Acurx Announces New Bile Acid and Microbiome Analyses from Ph2b Trial of Ibezapolstat in CDI Patients Presented at IDWeek Scientific Conference
Acurx Pharmaceuticals (NASDAQ: ACXP) presented new bile acid and microbiome analyses from their Phase 2b trial of ibezapolstat for C. difficile Infection (CDI) at the IDWeek 2024 Conference. The data showed a favorable gut bile acid profile and restoration of beneficial bacteria in ibezapolstat-treated patients, which may contribute to its anti-recurrence effect. Ibezapolstat demonstrated comparable clinical cure rates and safety to vancomycin, with no recurrence in the 5 patients followed for 3 months post-treatment.
Acurx is preparing to advance ibezapolstat into international Phase 3 clinical trials for CDI treatment, following a successful FDA End-of-Phase 2 Meeting. The company plans to submit requests for regulatory guidance in the EU, UK, Japan, and Canada. Ibezapolstat has previously received FDA QIDP and Fast-Track Designation.
Acurx Pharmaceuticals (NASDAQ: ACXP) ha presentato nuove analisi degli acidi biliari e del microbioma dal loro studio di fase 2b su ibezapolstat per l'Infezione da C. difficile (CDI) durante la conferenza IDWeek 2024. I dati hanno mostrato un profilo favorevole degli acidi biliari intestinali e ripristino dei batteri benefici nei pazienti trattati con ibezapolstat, il che potrebbe contribuire al suo effetto anti-recidiva. Ibezapolstat ha dimostrato tassi di guarigione clinica e sicurezza comparabili a quelli della vancomicina, con nessuna recidiva nei 5 pazienti seguiti per 3 mesi dopo il trattamento.
Acurx si sta preparando a far avanzare ibezapolstat in studi clinici internazionali di fase 3 per il trattamento del CDI, dopo un incontro di successo con la FDA alla fine della fase 2. L'azienda prevede di presentare richieste di orientamento normativo nell'UE, nel Regno Unito, in Giappone e in Canada. Ibezapolstat ha precedentemente ricevuto designazione QIDP e Fast-Track dalla FDA.
Acurx Pharmaceuticals (NASDAQ: ACXP) presentó nuevos análisis de ácidos biliares y microbioma de su ensayo de fase 2b de ibezapolstat para la infección por C. difficile (CDI) en la Conferencia IDWeek 2024. Los datos mostraron un perfil favorable de ácidos biliares en el intestino y restauración de bacterias beneficiosas en los pacientes tratados con ibezapolstat, lo que podría contribuir a su efecto anti-recidiva. Ibezapolstat demostró tasas de curación clínica y seguridad comparables a las de la vancomicina, con ninguna recidiva en los 5 pacientes seguidos durante 3 meses después del tratamiento.
Acurx se está preparando para avanzar ibezapolstat a ensayos clínicos internacionales de fase 3 para el tratamiento del CDI, tras una exitosa reunión de final de fase 2 con la FDA. La compañía planea presentar solicitudes de orientación regulatoria en la UE, el Reino Unido, Japón y Canadá. Ibezapolstat recibió anteriormente designación QIDP y Fast-Track de la FDA.
Acurx Pharmaceuticals (NASDAQ: ACXP)는 IDWeek 2024 회의에서 ibezapolstat의 C. difficile 감염(CDI)에 대한 2b상 시험의 새로운 담즙산 및 미생물 분석을 발표했습니다. 데이터는 ibezapolstat으로 치료받은 환자들에게서 유리한 장 담즙산 프로필과 유익한 박테리아의 회복을 보여주었고, 이는 재발 방지 효과에 기여할 수 있습니다. Ibezapolstat은 바니코마이신과 비교 가능한 임상 치료율과 안전성을 보였으며, 치료 후 3개월 동안 추적한 5명의 환자에게서 재발이 없었습니다.
Acurx는 성공적인 FDA 2상 종료 회의 이후 CDI 치료를 위한 국제 3상 임상 시험으로 ibezapolstat을 진행할 준비를 하고 있습니다. 이 회사는 EU, 영국, 일본 및 캐나다에서 규제 안내 요청을 제출할 계획입니다. Ibezapolstat은 이전에 FDA QIDP 및 패스트트랙 지정을 받았습니다.
Acurx Pharmaceuticals (NASDAQ: ACXP) a présenté de nouvelles analyses des acides biliaires et du microbiome lors de l'essai de phase 2b de ibezapolstat pour l'infection à C. difficile (CDI) lors de la conférence IDWeek 2024. Les données ont montré un profil d'acides biliaires intestinal favorable et la restauration des bactéries bénéfiques chez les patients traités par ibezapolstat, ce qui pourrait contribuer à son effet anti-rechute. Ibezapolstat a démontré des taux de guérison clinique et de sécurité comparables à ceux de la vancomycine, sans rechutes chez les 5 patients suivis pendant 3 mois après le traitement.
Acurx se prépare à faire avancer ibezapolstat vers des essais cliniques internationaux de phase 3 pour le traitement de la CDI, à la suite d'une réunion fructueuse avec la FDA à la fin de la phase 2. L'entreprise prévoit de soumettre des demandes d'orientation réglementaire dans l'UE, au Royaume-Uni, au Japon et au Canada. Ibezapolstat a précédemment reçu la délivrance QIDP et Fast-Track de la FDA.
Acurx Pharmaceuticals (NASDAQ: ACXP) präsentierte auf der IDWeek 2024-Konferenz neue Analysen von Gallensäuren und Mikrobiom aus ihrer Phase-2b-Studie zu ibezapolstat zur Behandlung der C. difficile-Infektion (CDI). Die Daten zeigten ein vorteilhaftes gallensäurliches Profil im Darm und die Wiederherstellung von nützlichen Bakterien bei mit ibezapolstat behandelten Patienten, was zu seiner Wirkung gegen Rückfälle beitragen könnte. Ibezapolstat zeigte vergleichbare klinische Heilungsraten und Sicherheit im Vergleich zu Vancomycin, mit keiner Rückkehr bei den 5 Patienten, die 3 Monate nach der Behandlung nachverfolgt wurden.
Acurx bereitet sich darauf vor, ibezapolstat in internationale Phase-3-Studien zur CDI-Behandlung voranzubringen, nach einem erfolgreichen Treffen mit der FDA am Ende der Phase 2. Das Unternehmen plant, Anträge auf regulatorische Leitlinien in der EU, im Vereinigten Königreich, in Japan und Kanada einzureichen. Ibezapolstat erhielt zuvor die QIDP- und Fast-Track-Zulassung von der FDA.
- Ibezapolstat showed comparable clinical cure rates and safety profile to vancomycin in Phase 2b trial
- No recurrence observed in 5 ibezapolstat patients followed for 3 months post-treatment
- Favorable gut bile acid profile and restoration of beneficial bacteria observed in ibezapolstat-treated patients
- Agreement reached with FDA on key elements for Phase 3 clinical trials and NDA filing
- Ibezapolstat has received FDA QIDP and Fast-Track Designation
- None.
Insights
The presentation of new bile acid and microbiome analyses from ibezapolstat's Phase 2b trial at IDWeek 2024 provides valuable insights into the drug's potential efficacy against C. difficile infection (CDI). Key findings include:
- Comparable clinical cure rates to vancomycin
- No recurrence in 5 patients followed for 3 months post-treatment
- Increased proportion of beneficial bacteria in the gut
- Favorable changes in bile acid composition
These results suggest ibezapolstat may have advantages in preventing CDI recurrence, a significant clinical challenge. The preservation of beneficial gut bacteria and favorable bile acid profile could contribute to a reduced risk of recurrence compared to current treatments.
The company's progress towards Phase 3 trials, including FDA agreement on key elements and plans for international regulatory submissions, indicates strong momentum in ibezapolstat's development. With QIDP and Fast-Track designations from the FDA, ibezapolstat appears well-positioned in the regulatory pathway.
For investors, this news suggests positive progress in Acurx's lead candidate, potentially addressing a significant unmet need in CDI treatment. However, as a small-cap company (
This news represents a significant milestone for Acurx Pharmaceuticals (NASDAQ: ACXP), a small-cap biotech with a market capitalization of approximately
Key financial implications include:
- Reduced development risk: FDA agreement on Phase 3 trial design and endpoints decreases regulatory uncertainty.
- Expanded market potential: Plans for international trials in EU, UK, Japan and Canada suggest a global commercialization strategy.
- Potential for partnerships or licensing deals: Strong data may attract interest from larger pharmaceutical companies.
However, investors should consider that as a small-cap biotech, Acurx likely has cash reserves. The company will need significant capital to fund the planned Phase 3 trials, which could lead to dilutive financing rounds. The stock may experience increased volatility as it approaches key clinical and regulatory milestones.
While the news is positive, the company's ability to execute its development plan and eventual commercialization strategy will be important for long-term value creation. Investors should closely monitor cash burn rate, potential financing activities and progress in initiating the Phase 3 program.
- The data presented indicate a favorable gut bile acid profile which may contribute to ibezapostat's beneficial anti-recurrence effect in patients with C. difficile Infection (CDI)
- Ibezapolstat treatment of patients with CDI is associated with the restoration of beneficial bacterial classes in the gut
- 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 to be followed by the
United Kingdom ,Japan andCanada - Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA
Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of
In the Phase 2b clinical trial, ibezapolstat had comparable clinical cure and sustained clinical cure rates and safety profile to vancomycin. Also, 5 of 5 ibezapolstat patients who were followed for 3 months after end of treatment (EOT) experienced no recurrence. Favorable microbiome results were observed in ibezapolsat-treated patients who had increased proportion of Actinobacteriota and beneficial Bacillota. Furthermore, ibezapolstat-treated patients showed decreased concentrations of fecal primary bile acids, and higher ratios of secondary to primary bile acids than vancomycin-treated patients.
According to Dr. Garey: "These exciting results demonstrate two properties of ibezapolstat which may contribute to the anti-recurrence effect. First, the preservation and restoration of beneficial bacterial classes in the gut provide resistance to recolonization by C. difficile. Second, these data, presented for the first time, indicate that these beneficial bacteria known to metabolize primary to secondary bile acids persist in ibezapolstat-treated patients providing another important mechanism to prevent recurrent CDI".
Robert J. DeLuccia, Executive Chairman of Acurx, stated: "This new impressive bile acid and microbiome data compliment and extend our knowledge of ibezapolstat's pharmacologic profile. These results, when added to previous work showing anti-virulence properties, preclinically, give us a high level of confidence that our excellent Phase 2 clinical results will be confirmed in our Phase 3 studies". The scientific poster is available on the Acurx Pharmaceuticals website at 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, to be followed by requests to be submitted in 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 IDSA and IDWeek
The Infectious Diseases Society of America (IDSA) is a community of over 12,000 physicians, scientists and public health experts who specialize in infectious diseases. Our mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases. IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP).
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 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 (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 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
View original content:SOURCE Acurx Pharmaceuticals, Inc.
FAQ
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