SAVE THE DATES to listen in to the leading topic expert presentations
shared on January 15, 2021, at the Patient, Family, Caregiver Symposium:
Beginning Tuesday, March 9 from 1:00 p.m. – 2:00 p.m. EST following through on
March 16, March 23, and March 30.
A Symposium specifically developed for Patients Diagnosed With a C. diff. Infection, Being Treated For a Clostridioides diffiicile infection, Recovering From a Clostridioides difficile Infection and Recurrences with Family Members and Caregivers.
The Patient & Family C. diff. Symposium was a gathering of healthcare professionals, keynote speakers, health advocates, practitioners, educators, thought leaders, and patients who are transforming the patient experience and changing the way people experience C. diff. infections worldwide.
Unlike other conferences on this topic, patients will share their C. diff. infection journeys, providing a real-world perspective on patient experience. Our attendees will learn more from this virtual-online symposium and gain knowledge on important topics that will better aid their care and recovery through tools and strategies delivered by keynote speakers.
The Symposium followed the C Diff Foundation Mission statement – Educating and Advocating for the prevention, treatments, clinical trials, diagnostics, and environmental safety of Clostridioides difficile (C. diff.) infections worldwide.
Keynote speakers presented up-to-date data to expand on the existing knowledge and provide important information focused on, yet not limited to, a Clostridioides difficile infection (also known as C. diff., C. difficile, CDAD, CDI) ……
Clinical trials and studies
Introduction to Microbiome Research and Studies
Fecal Microbiota Restoration and Transplants
We hope you enjoy the broadcasts!
Program Chair: Paul Feuerstadt, MD, FACG
Barbara McGovern, MD “Treatment of recurrent C. difficile infection with SER-109, an investigational microbiome drug.”
Paul Feuerstadt, MD ” C. diff. Overview – What is a C. diff. Infection?”
MGB Biopharma, a biopharmaceutical company developing MGB-BP-3, a novel antibacterial, for the treatment of Clostridioides difficile (CDI), today announces the successful completion of its End-of-Phase 2 (EOP2) meeting with the US Food and Drug Administration (FDA), an important milestone for the company and its lead product.
The EOP2 Meeting is a formal step at which companies seek confirmation that their product is considered safe to proceed to broader clinical studies and to explore any additional studies that may be required before entering into Phase 3.
At the meeting, the US FDA confirmed that the design and the endpoints of our two prospective Phase 3 studies were appropriate. The Phase 3 studies, which are expected to recruit approximately 900 patients, will include the superiority of MGB-BP-3 against vancomycin in the critical measure of sustained clinical response as one of their endpoints.
Dr Miroslav Ravic, CEO of MGB Biopharma, said, “The successful completion of the End-of-Phase 2 meeting with the FDA marks the culmination of solid scientific and clinical endeavor by the Company. The positive Phase 2 data showed that MGB-BP-3 provides high rates of Sustained Cure from CDI, a devastating disease. We are very pleased with the guidance received from the FDA on key elements of the Phase 3 program that will support the submission of a New Drug Application (NDA).
“The global pandemic caused by COVID-19 has highlighted the importance of being adequately prepared for infectious diseases. CDI’s ongoing high mortality reminds us that this is a disease with a significant unmet medical need for which new treatments are urgently required. MGB-BP-3, with its unique mode of action, is perfectly positioned to meet the need and provide confidence to patients and clinicians that more effective treatments are just round the corner.”
Professor Thomas Louie, clinical professor at the Cumming School of Medicine at the University of Alberta, Calgary (Canada) and Principal Investigator said, “I am most pleased to have contributed to the success of the Phase 2 clinical study of MGB-BP-3. There is a real need for new agents to address CDI and it is gratifying to see this agent progressing onto its next phase of the study. CDI represents a major burden to the Canadian and US healthcare systems. A novel antibiotic that is able to kill this deadly pathogen before it is able to sporulate offers hope to patients and their families who suffer the pain and misery caused by this disease.”
MGB Biopharma is considering strategic options for the business and has engaged JMP Securities as its exclusive financial advisor.
MGB-BP-3 is a novel antibiotic that belongs to the Minor Groove Binder group, discovered at the University of Strathclyde, with a unique rapid bactericidal activity against Clostridioides difficile (CDI), a feature shared by no other treatment available. A recently completed Phase 2 clinical study in 33 CDI patients using three sequential ascending doses of MGB-BP-3 showed a high initial average cure of 94% in all dosages, a high average sustained cure of 95% in the 2 lower dosages, and preservation of the gut microbiota with the lower dosages. There were correspondingly low recurrence rates of less than 5% for the first two doses. MGB-BP-3 was shown to be safe and well-tolerated with no serious adverse events in either of Phase 1 or 2 clinical studies.
CDI is a serious and life-threatening infection of the large intestine and is the most frequent cause of diarrhea in hospitals and care homes. In the US alone, there are almost half a million cases every year associated with around 30,000 deaths; three people die of uncontrolled CDI each hour. CDI has been recognized as an urgent threat pathogen by the Centers for Disease Control and Prevention (CDC) in the US and is a common consequence of antibiotic treatment in hospitalized patients.
About MGB Biopharma
MGB Biopharma is a clinical-stage company developing a novel class of anti-infectives. Its lead candidate, MGB-BP-3, is an antibacterial that is active against a broad range of important multi-resistant and susceptible Gram-positive pathogens. The Company is developing an oral formulation of MGB-BP-3 for the treatment of Clostridioides difficile Infection (CDI).
In addition to its C. difficile programme, MGB Biopharma has a pipeline of early preclinical compounds against Gram-positive, Gram-negative, anti-fungal, anti-viral and anti-parasitic pathogens.
MGB Biopharma acquired rights to the proprietary minor groove binder (MGB) platform, developed at the University of Strathclyde, Glasgow, with exclusive worldwide licensing rights for all anti-infective fields. This platform provides an opportunity to develop various compounds with a completely new mode of action that are distinct from the antimicrobial drugs used in clinical practice today. As a result, many MGB-based drugs could have the potential to offer significant advantages over existing anti-infectives.
The Company, founded in 2010 and headquartered in Glasgow, Scotland, is backed by Scottish investors including Archangel Investors Limited, Barwell, TRICAPITAL, Syndicate Room, and the Scottish Investment Bank, Scottish Enterprise. The company also received significant support for its clinical programme from Innovate UK.
For example, new data published in The New England Journal of Medicine underscore the shortcomings of advances in testing technology, suggested Sahil Khanna, MBBS, an associate professor of medicine at Mayo Clinic College of Medicine and Science, in Rochester, Minn. (2020;382:1320-1330).
At first glance, the study, which used data from 10 sites nationwide to derive a national estimate of the incidence of CDI, reported a relatively unchanged rate of the disease over a six-year period: 476,400 cases in 2011 and 462,100 cases in 2017. However, Dr. Khanna noted that after adjusting for the increasing use of nucleic acid amplification testing (NAAT), the researchers concluded that the incidence of CDI had actually decreased by 24% during the study period, including a 36% drop in healthcare-acquired CDI cases.
The study highlights a problem with NAAT, according to Khanna.
“NAAT is approximately 95% sensitive in detecting the C. difficile gene, but it cannot determine if the gene is active and toxin-producing, so it has the potential for overdiagnosis and for producing clinical false positives,” he explained. “Because of this, it’s important that we interpret NAAT results in the context of patient symptoms.”
Clinicians must be selective when deciding which patients should be tested, he said, only using it in patients who have acute diarrhea with no obvious alternative explanation, and who have the risk factors for CDI. These include older age, longer hospitalization, immunosuppression, use of antibiotics, gastric acid-suppressing agents, gastrointestinal surgery, manipulation of the gastrointestinal tract, and tube feeding.
“Patients not experiencing an active infection can be colonized with C. difficile, in which case there is a risk of a clinical false positives and unnecessary treatment,” Khanna emphasized.
An alternative testing approach now recommended by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) is the use of a multistep algorithm including glutamate dehydrogenase (GDH) to identify pathogenic bacteria and enzyme immunoassay (EIA) to detect C. difficile toxin (Clin Infect Dis 2018;66:e1-e48). NAAT should be reserved for instances in which results from GDH and EIA are inconclusive, the guidelines recommend.
“Unfortunately, NAAT remains the most commonly used test method,” Khanna said, adding that laboratories are increasingly adopting a two-step protocol of GDH and EIA.
Recurrent CDI mostly occurs in people:65 and older who take antibiotics and receive medical care
staying in hospitals and nursing homes for a long time with weakened immune systems
The treatment landscape for CDI also has changed over the past few years, noted Kim Ly, PharmD, a clinical pharmacy specialist in critical care and infectious diseases at Sunrise Hospital and Medical Center, in Las Vegas. Bezlotoxumab (Zinplava, Merck), a monoclonal antibody, is now approved for combination treatment of toxin B–producing CDI, along with an established antibiotic. Additionally, metronidazole, while still approved for the treatment of CDI, is no longer recommended by IDSA/SHEA as a first-line agent for primary CDI in adults.
“For severe initial episodes of CDI, oral vancomycin and fidaxomicin [Dificid, Merck] are now the preferred agents, and metronidazole is only recommended for nonsevere initial episodes when patients are unable to be treated with oral vancomycin or fidaxomicin,” Kim explained.
For a first recurrence of CDI, the IDSA/SHEA guidelines recommend administering oral vancomycin as a tapered and pulsed regimen or fidaxomicin, rather than a standard 10-day course of vancomycin. For subsequent recurrences, clinicians can use the same regimen, with the addition of a standard course of oral vancomycin followed by rifaximin or fecal microbiota transplantation (FMT).
Metronidazole comes into play again in the management of fulminant CDI, Ly noted.
“The IDSA/SHEA guidelines recommend treating this with oral or rectal vancomycin 500 mg four times daily along with intravenous metronidazole,” she explained.
Given that antibiotic-induced microbiota disruption “is far and away the number one precipitant for getting recurrent CDI,” selecting the CDI treatment with the least impact on the microbiota is important, said former IDSA president Cynthia Sears, MD, a professor in the Department of Medicine, Division of Infectious Diseases, at the Johns Hopkins University School of Medicine, in Baltimore.
“Vancomycin is the most commonly used therapy for CDI and its recurrences, but it decreases intestinal diversity and so impedes the recovery of the normal microbiota after CDI, setting the stage for CDI recurrence,” Sears said. “We have learned that vancomycin hits the colon with full force when taken orally because it is not absorbed, and it has off-target effects on lots of anaerobic bacteria that are essential to intestinal resistance of CDI.”
Fidaxomicin has less of an effect on the microbiota and has been shown to sometimes decrease the risk for CDI recurrence when compared with vancomycin (N Engl J Med 2011;364:422-431), but it can be expensive, she said.
Fecal Microbiota Transplantation
FMT is a less expensive, highly effective treatment that has received increasingly widespread attention, specifically for the management of recurrent CDI. Despite the enthusiasm surrounding the treatment, Sears expressed significant reservations about employing it.
“While there’s no question that FMT benefits patients with recurrent CDI, I feel we don’t yet have a quality-controlled product that we know is safe as well as being effective,” she said.
Sears pointed to two recent FDA safety alerts that warned of the harm that FMT can cause. The first, from 2019, reported that stool from a single donor had not been thoroughly screened before FMT and contained extended-spectrum ss-lactamase–producing Escherichia coli. The specimen had been used in separate FMTs for two immunocompromised patients, leading to infection with the pathogen and death in one case.
In another FDA safety alert from earlier this year, the organization said a stool bank specimen that had undergone comprehensive screening nevertheless contained enteropathogenic E. coli and Shiga toxin-producing E. coli. Transfer of the stool for the treatment of recurrent CDI resulted in one nonfatal infection and one death.
“Stool banks try very hard to be sure their specimens are free of disease-causing microbes, but if you have very low-level colonization, molecular diagnostics can miss this,” Sears said. More recently, she noted, the FDA has also raised concerns about the possibility of transferring SARS-CoV-2 through FMT, given that the virus can be present in the stool of infected individuals.
What would a safer and equally effective microbiota-based treatment look like? According to Sears, while microbial diversity seems to be protective against recurrent CDI, there are suggestions that the administration of specific strains may be able to treat CDI and can be produced under the same strict quality control manufacturing processes as other FDA-approved drugs. One study published in 2015 using human and mouse samples found that colonization with Clostridium scindens, a strain of Firmicutes, increased resistance to CDI (Nature 2015;517:205-208). Many microbiota-based therapeutics are in the research pipeline as well.
“I am optimistic that we will see something emerge that’s safer and still as effective as FMT for patients, whether it’s an orally or rectally administered product,” Sears said.
Seres’s success with an industrially made bacterial mix in phase 3 trials against Clostridium difficile infection promises an alternative to fecal microbial transplantation in clinical practice.
The August announcement of positive data from Seres Therapeutics’ phase 3 trial to prevent recurrent Clostridium difficile infections renewed hopes that purified, defined mixtures of bacteria can treat such infections as effectively as — and presumably more safely than — fecal microbial transplantation (FMT). Several other companies have now also shown favorable late-stage trial data in ‘C. diff.’ using customized stool-derived cocktails. Along with Seres, they are teeing up clinical studies of these compounds in a variety of diseases.
……..Two other companies, Rebiotix, and Vedanta Biosciences are pursuing microbe-based drugs to stop C. diff infection recurrences, and both are in late-stage development. Rebiotix is running a pivotal phase 3 study of its commercially prepared FMT in enema form. Vedanta Biosciences is expecting a readout of its phase 2 trial of VE303, which, unlike the other three drug candidates, is a defined consortium of eight types of cultured, clonal commensal bacteria strains.
– Ibezapolstat is the first of an entirely new class of antibiotics with a novel mechanism of action, a DNA polymerase IIIC inhibitor, to enter clinical efficacy trials
– 10 of 10 patients enrolled in the Ph2A trial met the study’s primary and secondary efficacy
– No C. difficile was detected in any of the 65 fecal samples tested by Day 3 of treatment and thereafter
– Compelling evidence of efficacy allows early termination of Segment 2A and advancement to Segment 2B
– C. difficile bacteria remain on CDC Urgent Threat list, highlighting the need for new CDI treatments
– Ibezapolstat is FDA QIDP and Fast Track Designated for priority review
Acurx Pharmaceuticals, LLC, a privately held, clinical-stage biopharmaceutical company developing an entirely new class of antibiotics for difficult-to-treat bacterial infections, announced today (November 5, 2020) that all 10 patients (100%) with mild-to-moderate CDI enrolled in this Ph2A open-label clinical trial met the study’s primary and secondary efficacy endpoints following treatment with orally administered ibezapolstat given 450 mg twice daily for 10 days. FDA has granted Qualified Infectious Disease Product (QIDP) designation and Fast-Track status to ibezapolstat for patients with CDI.
In this Phase 2 clinical trial, Segment 2A was designed to enroll up to 20 patients with a data review planned by a Trial Oversight Committee after 10 patients completed the trial. All 10 patients enrolled in the trial met the study’s primary and secondary efficacy endpoints of Clinical Cure at end of treatment and Sustained Clinical Cure of no recurrence of CDI at the 28-day follow-up visit. Ibezapolstat was well-tolerated, with no serious adverse events (SAEs) reported in the trial. Based on these successful treatment results, and in consultation with the Company’s medical advisors, the Company has terminated enrollment in Segment 2A early and will advance to Segment 2B. These results also represent the first-ever clinical validation of DNA polymerase IIIC as a therapeutically relevant antibacterial target.
Dr. Kevin Garey, Professor and Chair, University of Houston College of Pharmacy and the Principal Investigator for the microbiome aspects of the trial stated, “Data from my laboratory confirm that ibezapolstat eradicated C. difficile in all fecal samples tested by Day 3 of treatment in this patient population with mild or moderate CDI. Our ongoing work will characterize the effects of ibezapolstat on the intestinal microbiome in these CDI patients. A strength of this development program will be the ability to compare the microbiome results in CDI patients to our prior favorable effects relative to vancomycin previously demonstrated in the Phase 1 healthy volunteer trial.”
Stuart Johnson, MD, Professor of Medicine at Loyola University, a CDI expert and an Acurx Scientific Advisory Board (SAB) member, noted, “After reviewing Segment 2A , the SAB is encouraged by the promising results and fully support early termination and advancement to the Ph2B Segment with the next enrolled patient. The SAB looks forward to successful results from Segment 2B that could pave the way for an important new antibiotic class for the treatment of CDI which remains an area of clear medical need.”
These data will be presented at the 8th Annual International C. diff. Virtual Conference and Virtual Health Expo on November 14, 2020,https://cdiff2020.comwhich coincides with the US Centers for Disease Control and Prevention (CDC) declaration of November as Clostridioides difficile Awareness Month.
Robert J. DeLuccia, Co-Founder & Managing Partner of Acurx, stated, “We are very excited by these excellent results allowing early termination of our Phase 2A Segment at 10 patients. We are looking forward to starting our Phase 2B Segment early next year with expectation for completion by the end of next year”. He further stated, “since ibezapolstat is the first DNA polymerase IIIC inhibitor to advance into clinical trials, this achieves the first human validation of our bacterial target and will enable further development of our pipeline of novel oral and I.V. antibiotics with the same bacterial target and mechanism of action. Our new compounds are in pre-clinical development to treat other Gram-positive life-threatening infections in skin/skin structure, community-acquired pneumonia, bone & joint, and bacteremia. The spectrum of activity of Acurx’s DNA pol IIIC inhibitors includes pathogens resistant to currently available antibiotics and classified as priority pathogens by the WHO, CDC, and FDA, all of whom emphasize the need for new classes of antibiotics to prepare for the next global infectious disease pandemic, antimicrobial resistance.”
About the Phase 2 Clinical Trial. In Segment 2A of this trial, 10 subjects with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally for 10 days and evaluated for clinical cure. All cured subjects were followed for a sustained clinical cure at 28 ± 2 days. In Segment 2B, approximately 64 additional subjects with CDI will be enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours for 10 days and will be followed for 28 ± 2 days for recurrence. The two treatments will be identical in appearance, dosing times, and the number of capsules administered to maintain the blind. Subjects in both segments will be evaluated for clinical and sustained clinical cure, safety, and tolerability. All subjects in both segments will have stool samples tested for microbiome profiles. Additional information about the trial, including eligibility criteria, can be found at www.clinicaltrials.gov (Study identifier: NCT04247542).
About Clostridioides Difficile Infection (CDI). Clostridioides (formerly Clostridium)difficile, also known as C. difficile or C. diff, is one of the most common causes of healthcare-associated infections in U.S. hospitals (Lessa, et al, 2015, New England Journal of Medicine).Recent estimates suggest C. difficile approaches 500,000 infections annually in the United States and are associated with approximately 20,000 deaths. (Guh, 2020, New England Journal of Medicine). Based on internal estimates including a recurrence rate of approximately 20%, we believe the annual incidence in the U.S. approaches 600,000.
About the C Diff Foundation: The Company recognizes the month of November as C. Difficile Awareness Month as designated by the US Centers for Disease Control and Prevention (CDC) and supports the work of the C Diff Foundation in educating and advocating for the Prevention, Treatments, Clinical Trials, and Environmental Safety of Clostridioides difficile (C.difficile) Infections worldwide. https://cdifffoundation.org/. The C Diff Foundation recently announced the release of the C diff and You app, available from the Apple Store (apple.com) and Google Store (play.google.com). Developed with patients, family members, and caregivers in mind, the app provides information about C. difficile infection prevention, treatments, clinical trials, support, guidelines, environmental safety, and nutrition.
The U.S. Center for Diseases Control 2019 Update on Antimicrobial Resistance. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf CDC reported that more than 2.8 million antibiotic-resistant infections occur in the U.S. each year and more than 35,000 people die as a result, nearly twice as many annual deaths as previously reported by CDC in 2013. These deaths are attributed to antimicrobial-resistant pathogens including Enterococcus (including vancomycin-resistant strains or VRE), Staphylococcus (including methicillin-resistant strains or MRSA), and Streptococcus (including antibiotic-resistant strains), which are the targets of the Company’s antibiotic pipeline currently in preclinical development and also eligible for QIDP and FDA-Fast-Track-Designation for priority review.
About ibezapolstat, FDA QIDP, and Fast Track Designation. In June 2018, FDA granted Qualified Infectious Disease Product (QIDP) designation to ibezapolstat as an oral treatment for patients with CDI. In addition, in January 2019, FDA granted Fast Track designation to ibezapolstat for the oral treatment for patients with CDI.
FDA’s QIDP Designation provides that ibezapolstat will be eligible to benefit from certain incentives for the development of new antibiotics provided under the Generating Antibiotic Incentives Now Act (the GAIN Act). These incentives include Priority Review and eligibility for Fast Track status, the latter of which Acurx has already applied for and been granted by the FDA. Further, if ultimately approved by the FDA, ibezapolstat is eligible for an additional five-year extension of Hatch-Waxman marketing exclusivity.
FDA Fast Track Designation is a process designed to facilitate the development and expedite the regulatory pathway of new drugs to treat serious or life-threatening conditions and that fill a high unmet medical need. Ibezapolstat is a novel, first-in-class, orally administered antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors in clinical development by Acurx to treat bacterial infections.
About DNA polymerase IIIC (pol IIIC). Working in scientific collaboration with WuXi AppTec, Acurx has identified additional potential therapeutic candidates to add to its pipeline of DNA pol IIIC inhibitors. Nonclinical research has established the mechanism of action of ibezapolstat as the selective inhibition of the enzyme DNA polpol IIIC, which is required for bacterial replication and pathogenesis. This enzyme is found only in certain Gram-positive bacteria, including C. difficile as well as the pathogens Enterococcus (including vancomycin-resistant strains or VRE), Staphylococcus (including methicillin-resistant strains or MRSA), and Streptococcus (including antibiotic-resistant strains). Accordingly, chemically related molecules with the same mechanism of action as ibezapolstat have the potential to treat a variety of serious systemic Gram-positive infectious diseases.
About Acurx Pharmaceuticals, LLC. Acurx Pharmaceuticals is a privately-held clinical-stage biopharmaceutical company focused on developing new antibiotics for difficult-to-treat infections. Acurx’s approach is to develop antibiotic candidates that target the DNA polymerase IIIC enzyme and its R&D pipeline includes early-stage antibiotic candidates that target other Gram-positive bacteria, including Methicillin-Resistant Staphylococcus aureus (MRSA), Vancomycin-Resistant Enterococcus (VRE), and Penicillin-Resistant Streptococcus pneumoniae (PRSP).
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 United States Food and Drug Administration or equivalent foreign regulatory agencies where approval is sought; whether, if ibezapolstat obtains approval, it will be successfully distributed and marketed; and other factors. In addition, the forward-looking statements included in this press release represent our views as of November 5, 2020. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so.
Investor Contact: Acurx Pharmaceuticals, LLC David P. Luci, Co-Founder & Managing Partner 917-533-1469; firstname.lastname@example.org
SOURCE Acurx Pharmaceuticals, LLC