Acurx Announces Publication of Nonclinical In Vivo Data Differentiating Ibezapolstat's Gut Microbiome Effects from Other Anti-CDI Antibiotics
Acurx Pharmaceuticals (NASDAQ: ACXP) has published groundbreaking research comparing the gut microbiome effects of its lead antibiotic candidate ibezapolstat (IBZ) with other antibiotics used to treat C. difficile Infection (CDI).
The study, published in the Journal of Antimicrobial Agents and Chemotherapeutics, revealed that IBZ caused less disruption to gut microbiome diversity compared to vancomycin (VAN) and metronidazole (MET). The research showed IBZ increased the relative abundance of Bacteroidota and Actinomycetota phyla, with the latter including beneficial bacteria like Bifidobacteria.
Notable differences were observed between IBZ and fidaxomicin (FDX), potentially differentiating these two anti-CDI antibiotics in future studies. IBZ is preparing to advance to international Phase 3 clinical trials for CDI treatment and has received FDA QIDP, Fast-Track Designation, and EMA SME designation.
Acurx Pharmaceuticals (NASDAQ: ACXP) ha pubblicato una ricerca innovativa che confronta gli effetti del microbioma intestinale del suo principale candidato antibiotico ibezapolstat (IBZ) con altri antibiotici utilizzati per trattare l'infezione da C. difficile (CDI).
Lo studio, pubblicato nel Journal of Antimicrobial Agents and Chemotherapeutics, ha rivelato che l'IBZ ha causato meno interruzioni nella diversità del microbioma intestinale rispetto alla vancomicina (VAN) e al metronidazolo (MET). La ricerca ha mostrato che l'IBZ ha aumentato l'abbondanza relativa dei phyla Bacteroidota e Actinomycetota, con quest'ultimo che include batteri benefici come i Bifidobacteria.
Differenze significative sono state osservate tra l'IBZ e la fidaxomicina (FDX), potenzialmente distinguendo questi due antibiotici anti-CDI in studi futuri. L'IBZ si sta preparando a passare a studi clinici internazionali di Fase 3 per il trattamento della CDI e ha ricevuto la designazione QIDP della FDA, la designazione Fast-Track e la designazione SME dell'EMA.
Acurx Pharmaceuticals (NASDAQ: ACXP) ha publicado una investigación innovadora que compara los efectos del microbioma intestinal de su principal candidato a antibiótico ibezapolstat (IBZ) con otros antibióticos utilizados para tratar la infección por C. difficile (CDI).
El estudio, publicado en el Journal of Antimicrobial Agents and Chemotherapeutics, reveló que el IBZ causó menos alteraciones en la diversidad del microbioma intestinal en comparación con la vancomicina (VAN) y el metronidazol (MET). La investigación mostró que el IBZ aumentó la abundancia relativa de los filos Bacteroidota y Actinomycetota, siendo este último un grupo que incluye bacterias beneficiosas como los Bifidobacteria.
Diferencias notables fueron observadas entre el IBZ y la fidaxomicina (FDX), lo que podría diferenciar estos dos antibióticos anti-CDI en estudios futuros. El IBZ se está preparando para avanzar a ensayos clínicos internacionales de Fase 3 para el tratamiento de la CDI y ha recibido la designación QIDP de la FDA, la designación Fast-Track y la designación SME de la EMA.
Acurx Pharmaceuticals (NASDAQ: ACXP)는 주도 항생제 후보인 ibezapolstat (IBZ)의 장내 미생물군에 미치는 영향을 C. difficile 감염(CDI) 치료에 사용되는 다른 항생제와 비교한 혁신적인 연구를 발표했습니다.
이 연구는 Journal of Antimicrobial Agents and Chemotherapeutics에 발표되었으며, IBZ가 반코마이신(VAN) 및 메트로니다졸(MET)에 비해 장내 미생물군의 다양성에 덜 영향을 미친다는 것을 밝혀냈습니다. 연구 결과, IBZ는 Bacteroidota와 Actinomycetota 문(門)의 상대적 풍부성을 증가시켰으며, 후자는 비피도박테리아와 같은 유익한 박테리아를 포함합니다.
IBZ와 피닥소마이신(FDX) 간의 주목할 만한 차이점이 관찰되어, 향후 연구에서 이 두 가지 항-CDI 항생제를 구별할 수 있는 가능성이 있습니다. IBZ는 CDI 치료를 위한 국제 3상 임상 시험으로 진행할 준비를 하고 있으며, FDA의 QIDP, 패스트 트랙 지정 및 EMA의 SME 지정을 받았습니다.
Acurx Pharmaceuticals (NASDAQ: ACXP) a publié une recherche révolutionnaire comparant les effets du microbiome intestinal de son principal candidat antibiotique ibezapolstat (IBZ) avec d'autres antibiotiques utilisés pour traiter l'infection à C. difficile (CDI).
L'étude, publiée dans le Journal of Antimicrobial Agents and Chemotherapeutics, a révélé que l'IBZ a causé moins de perturbations à la diversité du microbiome intestinal par rapport à la vancomycine (VAN) et au métronidazole (MET). La recherche a montré que l'IBZ augmentait l'abondance relative des phylums Bacteroidota et Actinomycetota, ce dernier incluant des bactéries bénéfiques comme les Bifidobacteria.
Des différences notables ont été observées entre l'IBZ et la fidaxomicine (FDX), ce qui pourrait différencier ces deux antibiotiques anti-CDI dans de futures études. L'IBZ se prépare à avancer vers des essais cliniques internationaux de phase 3 pour le traitement de la CDI et a reçu la désignation QIDP de la FDA, la désignation Fast-Track et la désignation SME de l'EMA.
Acurx Pharmaceuticals (NASDAQ: ACXP) hat eine bahnbrechende Forschung veröffentlicht, die die Auswirkungen des Mikrobioms im Darm seines führenden Antibiotika-Kandidaten ibezapolstat (IBZ) mit anderen Antibiotika vergleicht, die zur Behandlung von C. difficile-Infektionen (CDI) eingesetzt werden.
Die Studie, die im Journal of Antimicrobial Agents and Chemotherapeutics veröffentlicht wurde, zeigte, dass IBZ weniger Störungen der Diversität des Mikrobioms im Darm verursachte als Vancomycin (VAN) und Metronidazol (MET). Die Forschung ergab, dass IBZ die relative Häufigkeit der Phyla Bacteroidota und Actinomycetota erhöhte, wobei letzteres nützliche Bakterien wie Bifidobacterien umfasst.
Bemerkenswerte Unterschiede wurden zwischen IBZ und Fidaxomicin (FDX) beobachtet, was diese beiden Anti-CDI-Antibiotika in zukünftigen Studien möglicherweise unterscheidet. IBZ bereitet sich darauf vor, in internationale Phase-3-Studien zur Behandlung von CDI überzugehen und hat die FDA-QIDP-, Fast-Track- und EMA-SME-Auszeichnungen erhalten.
- First-ever head-to-head comparison shows IBZ has more selective antibacterial activity
- IBZ demonstrates less microbiome disruption vs. vancomycin and metronidazole
- IBZ increases beneficial bacteria (Bifidobacteria) populations
- Advancing to Phase 3 clinical trials
- Has FDA Fast-Track and QIDP designations
- None.
Insights
Acurx Pharmaceuticals' newly published research represents a significant milestone in the development of ibezapolstat (IBZ), their lead antibiotic for C. difficile infection (CDI). This first-ever head-to-head comparison against other CDI antibiotics provides compelling differentiation data that strengthens IBZ's competitive positioning.
The study demonstrates that IBZ causes less disruption to gut microbiome diversity compared to vancomycin and metronidazole, which aligns with their earlier Phase 2 clinical findings. Importantly, IBZ showed a distinct microbiome profile from fidaxomicin, its nearest competitor, including potentially beneficial increases in Actinomycetota bacteria.
This research establishes a scientific foundation for IBZ's potential competitive advantages as the company prepares for international Phase 3 trials. With both FDA QIDP and Fast-Track Designation already secured, IBZ has regulatory momentum that could accelerate its path to market.
For a micro-cap biotech with
This publication represents important scientific validation for Acurx's ibezapolstat (IBZ) through a sophisticated humanized mouse model. The data reveals IBZ's microbiome-sparing effects are mechanistically different from all current CDI treatments, including fidaxomicin, which is considered the current gold standard.
The specific finding that IBZ increases Actinomycetota bacteria (including Bifidobacteria) is particularly significant from a clinical perspective. These beneficial bacteria are associated with reduced CDI recurrence rates, which addresses one of the most challenging aspects of CDI treatment where
The study's funding by multiple NIH institutes (NIAID, NCI, NCATS) alongside Acurx provides independent credibility to these findings. This external validation differentiates this research from typical company-sponsored studies.
As IBZ advances toward Phase 3 trials, these microbiome findings will likely influence trial design to include endpoints measuring recurrence rates and microbiome restoration - factors that could potentially demonstrate superiority over existing treatments and support premium pricing upon approval.
The combination of these differentiated microbiome effects with IBZ's novel mechanism of action (DNA polymerase IIIC inhibition) creates a compelling scientific narrative that addresses both efficacy and recurrence concerns in CDI treatment, which could translate to significant market advantage if confirmed in Phase 3 studies.
- First ever head-to-head comparison of gut microbiome changes associated with ibezapolstat (IBZ) to other anti-CDI antibiotics in a germ-free mouse model
- Changes in alpha and beta microbiome diversities following IBZ treatment were less pronounced compared to those observed in vancomycin (VAN)-or metronidazole (MET)-treated groups, complementing prior Phase 2 clinical findings showing IBZ's more selective antibacterial activity
- Notable differences were observed between the microbiome of IBZ- and fidaxomicin (FDX)-treated groups, which may allow for differentiation of these two anti-CDI antibiotics in future studies
- Results establish IBZ differentiating effects on the gut microbiome, indicating a more selective spectrum of microbiome alteration compared to broader-spectrum antibiotics like VAN and MET and a narrower spectrum of microbiome alteration compared to FDX
- Preparation continues to advance IBZ into international Ph3 clinical trials for treatment of CDI
- IBZ has previously been granted FDA QIDP and Fast-Track Designation and has received SME (Small and Medium-sized Enterprise) designation by the EMA
According to co-author Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of
Acurx's Executive Chairman, Bob DeLuccia, stated: "These results of this first ever direct comparison of the gut microbiome effects of ibezapolstat in a validated humanized mouse model set the stage for potential competitive advantage of IBZ over all commonly used anti-CDI antibiotics, including fidaxomicin". He added: "These data also serve as a foundation upon which to build future planned preclinical and clinical studies at the appropriate time to further clarify ibezapolstat's favorable effect on the microbiome known to confer health benefits to patients with CDI."
This study was a head-to-head comparison of intestinal microbiome effects of IBZ with other CDI antibiotics and has not been done previously in non-clinical, in vivo models. The purpose of this study was to compare gut microbiome changes associated with IBZ to other anti-CDI antibiotics in groups of germ-free mice. Changes in alpha and beta microbiome diversities following IBZ treatment were less pronounced compared to those observed in VAN- or MET-treated groups. By the end of therapy, IBZ increased the relative abundance of Bacteroidota and Actinomycetota phyla. In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity, a positive outcome, compared to VAN and MET. This analysis places IBZ in a similar category of microbiome disruption as FDX with notable favorable differences of IBZ over FDX and indicating a narrower spectrum of microbiome alteration compared to broader-spectrum agents like VAN and MET. However, notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies, such as increased proportion of Actinomycetota bacteria which include Bifidobacteria and other species known to confer human health benefits.
THE PUBLICATION IS ON OUR WEBSITE: www.acurxpharma.com
About the AAC Journal:
Antimicrobial Agents and Chemotherapy (AAC) is an interdisciplinary journal devoted to the dissemination of knowledge relating to all aspects of antimicrobial and antiparasitic agents and chemotherapy. Generally, any report involving studies on or with antimicrobial, antiviral (including antiretroviral), or antiparasitic agents is within the purview of AAC. Studies involving animal models, pharmacological characterization, and clinical trials are appropriate for consideration.
Acurx previously announced that it had received positive regulatory guidance from the EMA during its Scientific Advice Procedure which confirmed that the clinical, non-clinical and CMC (Chemistry Manufacturing and Controls) information package submitted to EMA supports advancement of the ibezapolstat Phase 3 program and if the Phase 3 program is successful, supports the submission of a Marketing Authorization Application (MAA) for regulatory approval in Europe. The information package submitted to EMA by the Company to which agreement has been reached with EMA included details on Acurx's two planned international Phase 3 clinical trials, 1:1 randomized (designed as non-inferiority vs vancomycin), primary and secondary endpoints, sample size, statistical analysis plan and the overall registration safety database. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program.
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 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
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 importantActinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of
new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.
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 U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, New England Journal of Medicine). Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between
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
View original content:https://www.prnewswire.com/news-releases/acurx-announces-publication-of-nonclinical-in-vivo-data-differentiating-ibezapolstats-gut-microbiome-effects-from-other-anti-cdi-antibiotics-302386442.html
SOURCE Acurx Pharmaceuticals, Inc.
FAQ
What are the key findings of Acurx's (ACXP) ibezapolstat microbiome study?
How does ibezapolstat (ACXP) compare to fidaxomicin in treating C. difficile?
What is the current development stage of ACXP's ibezapolstat?
What regulatory designations has ACXP's ibezapolstat received?
