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MGB Biopharma Developing MGB-BP-3 a Treatment for CDI – Announces the Successful Completion of Its End-of-Phase 2 Meeting With the FDA

MGB Biopharmaa 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 AlbertaCalgary (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.

About MGB-BP-3

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 StrathclydeGlasgow, 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 more information, please visit www.mgb-biopharma.com

Research Provides New Data; C. difficile Changes In Testing and Management

 

 

 

 

 

 

Changes in Testing

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[14]: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[7]: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

Treatment Changes

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.

Microbiota Disruption

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[5]: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[7533]: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.

 

Source:  https://www.idse.net/Bacterial-Infections/Article/12-20/C-difficile-Old-Disease-New-Changes-In-Management/62162

C Diff Foundation Members Are Here For YOU Especially During the Pandemic

To Our Dear Patients, Families, and Healthcare Professionals,

To say these times have been trying is a giant understatement. We hope that you and your families are staying safe during this period of self quarantine, social distancing and limiting your daily exposures to help flatten the curve of COVID-19.

If anything is to come of this, we hope that it will be the value of hand washing, which will in turn help to prevent the spread of Healthcare-associated infections (HAI’s).

COVID-19 is in the forefront and this pandemic has majorly changed our lives. We are living through this together while healthcare professionals, across the globe, are dedicated  in developing the best possible practices for infection prevention, treatments and safety in public health.  For up-to-date COVID-19 information, please visit the CDC website:  www.cdc.gov

Be rest assured that the C Diff Foundation members continue to work diligently to educate and advocate for C. diff.  Infection prevention,  treatments, clinical trials, diagnostics, environmental safety and support to help those diagnosed with, being treated for, and recovering from a
C. diff. Infection worldwide.

Should you find yourself needing assistance with C. diff. infection information and support, please do not hesitate to contact us. We are here for you, your families, friends and healthcare professionals to see you through, and beyond a C. diff. infection.

A huge thank you goes out from all of us here at the C Diff Foundation to the brave men and women on the front lines of this pandemic. Without you and your bravery,  we would be in a major state of disarray. Thank you for being a guiding light for us all worldwide.

Check in on your neighbors, friends and families to make sure that they are okay. Keep your spirits high and know that we will get through this together.

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

C Diff Foundation Members Are Here For YOU Even During the Pandemic

To Our Dear Patients, Families, and Healthcare Professionals,

To say these times have been trying is a giant understatement. We hope that you and your families are staying safe during this period of self quarantine, social distancing and limiting your daily exposures to help flatten the curve of COVID-19.

If anything is to come of this, we hope that it will be the value of hand washing, which will in turn help to prevent the spread of Healthcare-associated infections (HAI’s).

COVID-19 is in the forefront and this pandemic has majorly changed our lives. We are living through this together while healthcare professionals, across the globe, are dedicated  in developing the best possible practices for infection prevention, treatments and safety in public health.  For up-to-date COVID-19 information, please visit the CDC website:  www.cdc.gov

Be rest assured that the C Diff Foundation members continue to work diligently to educate and advocate for C. diff.  Infection prevention,  treatments, clinical trials, diagnostics, environmental safety and support to help those diagnosed with, being treated for, and recovering from a
C. diff. Infection worldwide.

Should you find yourself needing assistance with C. diff. infection information and support, please do not hesitate to contact us. We are here for you, your families, friends and healthcare professionals to see you through, and beyond a C. diff. infection.

A huge thank you goes out from all of us here at the C Diff Foundation to the brave men and women on the front lines of this pandemic. Without you and your bravery,  we would be in a major state of disarray. Thank you for being a guiding light for us all worldwide.

Check in on your neighbors, friends and families to make sure that they are okay. Keep your spirits high and know that we will get through this together.

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

What Is SARS-CoV-2 and the Disease It Causes Named coronavirus disease 2019 or Better Known As COVID-19

 

 

 

What is Coronavirus?

The virus has been named “SARS-CoV-2” and the disease it causes has been named “COVID-19.”

Coronaviruses are a large family of viruses that may cause respiratory illnesses in humans ranging from common colds to more severe conditions such as Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS).

‘Novel coronavirus’ is a new, previously unidentified strain of coronavirus. The novel coronavirus involved in the current outbreak has been named SARS-CoV-2 by the World Health Organization (WHO). The disease it causes has been named “coronavirus disease 2019” (or “COVID-19”).

 

LISTEN AT YOUR LEISURE

Special Episode with Dr. Teena Chopra, MD, MPH

and Jennifer Wood, C. diff. Survivor – discussing the COVID-19 and C. difficile infection information

 

How does the virus spread?

COVID-19 can spread from person to person usually through close contact with an infected person or through respiratory droplets that are dispersed into the air when an infected person coughs or sneezes.  It may also be possible to get the virus by touching a surface or object contaminated with the virus and then touching your mouth, nose or eyes, but it is not thought to be the main way the virus spreads.

 

 

Where has COVID-19 spread to?

As of the March 6, 2020, there are over 95,000 confirmed cases of infection by the virus—and 3,381 of that number have resulted in death. While most cases of COVID-19 infection are in China, the virus has spread to 88 other countries.

What are the symptoms?

Similar to other respiratory illnesses, the symptoms of COVID-19 may include fever, cough, and shortness of breath.

People infected with COVID-19 may experience any range of these symptoms along with aches and pains, nasal congestion, runny nose, sore throat and diarrhea. Symptoms can start to show up anywhere from two to 14 days after exposure to the virus3. It may be possible for an infected person who is not yet showing any symptoms to spread the virus. Older persons, and those with pre-existing medical illnesses like heart disease and diabetes, however, seem to be more likely to experience severe respiratory symptoms and complications.

How to protect yourself from coronavirus

The best preventative action is to avoid being exposed to the virus. You can do this by taking a few cautionary steps—the same as you would if you were trying to avoid getting any respiratory illness.

  1. Wash your hands with soap and water frequently. If soap and water are not readily accessible, use alcohol-based sanitizers.
  2. Avoid contact with sick people.
  3. Avoid touching your eyes, nose, and mouth with your hands if they are unwashed.
  4. Cover your mouth and nose with a tissue or your bent elbow when you sneeze or cough. Make sure to dispose of the tissue immediately.
  5. If you are feeling unwell, stay home.
  6. If you have no respiratory symptoms such cough, a medical mask is not necessary.  Only use the mask if you have symptoms such as coughing or sneezing or suspect a COVID-19 infection. A mask is recommended for those caring for anyone with COVID-19.

What to do if you suspect you are infected?

The symptoms of COVID-19 are very similar to those of a cold or the flu, making it challenging to identify the specific cause of any respiratory symptoms. If you suspect you have been infected by COVID-19, you should seek medical care as soon as possible.

Until you can access medical care, you should follow these guidelines to reduce your likelihood of infecting others:

  • Restrict your outdoor activities and stay at home as much as you can. If it is feasible, stay in a separate room, and use a different bathroom from others in your household.
  • Clean and/or disinfect objects and surfaces that you touch regularly.
  • Track your symptoms as accurately as possible, so you can provide medical personnel with useful information.

Are there any treatments or vaccines?

There are currently no treatments, drugs, or vaccines available to treat or prevent COVID-19. People infected with the virus should receive medical treatment to relieve and alleviate the symptoms they are experiencing.

For Additional Information Please Visit the CDC Website:

https://www.cdc.gov/coronavirus/2019-ncov/about/index.html

 

Resource:  https://www.gethealthystayhealthy.com/articles/what-know-about-coronavirus-covid-19-explained