Tag Archives: DEINOVE Phase II study DNV3837

DEINOVE: DNV3837 Antibiotic Candidate: the Phase II Clinical Trial to Treat CDI Continues in the USA

DEINOVE is a French biotech company that uses its lead generation platform to develop innovative anti-infective drugs, is pursuing the Phase II clinical trial of its antibiotic candidate DNV3837, in a context where U.S. hospitals are still fighting the COVID-19 pandemic. The Company thanks the clinicians for their commitment to this trial, as they face an unprecedented health crisis.

DNV3837 targets the treatment of Clostridioides difficile gastrointestinal infections (CDI), a pathogen classified as urgent threat by the U.S. Centers for Disease Control and Prevention (CDC). A Phase II clinical trial, launched in early 2020 in the United States, is evaluating the efficacy of DNV3837 in patients, following promising Phase I data. To date, DEINOVE is the only French biotech with a small molecule in clinical development, fully owned by the company, in the field of antibiotics.

This trial continues in the United States despite the COVID-19 outbreak. Several of the investigation centers have maintained their clinical research activities and continue to screen and include patients. DEINOVE scientific team and the CRO Medpace are closely monitoring the situation.

« We are grateful to the clinicians for doing their utmost to ensure that the clinical trial runs smoothly. We are surrounded by a team that is aware of the therapeutic stakes and the potential of our solution in development, and we thank them for this. In the current health conditions in the United States, where hospitals are overcrowded, we could have feared a suspension of the trial, » says Dr. Yannick Plétan, Acting Chief Medical Officer responsible for the clinical trial. «Conversely, the COVID-19 outbreak – which mainly affects the elderly – and the heavy antibiotic treatments administered to combat possible bacterial co-infections, are factors conducive to the development of severe Clostridioides difficile infections targeted by DNV3837. We are concerned, however, about the irrational use of antibiotics, which would have long-term public health consequences. »

On June 1st of this year, the WHO warned of the increasing rates of antimicrobial resistance, boosted by the current health crisis. ” The COVID19 pandemic has led to an increased use of antibiotics, which ultimately will lead to higher bacterial resistance rates that will impact the burden of disease and deaths during the pandemic and beyond,”worried Dr Tedros Adhanom Ghebreyesus, WHO Director-General1. According to him, the threat of antimicrobial resistance is “one of the most urgent challenges of our time “. He also recalled that only small proportion of COVID-19 patients need antibiotics to treat subsequent bacterial infections.

ABOUT CLOSTRIDIOIDES DIFFICILE INFECTIONS (CDI)

40% of patients suffering a Clostridioides difficile infection (CDI) have severe forms, with mortality rates as high as 50%. Over the past 20 years, CDIs tended to increase significantly in incidence and severity, particularly due to the development of new hypervirulent strains and the high risk of recurrence. The US Center for Disease Control and Prevention (CDC) recently identified CDIs as one of the leading causes of healthcare-associated infections before Staphylococcus aureus (MRSA2) infections. In 2017, in the United States, there were an estimated 223,900 cases in hospitalized patients and 12,800 deaths3. This disease does not affect the United States only, recent studies4 show that the incidence of this type of infection is vastly underestimated in other parts of the world such as Europe and Asia.

To date, there are no therapeutic solutions for patients with severe gastrointestinal infections. Since the oral route is compromised, the available treatments, which are mostly oral treatments, struggle to reach the intestine because of the patient’s pathological condition (reduced gastrointestinal motility, intubation, intestinal perforation, etc.), and the few antibiotics that could be administered intravenously (IV), do not cross the gastrointestinal barrier and therefore do not reach the site of infection.

ABOUT THE DNV3837 ANTIBIOTIC CANDIDATE

DNV3837 – a prodrug5 of the DNV3681 molecule (also known as MCB3681) – is a narrow-spectrum, hybrid oxazolidinone-quinolone synthetic antibiotic targeting only Gram-positive bacteria. It is developed as a highly active 1st line treatment targeting Clostridioides difficile.

It has demonstrated significant efficacy and superiority to reference treatments (fidaxomicin in particular) against isolates of C. difficile, regardless of their virulence (including the hyper virulent BI/NAP1/027 strain).

DNV3837 is an intravenous antibiotic that, when converted to its active form DNV3681, crosses the gastrointestinal barrier and accumulates in the intestinal lumen, allowing it to precisely target the infection site. Several Phase I trials (on approx. a hundred healthy volunteers) have shown a high concentration of the antibiotic in stools, a strong marker of its presence in the intestine. It has also demonstrated its ability to eliminate Clostridioides bacteria without affecting the gut microbiota. It has also shown an acceptable tolerance profile.

FDA granted the DNV3837 drug with Qualified Infectious Disease Product (QIDP) designation and Fast Track status.

ABOUT THE PHASE II CLINICAL TRIAL TESTING DNV3837 IN CDI

The antibiotic candidate DNV3837 has been in a Phase II trial since the end of January 2020. The purpose of this trial is to evaluate its efficacy in CDI (through monitoring of symptoms, stool analysis, etc.), as well as to consolidate the safety and pharmacokinetic data.

This trial is taking place in the United States in two stages:

  • In the first phase, a cohort of 10 patients with moderate to severe CDI is treated with DNV3837. At the end of this phase, the DSMB6 has scheduled to review the interim results.
  • The second phase involves 30 patients with severe CDI. This is an open-label randomized trial testing DNV3837 (in 2/3 of patients) against an approved standard of care7 (1/3 of patients) for comparison purposes.

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DEINOVE Announced Enrollment of First Patient in Phase II Trial Testing DNV3837 in Clostridioides difficile infections

On January 27, 2020, DEINOVE announced the inclusion of the first patient in the Phase II trial testing DNV3837.

 

  • The Phase II clinical trial aims to evaluate the efficacy, safety, and pharmacokinetics of DNV3837 in patients with Clostridioides difficile gastrointestinal infection (CDI).
  • The trial will be conducted mainly in 15 centers in the United States, in two successive stages:
    • a cohort of 10 patients with moderate to severe CDI treated with DNV3837,
    • a randomized cohort study testing DNV3837 against the standard of care in 30 patients with severe CDI.
  • The final results of this trial are expected by the end of 2020.
  • DEINOVE is the only French player to conduct a clinical trial with an antibiotic.
  • On 17 January, the WHO warned about the extreme lack of new antibiotics and the threat posed by antibiotic resistance.

DEINOVE (Euronext Growth Paris: ALDEI), a French biotech company that uses a disruptive approach to develop innovative antibiotics and bio-based active ingredients for cosmetics, announced the inclusion of the first patient in the Phase II trial testing DNV3837.

DNV3837 targets the treatment of Clostridioides difficile infections (CDI), a disease classified as a priority by the WHO and one of the global leading causes of healthcare-related infections*.

DNV3837 is an intravenous antibiotic that, when converted to its active form DNV3681, crosses the gastrointestinal barrier and accumulates in the intestinal lumen, allowing it to precisely target the infection site. DNV3837 has demonstrated a promising efficacy profile and acceptable tolerance in Phase I trials (on healthy volunteers). It has also demonstrated its ability to eliminate Clostridioides bacteria without affecting the gut microbiota. It has been granted Fast Track status and QIDP designation**.

The Phase II trial aims to evaluate the efficacy of DNV3837 in pathological conditions (through monitoring of symptoms, stool analysis, etc.), as well as to consolidate the safety and pharmacokinetic data of the antibiotic candidate.

This trial is concentrated in the United States. It will take place in two stages:

  • In the first phase, involving 5 centers, a cohort of 10 patients with moderate to severe CDI will be treated with DNV3837. At the end of this phase, the DSMB*** will review the interim results.
  • The second phase will involve 30 patients with severe CDI and will be carried out in 15 investigation centers. This will be an open-label randomized trial testing DNV3837 (in 2/3 of patients) against an approved standard of care**** (1/3 of patients) for comparison purposes.

The results of this clinical trial should be available by the end of 2020.

 “The start of this Phase II clinical trial is a significant step forward for DEINOVE and a great hope for patients. We are very proud to provide a potential solution to this unmet medical need and, to this end, work with the best American specialists in this area. The investigation centers are very committed to conducting this trial which, in the event of positive results, will be an important milestone towards the registration of DNV3837,” said Dr. Georges Gaudriault, Scientific Director of DEINOVE.

This announcement echoes warnings issued by the WHO about the lack of antibiotics renewal.

Dr. Tedros Adhanom Ghebreyesus, Director-General of WHO, declared last January 17 « Never has the threat of antimicrobial resistance been more immediate and the need for solutions more urgent ».

https://www.who.int/news-room/detail/17-01-2020-lack-of-new-antibiotics-threatens-global-efforts-to-contain-drug-resistant-infections

 

* Source: CDC (US Centers for Disease Control and Prevention)

** ‘Fast Track’ status facilitates the development of the molecule through a faster and more flexible regulatory review of the application. The QIDP designation gives the drug exclusive access to the market for an additional five-year period. These designations are granted by the FDA to drugs under development that meet critical and unmet therapeutic needs.

*** DSMB – Data Safety Monitoring Board: a group of independent experts tasked to review the data generated during the trial and make recommendations on patient safety as well as trial relevance and validity.

**** Standard treatments approved in the United States for the treatment of CDIs include vancomycin, fidaxomicin and metronidazole (all three antibiotics). The choice will be at the discretion of the clinicians. 

Deinove Phase II DNV3837 for C.difficile Infection Clinical Trial To Begin Mid 2019

Deinove is preparing initiation of Phase II for DNV3837 in Clostridium difficile infections, with a key partner

  • The test design has been improved for a better assessment of DNV3837 effectiveness in treating Clostridium difficile infections,
  • This will be a multicenter trial, taking place mostly in the United States, where the prevalence of the disease is high,
  • DEINOVE has chosen Medpace as its Clinical Research Organization (CRO)1 to prepare and oversee the trial, notably because of their experience with the target disease,
  • The trial is scheduled to begin mid-2019,
  • This clinical program will be the focal point of DEINOVE’s antibiotic strategy in the coming months, as the Company has decided not to exercise its option on the NBTI program.

DEINOVE (Euronext Growth Paris: ALDEI), a French biotech company that uses a disruptive approach to develop innovative antibiotics and bio-based active ingredients for cosmetics and nutrition, is preparing the Phase II study that will test DNV3837, its most advanced antibiotic candidate, for use against Clostridium difficile infections (CDI). DEINOVE has chosen Medpace (NASDAQ: MEPD) to act as its CRO and to oversee the clinical trial scheduled to begin in 2019.

DNV3837 is a first-in-class antibiotic candidate targeting the treatment of Clostridium difficile infections (CDIs), a disease classified as a priority by the WHO and one of the leading causes of healthcare-associated infections2. DNV3837 has demonstrated a promising efficacy profile and acceptable tolerance in Phase I trials. The FDA3 has already approved the start of a Phase II study and has granted the DNV3837 program the Qualified Infectious Disease Product (QIDP) designation and Fast Track status4 for accelerated product development.

DEINOVE acquired the DNV3837 program in the 1st half of 2018. Since then, their clinical development team has worked with a group of healthcare experts in CDI to prepare for the start of a Phase II clinical trial whose purpose is to demonstrate the efficacy of DNV3837 in patients suffering from CDI. Several aspects of the trial design, which had been presented to the FDA prior to the acquisition, have been improved:

  • the target patient population was expanded and now covers moderate to severe CDIs for greater progressiveness in treatment assessment;
  • it will be a multicenter trial with a major part taking place in the United States, where there is greater prevalence and the regulatory authorities are looking for new treatment options.

The design of the trial has now been finalized for submission of the updated version to the FDA. The selection process of clinical investigation centers is underway. The trial is scheduled to begin mid-year.

DEINOVE has chosen Medpace to oversee the trial. Medpace is an internationally-recognized full-service CRO that notably has a great deal of experience in infectious diseases, especially gastrointestinal infections like CDIs.

Its mission includes support for the clinical trial’s design and set-up (protocol review, contacting the clinical investigation centers, etc.), gathering and analyzing data, and interacting with the FDA.

Georges Gaudriault, Scientific Director at DEINOVE, said: “Preparations for the Phase II clinical trial for DNV3837 are moving forward as planned and we are delighted to have executed such an agreement with Medpace for this trial’s oversight. Their experience in both the pathology and American regulatory procedures will help us to secure and maximize this trial’s progress.”

The DNV3837 program is followed by the AGIR program (backed by Bpifrance), whose aim is to add to the portfolio of new molecules from DEINOVE’s biodiversity. The option on the NBTI5 program will indeed not be exercised, as the data gathered during the assessment phase were not considered to be in line with DEINOVE’s expectations for pursuing the program.

Emmanuel Petiot, CEO of DEINOVE, added: “The antibiotics field is a priority for DEINOVE and the DNV3837 program is our spearhead. Furthermore, we have decided not to exercise our option on the NBTI program with REDX Pharma, insofar as our teams’ assessment showed obstacles to its development without further optimization. We want to respond quickly and effectively to the health emergency and the lack of innovative antibiotics, and we are focusing our efforts on those programs with the highest possible probability of success.”

 

DNV3837 – a prodrug of the DNV3681 molecule (also known as MCB3681) – is a narrow-spectrum, hybrid oxazolidinone-quinolone synthetic antibiotic, targeting only Gram-positive bacteria. It is developed as a highly active 1st line treatment targeting Clostridium difficile.

It has demonstrated significant efficacy and superiority to reference treatments (fidaxomicin in particular) against isolates of C. diff., regardless of their virulence (including the hyper virulent strain NAP1).

DNV3837 is administered intravenously and is able to cross the gastrointestinal barrier, allowing it to precisely target the infection site. Several Phase I trials (on approx. one hundred healthy volunteers) have shown a high concentration of the antibiotic in stools, a strong marker of its presence in the intestine. It has also demonstrated its ability to eliminate C. diff. bacteria without altering the gut microbiota in the long term, a definite advantage for patient prognosis. It has also shown an acceptable tolerance profile.

FDA granted the DNV3837 program with Qualified Infectious Disease Product (QIDP) designation and Fast Track status.

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https://globenewswire.com/news-release/2019/01/31/1708049/0/en/Deinove-is-preparing-initiation-of-Phase-II-for-DNV3837-in-Clostridium-difficile-infections-with-a-key-partner.html