Category Archives: Clinical Trials

Acurx Announces that All Patients Demonstrated Clinical and Sustained Cure in Ph2A Open-Label Trial of Ibezapolstat for the Treatment of a C. difficile Infection

 

 

 

 

– 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.com which 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).

For more information, please visit our website at www.acurxpharma.com.

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; davidluci@acurxpharma.com

SOURCE Acurx Pharmaceuticals, LLC

C diff and You app. Available From the Apple Store and Get It On Google

C diff and You

Available From Apple Store and
Get It On Google

Eliminate the hours spent searching for
C. diff. infection information, definitions, and more on the web. Patients, with family members, caregivers,  and friends, are overwhelmed, and absolutely exhausted.

 

 

No one diagnosed with a CDI, and feeling so poorly,  has the time or energy to sit in front of a computer searching, reading, and clicking through pages of information.

Stay connected, stay up-to-date with the C Diff Foundation.

“None of us can do this alone ~ All of us can do this together.”

Download C diff and You today to learn more about
C. diff. (Clostridioides difficile, C. difficile, CDI) infection prevention, treatments, clinical trials, support, environmental safety, and more.

Seres Therapeutics SER-109 Met Phase 3 Primary Endpoint, Positive Results From Pivotal Phase 3 ECOSPOR III Study Evaluating Investigational Oral Microbiome Therapeutic For Recurrent C. difficile Infection

– SER-109 met Phase 3 primary endpoint, showing a highly statistically significant 30.2% absolute reduction in the rate of C. difficile infection recurrence compared to placebo 

– SER-109 was well tolerated, with a safety profile comparable to placebo 

– Efficacy results substantially exceeded FDA regulatory guidance to support BLA filing as a single pivotal trial; Company to meet with the agency to discuss filing for product approval as soon as possible 

 Positive SER-109 Phase 3 data provide validation for Seres’ microbiome therapeutics platform and further development of its pipeline of product candidates 

 Seres Therapeutics, Inc. reported on August 10, 2020, positive topline results from the pivotal Phase 3 ECOSPOR III study evaluating its investigational oral microbiome therapeutic SER-109 for recurrent C. difficile infection (CDI). The study showed that SER-109 administration resulted in a highly statistically significant absolute decrease of 30.2% in the proportion of patients who experienced a recurrence in CDI within eight weeks of administration versus placebo, the study’s primary endpoint. 11.1% of patients administered SER-109 experienced a CDI recurrence, versus 41.3% of placebo patients. The study results were equally compelling when characterized by the alternative metric of sustained clinical response, where 88.9% of patients in the SER-109 arm achieved this objective.

The study’s efficacy results exceeded the statistical threshold previously provided in consultation with the U.S. Food and Drug Administration (FDA) that could allow this single clinical study to fulfill efficacy requirements for a Biologics License Application (BLA). The SER-109 safety results were favorable, with an adverse event profile comparable to placebo.

“We are extremely pleased with these highly clinically meaningful SER-109 Phase 3 study results, greatly exceeding the statistical threshold provided by the FDA. Based on our prior discussions with the FDA, we believe this trial should provide the efficacy basis for submitting an application for product approval. We look forward to meeting with the FDA as soon as possible to discuss the regulatory path forward with the goal of bringing SER-109 to patients as a first-in-class microbiome therapeutic,” said Eric D. Shaff, President and Chief Executive Officer of Seres. “Our results represent the first-ever positive pivotal clinical study results for a targeted microbiome drug candidate. We believe these Phase 3 data provide strong validation for our underlying microbiome therapeutics platform, which has been the scientific basis for the Company, as well as persuasive clinical evidence supporting our other active pipeline programs.”

“We would like to thank all those who participated in this landmark study. Based on these highly positive SER-109 ECOSPOR III results, we believe that this novel microbiome therapeutic candidate could potentially provide a much-needed effective oral treatment option for the approximately 170,000 patients in the U.S. that suffer from recurrent CDI annually,” said Lisa von Moltke, M.D., FCP, Chief Medical Officer of Seres. “Seres applied a data-driven and scientifically rigorous approach to develop SER-109. The proprietary scientific learnings we have obtained continue to drive our overall R&D efforts and the advancement of our other ongoing microbiome therapeutic programs.”

“Recurrent C. difficile infection is a serious disease that devastates patients’ quality of life, and in many severe cases may result in a patient’s death. Today’s treatment options have important shortcomings related to efficacy, safety and route of administration, and novel approaches that target the root causes of the disease are urgently needed. The SER-109 Phase 3 results are highly impressive and represent an exceptional advance in the fight against this disease. I believe that SER-109 has the potential to fundamentally transform the treatment of recurrent C. difficile infection,” said Mark Wilcox, M.D., Professor of Medical Microbiology, University of Leeds.

ECOSPOR III Study Design and Results

The ECOSPOR III study (ClinicalTrials.gov identifier: NCT03183128) is a multicenter, randomized, placebo-controlled study that enrolled 182 patients with multiply recurrent CDI. Patients were randomized 1:1 to receive either SER-109 or placebo, after standard of care antibiotic treatment. SER-109, or placebo, was administered orally for three consecutive days. All patients were required to have a positive C. difficile toxin diagnostic test both at study entry and in the case of suspected recurrence to ensure the selection of individuals with active disease and to confirm the accuracy of the primary endpoint.

The primary efficacy endpoint of ECOSPOR III was the proportion of patients with recurrent CDI at up to eight weeks following administration of SER-109 or placebo. As a secondary endpoint, patients are evaluated for CDI recurrence through 24 weeks post-treatment, and the Company plans to present those results at a future date.

SER-109 met the study’s primary endpoint with a significantly lower recurrence rate of 11.1% in SER-109 patients versus 41.3% in placebo patients at eight weeks; p<0.001 tested at the one-sided 0.25 level. Patients administered SER-109 experienced a 30.2% lower rate of recurrence, on an absolute basis, compared to placebo. The SER-109 treatment arm relative risk was 0.27 (95% CI=0.15 to 0.51) versus placebo. The ECOSPOR III recurrence rates translate into a sustained clinical response rate of 88.9% versus 58.7% with SER-109 and placebo, respectively. The SER-109 Number Needed to Treat (NNT) was approximately 3.

In prior discussions, the FDA communicated that demonstration of a statistically very persuasive efficacy finding in the ECOSPOR III primary endpoint, defined as demonstrating a 95% upper confidence level of relative risk lower than 0.833, could support a BLA submission on the basis of this single study. The results of ECOSPOR III demonstrated a SER-109 relative risk of 0.27 (95% CI=0.15 to 0.51) compared to placebo. As a result, Seres believes that this study should support the efficacy basis for BLA submission. SER-109 has obtained FDA Breakthrough Therapy and Orphan Drug designations.

SER-109 was well tolerated, with no treatment-related serious adverse events (SAEs) observed in the active arm, and an adverse event profile similar to placebo. The overall incidence of patients who experienced AEs during the eight-week study period was similar between SER-109 and placebo arms. The most commonly observed treatment-related AEs were flatulence, abdominal distention and abdominal pain, which were generally mild to moderate in nature, and these were observed at a similar rate in both the SER-109 and placebo arms.

A SER-109 open-label study is ongoing ( clinicaltrials.gov identifier: NCT03183141) at selected clinical sites that participated in the ECOSPOR III study, and the Company may initiate the program at additional clinical sites. The FDA has previously indicated that SER-109 administration to at least 300 patients, consistent with standard FDA guidance, would be required to support BLA submission. The ongoing SER-109 open-label study is continuing to contribute to the SER-109 safety database.

The Company plans to immediately request a Breakthrough Therapy designation meeting with the FDA to discuss the requirements to submit a BLA seeking regulatory approval of SER-109. Given the favorable efficacy and safety results seen in ECOSPOR III, the safety results observed in prior SER-109 clinical studies, and the critical unmet need for a therapeutic option for recurrent CDI patients, the Company plans to discuss with the FDA the safety data requirements for a BLA filing.

Seres continues to advance its commercial readiness for the potential launch of SER-109. In June 2020, Seres appointed Terri Young, Ph.D., R.Ph., as Chief Commercial and Strategy Officer. The Company has been conducting activities to support successful future potential commercialization. Seres believes that the commercial opportunity for SER-109 could be substantial, given the dire need for an effective, safe, oral therapeutic, and the strength of the SER-109 Phase 3 study results.

Conference Call Information

Seres’ management will host a conference call today, August 10, 2020, at 8:30 a.m. ET. To access the conference call, please dial 844-277-9450 (domestic) or 336-525-7139 (international) and reference the conference ID number 3216859. Accompanying slides will be posted on the Seres website ahead of the conference call. To join the live webcast, and to view the accompanying slides, please visit the “Investors and Media” section of the Seres website at www.serestherapeutics.com.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for approximately 21 days.

About SER-109

SER-109 is an investigational, oral, biologically-derived microbiome therapeutic that is designed to reduce recurrence of C. difficile infection (CDI), enabling patients to achieve a sustained clinical response by breaking the vicious cycle of CDI recurrence and restoring the diversity of the gastrointestinal microbiome. SER-109 is a consortium of purified bacterial spores of multiple Firmicute species, manufactured by fractionating targeted bacteria from the stool of healthy human donors with further steps to inactivate potential pathogens. The FDA has granted SER-109 Breakthrough Therapy designation and Orphan Drug designation for the treatment of CDI.

SER-109 is fundamentally distinct from fecal microbiota transplantation (FMT). SER-109 is comprised of a highly-purified consortia of spore-based commensal bacteria and designed to be manufactured in accordance with Good Manufacturing Practice conditions using stringent standards to ensure product quality and consistency. To support product safety, Seres utilizes a unique manufacturing process that inactivates numerous potential pathogens, including species of non-spore bacteria, such as Escherichia coli, and viruses such as SARS-CoV-2.

About C. difficile Infection (CDI) and Current Treatments

C. difficile infection (CDI) is one of the top three most urgent antibiotic-resistant bacterial threats in the U.S., according to the Centers for Disease Control, and is a leading cause of hospital-acquired infection in the U.S. It is responsible for the deaths of approximately 20,000 Americans each year. CDI is associated with debilitating diarrhea, which significantly impacts quality of life in every functional domain. Since the discovery of C. difficile more than four decades ago, vancomycin has been the most commonly used drug for patient management. Current approaches provide only modest improvements in sustained clinical response rates, leaving behind a significant pool of patients with recurrent disease. Unapproved FMT, used in cases that are not responsive to approved drugs, remains poorly characterized clinically and has been associated with serious safety concerns, including the transmission of bacterial pathogens and the potential transmission of viruses such as SARS-CoV-2, the virus that causes COVID-19. The recent quarantine and shipping hold of FMT from a major stool bank highlights the urgent need for an approved effective and safe treatment for recurrent CDI.

About Seres Therapeutics

Seres Therapeutics, Inc., (Nasdaq: MCRB) is a leading microbiome therapeutics platform company developing a novel class of multifunctional bacterial consortia that are designed to functionally interact with host cells and tissues to treat disease. Seres’ SER-109 program achieved the first-ever positive pivotal clinical results for a targeted microbiome drug candidate and has obtained Breakthrough Therapy and Orphan Drug designations from the FDA. The SER-109 program is being advanced for the treatment of recurrent C. difficile infection and has the potential to become a first-in-class FDA-approved microbiome therapeutic. Seres’ SER-287 program has obtained Fast Track and Orphan Drug designations from the FDA and is being evaluated in a Phase 2b study in patients with active mild-to-moderate ulcerative colitis. Seres is developing SER-401 in a Phase 1b study in patients with metastatic melanoma, SER-301 for ulcerative colitis and SER-155 to prevent mortality due to gastrointestinal infections, bacteremia, and graft versus host disease. For more information, please visit www.serestherapeutics.com

SOURCE: Seres Therapeutics

Summit Therapeutics plc Phase 2 Clinical Trial Ridinilazole In Development For the Treatment of C. difficile Infection

Summit Announces Publication of Phase 2 Clinical Analyses of Gut Microbiome Health

July 13, 2020 – Summit Therapeutics plc announced the publication of data from the Phase 2 clinical trial of the company’s precision antibiotic, ridinilazole, in development for the treatment of C. difficile infection (‘CDI’) in the American Journal of Physiology – Gastrointestinal and Liver Physiology. The data published in collaboration with researchers at Tufts University and Tufts Medical Center demonstrated that ridinilazole’s microbiome preservation resulted in a gut environment expected to inhibit the growth of C. difficile. In contrast, vancomycin treatment resulted in a gut environment that may more highly favor the growth of C. difficile. The difference in gut environment could explain the approximately 60% relative reduction in recurrence observed in patients treated with ridinilazole over vancomycin in the Phase 2 trial.

“This is the first scientific article ever to show the effect of antibiotics treating CDI on the bile acid composition in the human gut. In addition, CoDIFy is the first clinical study to highlight the differential effects of antibiotics on bile acids, which are known to create environments that can either promote or protect against CDI,” said Dr. Ventzislav Stefanov, Executive Vice President and President of Discuva. “The protective gut environment observed after ridinilazole treatment, compared to vancomycin, provides a strong rationale for the higher sustained clinical response observed in patients taking ridinilazole in the CoDIFy clinical trial.”

The Phase 2 clinical trial enrolled 100 patients, half of whom received ridinilazole and the other half vancomycin. The publication, “Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids,” was authored by X. Qian, K. Yanagi, A. Kane, N. Alden, M. Lei, D. Snydman, R. Vickers, K. Lee and C. Thorpe. In the published data, there was a higher ratio of pro-C. difficile to anti C.-difficile bile acids at the start of treatment for both ridinilazole- and vancomycin-treated patients. This was expected, as patients who get CDI have perturbed microbiomes. However, during treatment, patients treated with vancomycin showed a further decrease in anti-C. difficile bile acids and had stools dominated by pro-C. difficile bile acids. In contrast, this did not occur in ridinilazole-treated patients. By the end of the study period, ridinilazole-treated patients’ bile acid ratios trended towards a healthy, non-CDI state. These results support the data from the Phase 2 clinical trial, in which patients receiving ridinilazole showed a statistically significant improvement in sustained clinical responses.

SOURCE: https://seekingalpha.com/pr/17929120-summit-announces-publication-of-phase-2-clinical-analyses-of-gut-microbiome-health

Major Article: SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial

SER-109, an Investigational Microbiome Drug to Reduce
Recurrence After Clostridioides difficile Infection: Lessons
Learned From a Phase 2 Trial.

Barbara H. McGovern,1,a,  Christopher B. Ford,1,a , Matthew R. Henn,1,a , Darrell S. Pardi 2
Sahil Khanna,2  Elizabeth L. Hohmann,3  Edward J. O’Brien,1
Christopher A. Desjardins,1, Patricia Bernardo,1, Jennifer R. Wortman,1, Mary-Jane Lombardo,1
Kevin D. Litcofsky,1, Jonathan A. Winkler,1, Christopher W. J. McChalicher,1, Sunny S. Li,1,
Amelia D. Tomlinson,1,Madhumitha Nandakumar,1 David N. Cook1,
Roger J. Pomerantz,1, John G. Auninš,1, and Michele Trucksis1,

1 Seres Therapeutics, Cambridge, Massachusetts, USA, 2 Mayo Clinic, Gastroenterology Division, Rochester, Minnesota, USA, and 3 Massachusetts General Hospital, Infectious Diseases Division, Boston, Massachusetts, USA

Background. Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs.

Methods. In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing.

Safety, C. difficile–positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed.

Results. 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo
(44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years
(45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11–2.81), while the <65 group showed no benefit. Early engraftment of SER-109
was associated with nonrecurrence (P < .05) and increased secondary bile acid concentrations (P < .0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed
an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal.

Adverse events were generally mild to moderate in severity.

Conclusions. Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial. Clinical Trials Registration. NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw=2&rank=4.

To view publication in its entirety please click on the following link to be redirected:

https://academic.oup.com/cid/search-results?page=1&q=SER-109%2C%20an%20Investigational%20Microbiome%20Drug%20to%20Reduce%20Recurrence%20After%20Clostridioides%20difficile%20Infection%3A%20Lessons%20Learned%20From%20a%20Phase%202%20Trial&fl_SiteID=5269&SearchSourceType=1&allJournals=1