John Parkinson

This article was originally published in ContagionLive.

RBX2660, an investigational microbiota-based live biotherapeutic, is showing promise in 5 prospective trials for the reduction of recurrent 

Historically speaking, rCDI occurs in 20-30% of patients, and the rates can increase with each ensuing episode. This reoccurrence has been difficult for patients who suffer from it causing it to have lingering effects and creating quality-of-life issues. From the clinical perspective, providers who are seeing these patients are looking for additional therapeutics and modalities to treat it.

From the 5 prospective trials presented by Ferring Pharmaceuticals and Rebiotix, a Ferring Company, which included 723 actively-treated participants, RBX2660 reduced the recurrence of CDI, with up to 78.9% remaining recurrence-free for eight weeks post treatment.

Among participants who did not respond to initial treatment, an optional additional treatment course was administered, resulting in overall rates of treatment success of up to 84.4%. Most primary responders remained CDI-free for six months and up to two years, with a sustained clinical response success rate of up to 92.1% in the phase 3 program.

“These data provide the totality of evidence culminating in over a decade’s worth of work that demonstrates a consistent efficacy profile for RBX2660, and importantly, a consistent safety profile across five prospective trials,” Lindy Bancke, PharmD, head of Clinical Development at Rebiotix, said. “They reinforce the enormous potential of microbiome-based therapeutics to transform the care of people suffering from rCDI.”

Banke’s presented the research, which was titled, Efficacy of Investigational Microbiota-Based Live Biotherapeutic RBX2660 in Individuals with Recurrent 

 Infection: Data from Five Prospective Clinical Studies, at 

RBX2660 is a potential first-in-class microbiota-based live biotherapeutic being studied to deliver a broad consortium of diverse microbes to the gut to reduce rCDI. RBX2660 has been granted Fast Track, Orphan, and Breakthrough Therapy designations from the Food and Drug Administration.

“Among 5 trials with consistent investigational product and clinical endpoints, RBX2660 consistently reduced rCDI recurrence, with a majority of treatment responders remaining CDI-free for at least 6 and up to 24 months,” Bancke reported.

Articles

Data from 5 trials presented at ID Week 2021 are promising for the investigational biotherapeutic. 

RBX2660 Reduces Recurrent C Difficile Infections

Following lengthy testimony, the Vaccines and Related Biological Products Advisory Committee has voted against the 

 of the Pfizer-BioNTech COVID-19 vaccine booster dose by a count of 16-2.

The committee was asked to make a decision looking at the clinical trial C4591001, which compromised 329 participants, and determining if the safety and effectiveness of the data would support approval.

The booster dose represents a single shot of the 0.3 mL approximately 6 months after the second dose in individuals 16 years and older.

vote against recommending the approval of a booster dose

 for people 16 years and older, the VRBPAC decided to create a new question to vote on an Emergency Use Authorization (EUA) for a booster dose for people 65 years and older and those deemed high risk of COVID-19.

Based on the totality of scientific evidence available including the safety and effectiveness data from clinical trial C4591001 do the known and potential benefits outweigh the known and potential risks of a Pfizer-BioNTech COVID-19 Vaccine booster administered at least 6 months after completion of the primary series for use in:

Individuals at high risk of severe COVID-19

Committee members voiced their concerns about the lack of data to feel comfortable with having such a large amount of the American population eligible for the booster dose.

After the second vote, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Research and Evaluation, asked the committee for their opinion on health care workers and the booster dose.

They decided to pose a poll question to the committee about this group. The specific question was: should healthcare workers or others at high risk for occupational exposure be included in this EUA?

The committee voted 18-0 in favor of including healthcare workers.

The earlier meeting mainly centered on the effectiveness of the vaccine after several months and whether or not the booster is necessary to combat the Delta variant.

Sarah Oliver, MD, MSPH, Centers for Disease Control and Prevention Division of Viral Disease, National Center for Immunization and Respiratory Diseases, discussed vaccine rates, hospitalizations, and vaccine effectiveness.

To date, 380 million total vaccine doses administered, and the breakout in terms of the percentage of the population fully vaccinated for ages is the following:

From January-July 2021, COVID-19 hospitalization rates were 23 times higher in the unvaccinated in the 18-49 age group; 22 times higher in the unvaccinated in the 50-64 age group; and 13 times higher in the unvaccinated in those aged 65 years and older.

The vaccines’ effectiveness dropped considerable from the plus 90% range prior to the emergence of the Delta variant to dropping several percentage points after that strain became the predominant variant.

During the meeting, 2 Israeli investigators presented data regarding how that country dealt with an increase of COVID-19 and their booster strategy in order to try to stop it.

Sharon Alroy Preis, MD, MPH, MBA, director of Public Health Services, Ministry of Health, Israel during her presentation said Israel was vaccinated earlier than most other countries and up to 3 months before.

In the summer they saw a 10 fold increase in 1 month.

Their booster data they reported showed the following:

Ron Milo, PhD, Professor, Weizmann Institute, Israel, said there was “significant protection” with booster doses.

He explained that if VE after waning is 50 for infection and increases 10-fold it become 95%. If VE after waning is 80 for infection and increases 10-fold it becomes greater than 97%.

When asked about follow-up booster doses, Preis said it was too early to determine if people will need to be vaccinated every 6 months.

William C. Gruber, MD, senior vice president, Vaccine Clinical Research and Development Pfizer, presented for the company and said that immunity waned 6-8 months after the second dose when Delta variant is the predominant strain. In addition, a retrospective study showed that vaccine effectiveness (VE) decreased primarily due to waning vaccine induced immunity rather than due to Delta escaping vaccine protection.

Joohee Lee, MD, from the FDA, said the breakthrough infections happened more frequently to those who were vaccinated earlier than later. During her presentation Lee noted that immunogenicity data to support the effectiveness of the booster dose against the Delta variant are limited to exploratory analysis in a small number of participants using non-validated assays.

In the afternoon session during the public hearing people making presentations were mostly skeptical against the idea of a booster. More than a few were complaining over the size of the number of participants (329), the very small amount people who were 65 and older (12 participants), and the limitations on the Pfizer and Israel data.

After the public comment, there was a question and answer period and a discussion amongst the committee members. Paul Offit, MD, commented that he might be reluctant to vote yes for everyone 16 years or older, but would be open to voting for those 65 years and older.

As the committee was deliberating over the data and had their questions answered, some members seemed more inclined to want more data and that the current evidence did not confirm the need for a booster dose.

This discussion led to the vote and the aforementioned result.

The VRBPAC voted 16-2 against the booster dose because of unclear evidence regarding the need.

FDA Panel Advises Against Pfizer-BioNTech COVID-19 Booster Dose

 vaccine to gain Emergency Use Authorization (EUA) could be the first to garner full US Food and Drug Administration (FDA) approval, potentially as soon as Labor Day.

In the coming weeks the agency is expected to look at the full approval for the Pfizer-BioNTech vaccine, which received an EUA in December 2020.

“The FDA’s unofficial deadline is Labor Day or sooner, according to multiple people familiar with the plan. The agency said in a statement that its leaders recognized that approval might inspire more public confidence and had “taken an all-hands-on-deck approach” to the work,” according to a report in the 

The report also stated that if full approval is authorized, there is an expectation that medical centers, the Defense department and San Francisco will mandate vaccinations for their employees.

The emergence of the Delta variant, which has become the predominant strain in the US, has pushed public health officials and the federal government to act. There has been a renewed push for both vaccination as well as a recommendation to wear masks again—even for the fully vaccinated.

US Centers for Disease Control and Prevention (CDC) Director Rochelle Walensky, MD, noted the change due to new data in an address last week.

"In recent days I have seen new scientific data from recent outbreak investigations showing that that Delta variant behaves uniquely differently from past strains of the virus that cause COVID-19," Walensky, said. "This new science is worrisome and unfortunately warrants an update to our recommendations."

 specifically asked vaccinated people to wear masks again when indoors in public settings in parts of the US with “substantial” to “high” transmission. The CDC created a 

 on its site to help the public determine the level of transmission in the county they live in.

The CDC also reversed its recommendations on mask wearing in schools, stating that all teachers, administrators, staff, students, and visitors should wear a mask indoors regardless of vaccination status.

Would mark the first COVID-19 vaccine to gain full FDA approval.

FDA Could Approve Pfizer-BioNTech COVID-19 Vaccine by September

New guidance from the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) includes 3 new evidence-based guidelines for the treatment of 

The guidelines, developed by a multidisciplinary panel with representatives from IDSA and SHEA and announced on June 24, include 3 recommendations on suggested treatments for patients with initial and recurring CDI episodes, based on new data for fidaxomicin and for bezlotoxumab, a monoclonal antibody targeting toxin B produced by 

The guidelines call for patients with an initial CDI to be treated with fidaxomicin as opposed to vancomycin.

According to the panel, the recommendations are the result of systematic review of available evidence and an assessment of the benefits and harms of alternative care options.

The panel adhered to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence and strength of recommendations.

The guidelines are intended to aid clinicians in determining which treatments are best for individual patient scenarios.

Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults

IDSA and SHEA released 3 new evidence-based recommendations for treating CDI.