Acurx Announces FDA Has Granted an End of Phase 2 Meeting for Ibezapolstat for C. difficile Infection and the European Medicines Agency Granted SME Designation for Ibezapolstat EU Development
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Insights
The progression of ibezapolstat to international Phase 3 clinical trials marks a significant milestone in Acurx Pharmaceuticals' development pipeline, particularly for the treatment of Clostridioides difficile Infection (CDI), a bacterial infection with substantial morbidity and healthcare-associated costs. The End of Phase 2 Meeting with the FDA is a critical juncture, as it will determine the robustness of the Phase 3 development plan, which is pivotal for a New Drug Application (NDA). The FDA's QIDP and Fast-Track Designation previously granted to ibezapolstat underscore the urgency and unmet need in treating CDI, potentially accelerating the regulatory review process.
From a research standpoint, the details of the pre-meeting Briefing Document are crucial as they outline the clinical development plan including pharmacology and microbiology studies. The success of Phase 2 trials and the FDA's acceptance of the meeting request suggest a favorable view of the data presented, although the specifics of these data are not disclosed in the current context. The SME designation by the EMA further highlights the strategic importance of this drug in the European market, offering Acurx financial and regulatory incentives that could facilitate a smoother path to market entry in the EU.
Investors and stakeholders in Acurx Pharmaceuticals may consider the FDA's EOP2 meeting confirmation and the EMA's SME designation as positive indicators of ibezapolstat's market potential. The EOP2 meeting suggests that the FDA sees potential in the drug advancing to the next phase, which could lead to a significant value inflection point upon successful completion of Phase 3 trials. Furthermore, the SME designation in Europe can be seen as a strategic advantage, potentially reducing the time and cost associated with regulatory processes and enhancing the company's ability to compete in the international pharmaceutical market.
It is also pertinent to consider the broader market dynamics, such as the competitive landscape for CDI treatments and the potential market size. The current treatments available for CDI and the clinical need for new antibiotics due to rising antibiotic resistance will influence the market reception of ibezapolstat. Should the drug prove to be effective and gain regulatory approval, it could capture a significant share of the CDI treatment market, which would have a substantial impact on Acurx's financials and stock performance.
The economic implications of advancing a drug like ibezapolstat into Phase 3 trials are multifaceted. On one hand, the direct costs associated with large-scale international clinical trials are considerable and the SME designation by the EMA suggests that Acurx may benefit from reduced financial burden in this regard. On the other hand, the potential market for a successful CDI treatment is significant, given the prevalence of the infection and the economic costs associated with it, including hospital stays and lost productivity.
Investments in research and development (R&D) for antibiotics are often seen as high-risk due to the scientific and regulatory hurdles; however, the support from regulatory bodies such as the FDA and EMA indicates a recognition of the need for new treatments. The economic benefits of bringing a successful antibiotic to market extend beyond the company to the healthcare system as a whole, potentially reducing the long-term costs of treating antibiotic-resistant infections.
- As previously announced, planning is underway with FDA to advance ibezapolstat into international Phase 3 clinical trials for treatment of C. difficile Infection (CDI)
- As anticipated, an End of Phase 2 Meeting (EOP2) with FDA is now confirmed to occur in late April 2024 to finalize the Phase 3 development plan
- Per FDA Guidance, Acurx also announced it has submitted the required pre-meeting Briefing Document to FDA yesterday, February 26, 2024
- 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
- Ibezapolstat has previously received FDA QIDP and Fast-Track Designation
Additionally, the Company was granted SME designation by the European Medicines Agency on February 15, 2024 which allows Acurx to benefit from fee incentives and other support from the EMA for conduct of required clinical trials for ultimate EU Marketing Authorization. The SME designation was established by EMA to promote innovation and the development of new medicinal products by smaller companies. Companies with SME status are eligible to receive financial incentives as well as administrative and regulatory support through national and regional level programs. These benefits include access to dedicated EMA personnel during the clinical development process as well as reductions in fees associated with regulatory procedures such as Scientific Advice, Marketing Authorizations, and inspections.
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "We are very pleased to have our FDA EOP2 Meeting granted which confirms that our Meeting Request information package was acceptable since FDA could deny such a meeting for sponsors if it is premature for the stage of development or because the meeting information package provided is not adequate. He further stated: "Having SME status granted by EMA will allow us to leverage the outcome our EOP2 FDA meeting to seek EMA guidance for requirements of a Marketing Authorization in the EU which is consistent with our plan to conduct international Phase 3 clinical trials."
David P. Luci, President & CEO of Acurx, stated: "We are pleased to have the opportunity to meet with FDA to confirm readiness for, and design of, our Phase 3 program which includes international clinical study sites and to have SME designation, allowing us to benefit from financial incentives and support from the EMA as we aim to ultimately bring ibezapolstat to the global pharmaceutical marketplace. Throughout 2024 we anticipate further regulatory developments internationally to leverage our success with
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 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:SOURCE Acurx Pharmaceuticals, Inc.
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