Acurx Announces Additional Ibezapolstat Ph2b Results in CDI as well as Anthrax (B. anthracis) Susceptibility to ACX-375 Analogues
Acurx Pharmaceuticals (NASDAQ: ACXP) announced new analyses extending data on ibezapolstat's beneficial effects on the gut microbiome for C. difficile Infection (CDI) treatment. The data showed increased beneficial bacteria, reversing dysbiosis and contributing to CDI anti-recurrence. Ibezapolstat's favorable pharmacokinetics were confirmed with low systemic exposure and high colonic concentrations.
Additionally, certain ACX-375 DNA pol IIIC analogues demonstrated in vitro activity against Anthrax (B. anthracis), including ciprofloxacin-resistant strains. Acurx is planning an Anthrax bioterrorism development program.
The company is preparing to advance ibezapolstat into international Phase 3 clinical trials for CDI treatment and submit requests for regulatory guidance in various countries. Ibezapolstat has previously received FDA QIDP and Fast-Track Designation.
Acurx Pharmaceuticals (NASDAQ: ACXP) ha annunciato nuove analisi che ampliano i dati sugli effetti benefici di ibezapolstat sul microbioma intestinale per il trattamento dell'infezione da C. difficile (CDI). I dati hanno mostrato un aumento dei batteri benefici, invertendo la disbiosi e contribuendo a ridurre le recidive di CDI. Le favorevoli caratteristiche farmacocinetiche di ibezapolstat sono state confermate con basse esposizioni sistemiche e alte concentrazioni nel colon.
Inoltre, alcuni analoghi del DNA pol IIIC di ACX-375 hanno dimostrato attività in vitro contro l'antrace (B. anthracis), incluse le ceppi resistenti alla ciprofloxacina. Acurx sta pianificando un programma di sviluppo per il bioterrorismo dell'antrace.
La società si sta preparando a far avanzare ibezapolstat verso trials clinici internazionali di fase 3 per il trattamento della CDI e a presentare richieste di orientamento normativo in vari paesi. Ibezapolstat ha già ricevuto la designazione FDA QIDP e Fast-Track.
Acurx Pharmaceuticals (NASDAQ: ACXP) anunció nuevos análisis que amplían los datos sobre los efectos beneficiosos de ibezapolstat en el microbioma intestinal para el tratamiento de la infección por C. difficile (CDI). Los datos mostraron un aumento en las bacterias beneficiosas, revirtiendo la disbiosis y contribuyendo a la reducción de la recurrencia de CDI. Se confirmaron las favorables características farmacocinéticas de ibezapolstat con baja exposición sistémica y altas concentraciones en el colon.
Además, ciertos análogos de DNA pol IIIC de ACX-375 demostraron actividad in vitro contra ántrax (B. anthracis), incluidas cepas resistentes a ciprofloxacina. Acurx está planeando un programa de desarrollo para el bioterrorismo del ántrax.
La compañía se está preparando para avanzar a ibezapolstat a ensayos clínicos internacionales de fase 3 para el tratamiento de CDI y presentar solicitudes de orientación regulatoria en varios países. Ibezapolstat ha recibido previamente designación QIDP y Fast-Track por parte de la FDA.
Acurx Pharmaceuticals (NASDAQ: ACXP)는 ibezapolstat의 장내 미생물군에 미치는 유익한 효과에 대한 데이터를 확장하는 새로운 분석을 발표했습니다. C. difficile 감염 (CDI) 치료를 위한 데이터는 유익한 박테리아가 증가하고, 불균형이 역전되어 CDI 재발에 기여함을 보여주었습니다. Ibezapolstat의 유리한 약리학적 특성은 낮은 전신 노출과 높은 결장 농도로 확인되었습니다.
또한 특정 ACX-375 DNA pol IIIC 유사체는 탄저균 (B. anthracis)에 대한 시험관 내 활성을 나타냈으며, 시프로플록사신 내성 균주를 포함합니다. Acurx는 탄저균 생물 테러 개발 프로그램을 계획하고 있습니다.
회사는 ibezapolstat를 국제 3상 임상 시험으로 진행할 준비를 하고 있으며, 여러 국가에서 규제 지침 요청을 제출할 예정입니다. Ibezapolstat는 이전에 FDA QIDP 및 패스트트랙 지정을 받았습니다.
Acurx Pharmaceuticals (NASDAQ: ACXP) a annoncé de nouvelles analyses étendant les données sur les effets bénéfiques d'ibezapolstat sur le microbiome intestinal pour le traitement de l'infection à C. difficile (CDI). Les données ont montré une augmentation des bactéries bénéfiques, inversant la dysbiose et contribuant à la réduction des récurrences de CDI. Les caractéristiques pharmacocinétiques favorables d'ibezapolstat ont été confirmées par une faible exposition systémique et des concentrations coliques élevées.
De plus, certains analogues de l'ADN pol IIIC d'ACX-375 ont montré une activité in vitro contre l'anthrax (B. anthracis), y compris des souches résistantes à la ciprofloxacine. Acurx prévoit un programme de développement sur l'anthrax pour le bioterrorisme.
L'entreprise se prépare à faire avancer ibezapolstat vers des essais cliniques internationaux de phase 3 pour le traitement de la CDI et à soumettre des demandes de conseils réglementaires dans plusieurs pays. Ibezapolstat a précédemment reçu la désignation QIDP et Fast-Track de la FDA.
Acurx Pharmaceuticals (NASDAQ: ACXP) hat neue Analysen veröffentlicht, die die Daten zu den vorteilhaften Wirkungen von ibezapolstat auf das Mikrobiom des Darms zur Behandlung von C. difficile Infektionen (CDI) erweitern. Die Daten zeigten eine Zunahme nützlicher Bakterien, was die Dysbiose umkehrte und zur Verringerung von CDI-Rückfällen beitrug. Die positiven pharmakokinetischen Eigenschaften von ibezapolstat wurden mit einer niedrigen systemischen Exposition und hohen Konzentrationen im Colon bestätigt.
Zusätzlich zeigten bestimmte ACX-375 DNA pol IIIC-Analoga in vitro Aktivität gegen Anthrax (B. anthracis), einschließlich ciprofloxacin-resistenter Stämme. Acurx plant ein Entwicklungsprogramm für Bioterrorismus im Zusammenhang mit Anthrax.
Das Unternehmen bereitet sich darauf vor, ibezapolstat in internationale Phase-3-Studien für die CDI-Behandlung voranzubringen und Anfragen nach regulatorischen Leitlinien in verschiedenen Ländern zu stellen. Ibezapolstat hat zuvor FDA QIDP und Fast-Track-Designation erhalten.
- New analyses show ibezapolstat's beneficial effects on gut microbiome for CDI treatment
- Ibezapolstat demonstrated favorable pharmacokinetics with low systemic exposure and high colonic concentrations
- ACX-375 analogues showed in vitro activity against Anthrax, including ciprofloxacin-resistant strains
- Preparing to advance ibezapolstat into international Phase 3 clinical trials for CDI treatment
- Ibezapolstat has FDA QIDP and Fast-Track Designation
- None.
Insights
This news is highly impactful for Acurx Pharmaceuticals and its lead candidate, ibezapolstat. The additional Phase 2b results strengthen ibezapolstat's potential as a treatment for C. difficile Infection (CDI). Key findings include:
- Beneficial effects on gut microbiome, potentially reducing CDI recurrence
- Favorable pharmacokinetics with low systemic exposure and high colonic concentrations
- Agreement with FDA on Phase 3 trial design and NDA requirements
The company is advancing towards international Phase 3 trials, which is a significant milestone. The potential for ibezapolstat to be superior to vancomycin could be a game-changer in CDI treatment. Additionally, the unexpected finding of a microbiome signature potentially predicting CDI recurrence could lead to improved treatment strategies.
The in vitro activity of ACX-375 analogues against Anthrax, including ciprofloxacin-resistant strains, opens up a new potential market in bioterrorism defense. This diversification could provide additional value and government interest in Acurx's pipeline.
From a financial perspective, this news is highly positive for Acurx Pharmaceuticals (NASDAQ: ACXP). The company is making significant progress with its lead candidate, ibezapolstat, which could translate into substantial market value if successful in Phase 3 trials and eventual commercialization.
Key financial implications include:
- Potential for increased investor interest due to FDA Fast-Track Designation and agreement on Phase 3 trial design
- Expansion into international markets (EU, UK, Japan, Canada) could significantly increase the addressable market
- Diversification into bioterrorism defense with ACX-375 analogues may attract government funding and contracts
With a current market cap of
- New analyses extend data on beneficial effects of ibezapolstat on the gut microbiome
- Confirmed ibezapolstat's favorable pharmacokinetics showing low systemic exposure and high colonic concentrations
- Selected ACX-375 analogues demonstrated in vitro activity against Anthrax (B. anthracis), a Bioterrorism Category A pathogen, including activity against ciprofloxacin resistant Anthrax. Planning is underway for an Anthrax bioterrorism development program
- Preparation continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI)
- Preparing to submit requests for regulatory guidance to initiate clinical trials in the European Union, the
United Kingdom ,Japan andCanada - Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA
Additionally, ibezapolstat's favorable pharmacokinetics properties were confirmed showing mean systemic exposure below 1mcg/mL and fecal concentrations well in excess of the minimal inhibitory concentration (MIC) for C. difficile.
Microbiological testing of certain ACX-375 DNA pol IIIC analogues in independent qualified laboratories, including the University of
The above results were presented at the premier International C. difficile Symposium (ICDS) held in Bled,
According to Dr. Garey: "The microbiome data also show an unexpected finding of a unique microbiome signature in two vancomycin-treated patients in the Ph2b trial who experienced recurrence of CDI. Since these changes were evident and observed early during treatment and then consistently until the end of therapy, they may be predictive of pending CDI recurrence and suggest the need to modify therapy."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These new data add to and reinforce ibezapolstat's emerging overall distinctive product profile, particularly the favorable microbiome-related unexpected findings." He added: "Furthermore, the initial in vitro activity shown against the Bioterrorism Category A pathogen B. anthracis (Anthrax) with some of our earlier-stage compounds included a ciprofloxacin-resistant strain. Selective microbiome effects will be tested with these new compounds as they proceed through development to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other critical gram-positive pathogens in parallel with planning for the Anthrax bioterrorism program. The presentation is available on the Acurx Pharmaceuticals website www.acurxpharma.com
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, 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-Treat (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 C. difficile Symposium (ICDS)
The International C. difficile Symposium (ICDS) is now established as the premier venue for the review of Clostridium difficile research.
The 1st meeting was held in
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. (see https://clinicaltrials.gov/ct2/show/NCT04247542). 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 now completed 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, 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: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).
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) and drug-resistant Streptococcus pneumoniae (DRSP). 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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