Acurx Pharmaceuticals Announces Presentation of Ibezapolstat Phase 2 Clinical Trial Results for CDI at Scientific Conference
Acurx Pharmaceuticals (NASDAQ: ACXP) presented results from the ibezapolstat Phase 2 clinical trial for C. difficile Infection (CDI) at the 17th Biennial Congress of the Anaerobe Society of the Americas. The study showed favorable gut microbiome changes, including increased Actinobacteria in treated patients. Results were consistent with earlier studies, demonstrating preservation of beneficial bacteria. Dr. Kevin Garey highlighted the robust microbiome development plan, predicting an anti-recurrence effect of ibezapolstat. The company is preparing for Phase 3 clinical trials following a successful FDA End-of-Phase 2 Meeting, with plans to expand internationally.
- Ibezapolstat demonstrated favorable effects on gut microbiome while curing C. difficile infection
- Successful FDA End-of-Phase 2 Meeting with agreement on key elements for Phase 3 clinical trials
- Preparation for international Phase 3 clinical trials in progress
- Potential competitive advantage due to dual mechanism of action reducing infection recurrence
- None.
Insights
The recent results from Acurx Pharmaceuticals' Phase 2b clinical trial for ibezapolstat, presented at a significant scientific conference, provide compelling new data on its efficacy against C. difficile infections (CDI). One of the standout findings is the favorable impact on the gut microbiome, particularly the increased relative proportion of Actinobacteria and preservation of Firmicute populations. These findings are critical because they suggest that ibezapolstat can treat the infection while also promoting gut health, a dual mechanism that is not commonly seen in antibiotics.
For patients, this could mean a lower recurrence rate of CDI and better overall gut health, addressing two significant issues simultaneously. It's vital to note that the results are consistent with earlier studies, adding to the robustness of the data. This consistency increases confidence in the reliability of ibezapolstat's effects as the drug moves into Phase 3 trials.
Investors should keep an eye on how these microbiome effects are received by the broader medical community, as they could set a new benchmark for antibiotic development, potentially making ibezapolstat a market leader in CDI treatment.
From a financial perspective, the Phase 2b results are pivotal for Acurx Pharmaceuticals. The favorable outcomes related to ibezapolstat reinforce the company's value proposition as it prepares for Phase 3 trials and eventual commercialization. Reaching an agreement with the FDA on the development plan and readiness for Phase 3 trials is a significant milestone. It not only de-risks the project but also positions Acurx for potential accelerated approval pathways.
For retail investors, the news signals a reduced regulatory risk and a clearer path to market, which can translate to increased stock stability and potential appreciation. Moreover, the dual mechanism of action—treating CDI effectively while preserving gut microbiome health—could lead to a larger market penetration and competitive advantage over existing treatments. This positions ibezapolstat as a more comprehensive solution, likely driving higher adoption rates upon approval.
It's essential, however, to remain cautious about the costs associated with ongoing and upcoming trials. While the Phase 3 readiness is a positive sign, the financial burden of such extensive trials could affect Acurx's short-term cash flow and may necessitate additional funding rounds.
- Additional analyses of clinical and microbiological data from the Phase 2b segment show favorable gut microbiome changes including increased relative proportion of Actinobacteria in ibezapolstat-treated patients with C. difficile Infection (CDI)
- Results consistent with those shown in earlier human volunteer studies and Phase 2a studies
- Preservation and increased concentrations of beneficial Firmicute (Bacilotta) phylum known to be involved in bile acid homeostasis and short chain fatty acid metabolism was demonstrated
- Actinobacteria and Bacteroides preservation also confirmed using quantitative analysis
Commenting on Dr. Eubank's presentation, Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of
"The ibezapolstat clinical development plan has included the most robust microbiome development plan ever undertaken with prior analyses predicting an anti-recurrence effect of ibezapolstat in patients with CDI." Dr. Garey further added: "Microbiome results from the Phase 2b trial are helping to validate this approach as a consistent anti-recurrence effect has been seen along with the microbiome effect explaining the underlying mechanism of action. I would anticipate that these analyses will set a new standard for CDI-directed antibiotics and perhaps for antibiotic development, in general."
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "Ibezapolstat continues to demonstrate favorable effects on the gut microbiome while at the same time curing the C. difficile bacterial infection comparable to standard of care antibiotics. As we continue to prepare for initiation of our Phase 3 clinical program, we expect this feature of ibezapolstat's dual mechanism of action to be an important competitive advantage by reducing the recurrence of the infection, as well as improving the health of the gut microbiome."
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 now preparing to submit requests for guidance to initiate clinical trials in the European Union, the
About the Anaerobe Society of the
Founded in 1992, The Anaerobe Society of the
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 and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism.
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.
The completed Phase 2a segment of this trial was an open label cohort of up to 20 subjects from study centers in
In the now completed Phase 2b trial segment, 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
The Phase 2b clinical trial segment was discontinued due to success. The Company made this decision in consultation with its medical and scientific advisors and statisticians based on observed aggregate blinded data and other factors, including the cost to maintain clinical trial sites and slow enrollment due to COVID-19 and its aftermath. The Company had determined that the trial performed as anticipated for both treatments, ibezapolstat and the control antibiotic vancomycin (a standard of care to treat patients with CDI), with high rates of clinical cure observed across the trial.
The Phase 2b trial was originally designed to be a non-inferiority (NI) trial and later amended to include an interim efficacy analysis with review by an Independent Data Monitoring Committee (IDMC). The decision to end the trial early based on blinded clinical observations obviated the need for an interim analysis, IDMC review, and NI assessment. The Company determined, in consultation with its clinical and statistical experts, that presenting clinical cure rates for the primary efficacy endpoint is the most appropriate representation for the clinical activity of ibezapolstat in treating CDI.
In the Phase 2 clinical trial, the Company will also evaluate 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+ 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, 2022, 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-pharmaceuticals-announces-presentation-of-ibezapolstat-phase-2-clinical-trial-results-for-cdi-at-scientific-conference-302195596.html
SOURCE Acurx Pharmaceuticals, Inc.
FAQ
What were the key findings of Acurx Pharmaceuticals' ibezapolstat Phase 2 clinical trial for CDI?
What is the next step for Acurx Pharmaceuticals (ACXP) in developing ibezapolstat?
How does ibezapolstat's mechanism of action potentially give it a competitive advantage?
When and where were the results of Acurx Pharmaceuticals' (ACXP) ibezapolstat Phase 2 trial presented?
