Acurx Announces Successful FDA End-of-Phase 2 Meeting and Phase 3 Readiness for Ibezapolstat in the Treatment of C. difficile Infection
Acurx Pharmaceuticals (NASDAQ: ACXP) has announced the successful conclusion of an FDA End-of-Phase 2 meeting, allowing the advancement of ibezapolstat for the treatment of C. difficile Infection (CDI) to Phase 3 clinical trials. The FDA agreed on key trial elements including protocol design and patient population. The trials will involve 450 subjects using a Modified Intent-To-Treat (mITT) population. Ibezapolstat has received FDA's QIDP and Fast-Track Designation and recently obtained SME designation from the European Medicines Agency, enabling fee incentives for EU Marketing Authorization. Plans include initiating trials in the EU, UK, Japan, and Canada.
- Successful FDA End-of-Phase 2 meeting completion.
- Agreement on Phase 3 trial design and patient population.
- FDA's QIDP and Fast-Track Designation for ibezapolstat.
- SME designation by European Medicines Agency, offering fee incentives.
- Preparation for Phase 3 trials in multiple regions including the EU, UK, Japan, and Canada.
- None reported in the PR.
Insights
The announcement regarding Acurx Pharmaceuticals' successful FDA End-of-Phase 2 meeting is significant from a financial perspective. The green light to advance ibezapolstat into Phase 3 trials is a major milestone and often a pivotal moment for pharmaceutical companies. The completion of Phase 2 and the alignment with FDA on the Phase 3 protocol can reduce regulatory uncertainty, a key risk factor for investors. The progression to Phase 3 typically signals that the drug candidate has shown sufficient efficacy and safety in earlier trials and the company is now poised to initiate larger, more expensive trials required for market approval.
This development could result in positive investor sentiment, potentially boosting the stock price in the short term. However, investors should consider the substantial financial investments needed for Phase 3 trials, which might lead to increased cash burn and possibly require additional funding rounds or partnerships. It's worth noting the SME designation by the EMA, which provides financial incentives and support, mitigating some cost concerns for international trials.
Overall, while this news is encouraging and reflects progress, investors should remain vigilant about the financial health and funding strategies of Acurx as they move toward Phase 3 and eventual market entry.
The transition of ibezapolstat into Phase 3 clinical trials is a important step for Acurx Pharmaceuticals. From a clinical standpoint, Phase 3 trials are designed to confirm efficacy and monitor adverse reactions in a larger patient cohort - in this case, 450 subjects with C. difficile Infection (CDI). The choice of a non-inferiority trial comparing ibezapolstat to vancomycin is strategic, aiming to demonstrate that ibezapolstat is at least as effective as the current standard of care. This trial will also assess the potential of ibezapolstat to reduce CDI recurrence, an important outcome given the high recurrence rate associated with CDI.
The prior receipt of FDA QIDP (Qualified Infectious Disease Product) and Fast-Track designations underscores the importance and potential of ibezapolstat in addressing an unmet medical need. This accelerates the review process and provides additional regulatory support.
For retail investors, understanding the trial design and its implications is critical. The Modified Intent-To-Treat (mITT) population alignment with EMA requirements indicates a robust trial design, likely increasing the chances of regulatory approval if the results are positive. However, the long duration of Phase 3 trials means results may not be immediately forthcoming, requiring patience from investors.
Acurx Pharmaceuticals’ news about advancing ibezapolstat into Phase 3 trials offers a meaningful context for market prospects. The international scope of the Phase 3 clinical trials, including plans to seek guidance for trials in the EU, UK, Japan and Canada, illustrates Acurx's ambition to penetrate global markets. This broad geographic strategy can diversify market risks and open multiple revenue streams upon eventual drug approval.
The Small and Medium-sized Enterprise (SME) designation by the EMA is particularly noteworthy. This status not only provides fee reductions but also offers regulatory support, which can facilitate smoother market entry in the EU. This support can be a significant competitive advantage for Acurx, aiding in faster and more cost-effective market penetration.
Investors should recognize the potential for ibezapolstat to become a significant player in the antibiotic market, particularly in treating CDI, a serious and recurring infection. However, market entry is contingent on successful trial outcomes and navigating regulatory approvals in multiple regions. Additionally, competition from existing treatments and other pipeline drugs must be considered in evaluating the market potential and long-term value proposition of Acurx's product.
- Agreement with FDA reached on key elements to move forward with our international Phase 3 clinical trial program
- Agreement also reached with FDA on complete non-clinical and clinical development plan for filing of a New Drug Application for marketing approval
- Planning continues to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI)
- SME (Small and Medium-sized Enterprise) designation has been granted by the EMA (European Medicines Agency), which allows Acurx to benefit from fee incentives and other support from the EMA for EU Marketing Authorization
- Acurx is now preparing to submit requests for 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
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.
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "We are very pleased with the successful outcome of our End of Phase 2 meeting with the FDA and to have reached this important development milestone for our company. We can now proceed with plans to prepare for initiation of the first international Phase 3 trial. He further stated: "We now have a complete roadmap not only for the required components of our phase 3 clinical program, but also what is required for ultimate filing of a New Drug Application to be followed by submissions for Marketing Authorizations in other countries around the world."
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.
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
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 without any emerging safety concerns. Accordingly, an Independent Data Monitoring Committee was not required to perform an interim analysis of this Phase 2b trial data as originally planned. The Company anticipated that this decision would allow the Company to advance this first-in-class, FDA QIDP/Fast Track-designated antibiotic product candidate to Phase 3 clinical trials more expeditiously.
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-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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