MD Magazine

An original version of this article was published on sister publication 

Enrollment for a phase 3 trial involving an investigative Rebiotix therapy for 

The clinical study of RBX2660 will be the first phase 3 trial in the history of the microbiome industry. The randomized, double-blinded study will include 300 patients with the gastrointestinal disease.

 microbiota-based therapy. RBX2660 has previously been granted Fast Track, Orphan, and Breakthrough Therapy Status designations from the FDA.

Fast Track designation allows the expedited review of an investigational drug which fulfills an unmet need. Orphan designation applies to a drug which meets a medical need but may not be profitable to produce without development incentives. Breakthrough Therapy Status expedites the review of a drug that preliminary evidence indicates may provide substantially better outcomes than existing therapies.

There are limited options for the treatment of 

available, and roughly 1 in 5 patients face a recurrence of 

infection, the likelihood of further recurrence increases.

 The company intends to use results from the trial to apply for FDA licensure.

Previous results from the phase 2 clinical trial of RBX2260 found the treatment safe and efficacious for preventing 

Ken Blount, PhD, chief scientific officer at Rebiotix, a Ferring Company, discussed the 

At 8 weeks, RBX2660 efficacy in preventing CDI recurrence (78.9%&#894;112/142) was higher than the CDI-free rate in the historical control group (30.7%, 23/75&#894; 

The safety profile of RBX2660 was also consistent with previous reports.

 hospital length of stay between 3 and 21 days, according to recent research. Recurrence places a substantial burden on patients and the health care system.

If the phase 3 trial shows further promising results, the trial would represent a major step forward for the growing field of microbiome-based interventions.

Articles

RBX2660 from Rebiotix will be assessed in a randomized study involving 300 patients.

Historic Phase 3 Microbiota Trial for C Diff Treatment Completes Enrollment

 has reached approximately 13 million people in the US.

According to the newest update to the US Centers for Disease Control and Prevention (CDC) 

 on data ending January 11, 2020, flu activity is high for the current season, yet disease severity is moderate.

At this point in the season, CDC estimates indicate that there have been 13 million influenza illnesses, 120,000 hospitalizations, and 6600 flu-related deaths.

The CDC notes that the number of respiratory specimens that tested positive for the flu at clinical laboratories decreased over the past week from 23.6% to 22.9%. Visits to clinicians for influenza-like illness also decreased from 5.7% last week to 4.7% this week; however, activity for all US regions remain above baseline. In fact, 34 jurisdictions are experiencing high influenza-like illness activity.

The percentage of deaths attributed to pneumonia and influenza also increased from 6.0% to 6.9%, but remains below the epidemic threshold

According to the report, the overall rate of influenza-associated hospitalization increased to 1.9 per 100,000. The highest rate of hospitalization has been observed among adults aged ≥65 (47.6 per 100,000 population), followed by children aged 0-4 years (34.4 per 100,000 population) and adults aged 50-64 years (23.2 per 100,000 population).

Although influenza B/Victoria viruses have been the 

 this season, new data reveal that during recent weeks equal numbers of B/Victoria and A(H1N1)pdm09 viruses have been reported.

This past week 7 new influenza-associated pediatric deaths were reported, bringing the seasonal total to 39. According to the FluView report, 28 deaths were linked to B viruses—5 of which had their lineage determined and were B/Victoria viruses&mdash;and the other 11 deaths were associated with A viruses, 6 of which were A(H1N1)pdm09 virus-associated.

“Unfortunately, [B viruses] seems to be taking a higher toll on very young children, more so than in previous years,” Aaron E. Glatt, MD, a spokesperson for the Infectious Diseases Society of America told 

“It doesn't necessarily mean that that's something that will continue or it's something that is intrinsically more dangerous to children. It's possible that they haven't been exposed to as much influenza B in their short lives. Even if they're relatively young, they may have seen some influenza A beforehand, and therefore, it's something that their body has somewhat been prepared for.”

Nationally, influenza B/Victoria viruses are the most commonly reported influenza viruses among children age 0-4 years (47% of reported viruses) and 5-24 years (57% of reported viruses). On the other hand, A(H1N1)pdm09 viruses are the most commonly reported viruses among the 25-64 years age group (46% of reported viruses) and 65 years and older (53% of reported viruses).

“From a clinician point of view, stress vaccination, even now,” Glatt, chairman of the Department of Medicine at Mount Sinai South Nassau in Oceanside, New York, and professor of medicine at Icahn School of Medicine at Mount Sinai, told 

“It’s obviously better to be vaccinated and have whatever benefit the vaccine gives you...and the vaccine will definitely have some benefits.”

The CDC notes that flu vaccine effectiveness estimates are not available yet this season, but vaccination is always the best way to reduce the risk of influenza and any associated complications.

“I personally would add that there is data to support the quadrivalent vaccine,” Glatt noted. “It has 2 strains of B, whereas the trivalent vaccine only has 1 strain. The official position says it doesn’t make a difference, but I would probably recommend the quadrivalent vaccine if they’re both available.”

New data for the 2019-2020 season shows the virus is at a high activity, but disease severity is moderate.

Flu Cases Reach 13 Million in the US, CDC Reports

The US Food and Drug Administration (FDA) has approved cefiderocol (Fetroja) for the treatment of complicated urinary tract infections (cUTI), including kidney infections caused by susceptible gram-negative microorganisms in particular adults.

Cefiderocol, from Shionogi Inc, is a siderophore cephalosporin. It is active against all classes of β-lactamases, which enables it to overcome the primary mechanisms of gram-negative bacterial resistance to β-lactam antibiotics. This indication is designated for patients with limited or no alternative treatment options.

The safety and effectiveness of cefiderocol was demonstrated in a study of 448 patients with cUTIs. In the study, 72.6% of patients who received cefiderocol had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared to 54.6% of patients who received an alternative antibiotic. The clinical response rates were similar between the treatment groups.

Labeling for cefiderocol includes a warning regarding the higher all-cause mortality rate observed in cefiderocol-treated patients compared to those treated with other antibiotics in the CREDIBLE-CR study in critically ill patients with multidrug-resistant gram-negative bacterial infections.

Last month, an FDA advisory committee voted 14-2 to back the efficacy of cefiderocol for cUTI. However, concern was expressed over increased mortality observed in the CREDIBLE-CR study, but complicating factors related to different condition states were suggested as the higher mortality rates were only observed in the hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) subgroup, as well as the bloodstream infection/sepsis subgroup, rather than the cUTI group.

According to the FDA, the cause of the increase in mortality has not been established. Some of the deaths were a result of worsening or complications of infection, or underlying co-morbidities. The agency also notes that safety and efficacy of cefiderocol has not been established for the treatment of HABP/VABP, bloodstream infections, or sepsis.

In clinical studies, the most common adverse reactions related to cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion site reactions, candidiasis, cough, headache and hypokalemia (low potassium). Cefiderocol should not be used in individuals with a known history of severe hypersensitivity to beta-lactam antibacterial drugs.

"The FDA approval of cefiderocol for complicated UTIs is in keeping with the recommendations made by the advisory committee who recognize the continued unmet medical need for new therapeutic options against multidrug resistant gram-negative bacteria, but cannot explain the higher mortality rates in the CREDIBLE-CR study," Ryan K. Shields, PharmD, MS, Contagion®’s Multidrug-Resistant Infections Section Editor, said on the approval. "The warning of higher all-cause mortality in the label will ideally serve as a reminder to clinicians that additional data are needed to evaluate the efficacy of this agent against MDR pathogens.

An original version of this article was published on MD Magazine® sister publication ContagionLive.

In the pivotal assessment, three-quarters of patients who received cefiderocol had resolution of symptoms and eradication of the bacteria 1 week after completing treatment, versus 54.6% of patients who received an alternative antibiotic.

FDA Approves Cefiderocol for cUTI

Adults with community-acquired bacterial pneumonia(CABP) now have a new therapy option with the decision of US Food and Drug Administration to award approval of delafloxacin(Baxdela) for treatment of CABP to Melinta Therapeutics.

The approval of delafloxacin, which was announced on October 24, comes after the supplemental New Drug Application received priority review based on previous Qualified Infectious Disease Product designation.

The approval is based on the results of a phase 3 randomized, double-blind study comparing the efficacy and safety of delafloxacin to moxifloxacin. The study results showed that IV-to-oral delafloxacin met the primary end point of statistical non-inferiority for early clinical response (ECR) at 96 hours (± 24 hours) after initiation in the intent-to-treat population with 88.9% ECR in patients who received delafloxacin compared to moxifloxacin (89.0%).

Additionally, delafloxacin was generally safe and well-tolerated. The sNDA follows FDA priority review based on the previous Qualified Infectious Disease Product designation. 

“We are pleased to announce the approval of Baxdela for the treatment of CABP in adults,” Jennifer Sanfilippo, interim chief executive officer of Melinta, said in a 

. “As previously disclosed, we are closely managing our liquidity position and continue to evaluate our potential strategic and other alternatives. As such, while we believe that Baxdela will play a significant role in the treatment of this potentially life-threatening illness, we are delaying the commercial launch of CABP until we have greater insight into our ability to secure additional sources of liquidity.”

The approval marks the second for delaflocaxin in recent years. The FDA had previously 

 delaflocaxin for the treatment of acute bacterial skin and skin structure infections in adults in June 2017. 

, George Sakoulas, MD, UC San Diego School of Medicine, discussed the dual indications of ABSSSI and CABP for some of the newer agents available.

"Some of our newer agents, omadacycline and delafloxacin, have obtained almost simultaneous approvals or simultaneous approvals for both ABSSSI and CABP. That speaks to 2 things…1) the illnesses are largely driven by gram-positive agents. So in skin infections, you have 

, either group A or group B or other beta-hemolytic 

. In community-acquired bacterial pneumonia, again, it’s a 

," he said. "Gram-negatives take on a more important role in both of those illnesses as the patient becomes more comorbid, more immunocompromised, and so they have relatively similar spectra to cover: 

"Skin, pneumonia, and UTI are the 3 most common infections that we see in hospitals," he continued. "And so getting drugs through the approval process through registration trials, it's easier to go for infections that are very easy to enroll in, ie, common ones like pneumonia and skin, in order to get a drug onto the marketplace rather than starting with an illness that might actually have a larger medical need for newer antibiotics but would be harder to enroll patients in, like bacteremias or osteomyelitis and so on. And so hence the very similar crossover and simultaneous approval for drugs with community-acquired bacterial pneumonia and ABSSSI."

This article was originally published in ContagionLive. 

The supplemental new drug application was approved based on results of a phase 3 trial in which IV-to-oral delafloxacin met the primary end point of statistical non-inferiority to moxifloxacin.