci贸n con la vancomicina, con un estimado de 450 sujetos en la poblaci贸n Modificada de Intenci贸n de Tratar, aleatorizados 1:1. El objetivo primario medir谩 la Curaci贸n Cl铆nica de la CDI tras 10 d铆as de tratamiento oral, con una evaluaci贸n adicional de la reducci贸n de la recurrencia de la CDI. Si se demuestra la no inferioridad, se proceder谩 a pruebas de superioridad.
Ibezapolstat ya ha recibido la designaci贸n QIDP y Fast-Track de la FDA, y Acurx tiene la designaci贸n SME de la EMA. La compa帽铆a se est谩 preparando para solicitar orientaci贸n regulatoria para ensayos cl铆nicos en Jap贸n, Canad谩 y el Reino Unido.
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Acurx Pharmaceuticals (NASDAQ: ACXP) a re莽u des conseils r茅glementaires positifs de l'Agence europ茅enne des m茅dicaments (EMA) pour son programme de phase 3 sur l'ibezapolstat ciblant l'infection 脿 C. difficile (CDI). La proc茅dure de conseil scientifique de l'EMA a confirm茅 que le dossier d'informations cliniques, non cliniques et CMC soutient la progression vers les essais de phase 3.
L'entreprise pr茅voit de mener deux essais pivotaux de phase 3 de non-inf茅riorit茅 par rapport 脿 la vancomycine, avec un 茅chantillon estim茅 de 450 sujets dans la population modifi茅e d'intention de traiter, randomis茅s 1:1. Le crit猫re principal mesurera la gu茅rison clinique de la CDI apr猫s 10 jours de traitement oral, avec une 茅valuation suppl茅mentaire de la r茅duction de la r茅currence de la CDI. Si la non-inf茅riorit茅 est d茅montr茅e, des tests de sup茅riorit茅 suivront.
Ibzepolstat a d茅j脿 re莽u la d茅signation QIDP et Fast-Track de la FDA, et Acurx d茅tient la d茅signation SME de l'EMA. L'entreprise se pr茅pare 脿 demander des conseils r茅glementaires pour des essais cliniques au Japon, au Canada et au Royaume-Uni.
Acurx Pharmaceuticals (NASDAQ: ACXP) hat positive regulatorische Hinweise von der Europ盲ischen Arzneimittel-Agentur (EMA) f眉r sein Phase-3-Programm mit ibezapolstat erhalten, das sich auf die C. difficile-Infektion (CDI) konzentriert. Das wissenschaftliche Beratungverfahren der EMA best盲tigte, dass das klinische, nicht-klinische und CMC-Informationspaket den Fortschritt zu Phase-3-Studien unterst眉tzt.
Das Unternehmen plant zwei wegweisende Phase-3-Studien zur Nichinferiorit盲t im Vergleich zu Vancomycin, mit sch盲tzungsweise 450 Probanden in der modifizierten Absicht-zur-Behandlung-Population, die 1:1 randomisiert werden. Der prim盲re Endpunkt wird die klinische Heilung von CDI nach 10 Tagen oraler Behandlung messen, mit einer zus盲tzlichen Bewertung der R眉ckfallreduktion von CDI. Sollte Nichinferiorit盲t nachgewiesen werden, wird eine 脺berlegenheitspr眉fung folgen.
Ibzepolstat hat bereits die QIDP- und Fast-Track-Designation der FDA erhalten, und Acurx h盲lt die SME-Designation der EMA. Das Unternehmen bereitet sich darauf vor, regulatorische Hinweise f眉r klinische Studien in Japan, Kanada und dem Vereinigten K枚nigreich 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. (,听)
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听 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听 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听the听Ibezapolstat Phase 2听Clinical听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)听at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. (听) 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 卤 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 卤 2 days post EOT (ECC56) and 84 卤 2 days post EOT (ECC84) in patients who consented to extended observation. In the Phase 2b trial,
About听Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C.听difficile Infection (CDI). Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS庐) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development听by听Acurx to treat bacterial infections. Ibezapolstat's听unique spectrum of听activity, which听includes听颁.听诲颈蹿蹿颈肠颈濒别听but spares听other听Firmicutes听and听the听important Actinobacteria听phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the
About听Clostridioides听difficile听Infection听(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.听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听the听Microbiome听in听颁.听诲颈蹿蹿颈肠颈濒别听Infection听(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 颁.听诲颈蹿蹿颈肠颈濒别, 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听C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of听C. difficile听spores and听thereby increase听the听risk听of听recurrent听CDI听after听successful听treatment听of听an听initial听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听Acurx Pharmaceuticals,听Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new听class听of听small听molecule antibiotics听for听difficult-to-treat听bacterial听infections.听The听Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS庐) 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听death.听Its听R&D听pipeline includes听antibiotic听product candidates听that听target听Gram-positive bacteria,听including听Clostridioides听difficile, methicillin-resistant Staphylococcus听aureus听(MRSA), vancomycin听resistant听Enterococcus听(VRE),听drug-resistant听Streptococcus听pneumoniae听(DRSP) and听B.听anthracis听(anthrax; a Bioterrorism Category A Threat-Level pathogen). Acurx's lead product candidate, ibezapolstat, for the treatment of 颁.听诲颈蹿蹿颈肠颈濒别听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听learn more听about听Acurx Pharmaceuticals听and听its听product听pipeline,听please听visit .
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听Contact:
Acurx听Pharmaceuticals,听Inc.听
David P.听Luci, President & CEO听
Tel: 917-533-1469
Email:听davidluci@acurxpharma.com
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SOURCE Acurx Pharmaceuticals, Inc.
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