Tag Archives: Bezlotoxumab

Researchers Report Bezlotoxumab Treatment Reduced C. diff. Recurrence in Cancer Patients

Abstract

Background

The incidence of Clostridioides difficile infection (CDI) is reportedly higher and the cure rate lower in individuals with cancer versus those without cancer. An exploratory post-hoc analysis of the MODIFY I/II trials (NCT01241552/NCT01513239) investigated how bezlotoxumab affected the rate of CDI-related outcomes in participants with cancer.

Methods

Participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI antibacterial treatment. A post-hoc analysis of CDI-related outcomes was conducted in subgroups of MODIFY I/II participants with and without cancer.

Results

Of 1,554 participants in the modified intent-to-treat (mITT) population, 382 (24.6%) were diagnosed with cancer (bezlotoxumab 190, placebo 192). Of participants without cancer, 591 and 581 received bezlotoxumab and placebo, respectively. In the placebo group, initial clinical cure (ICC) was achieved by fewer cancer participants versus participants without cancer (71.9% versus 83.1%; absolute difference [95% CI]: -11.3% [-18.6, -4.5]), however, CDI recurrence (rCDI) rates were similar in cancer (30.4%) and non-cancer (34.0%) participants. In participants with cancer, bezlotoxumab treatment had no effect on ICC rate compared with placebo (76.8% versus 71.9%), but resulted in a statistically significant reduction in rCDI versus placebo (17.8% versus 30.4%; absolute difference [95% CI]: 12.6% [-22.5, -2.7]).

Conclusions

In this post-hoc analysis of participants with cancer enrolled in MODIFY I/II, the rate of rCDI in bezlotoxumab-treated participants was lower than in placebo-treated participants. Additional studies are needed to confirm these results.

Open Forum Infectious Diseases, ofaa038, https://doi.org/10.1093/ofid/ofaa038
Published:
31 January 2020

 

To access the article in its entirety please click on the following link:

https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa038/5718256

Study Assessed Bezlotoxumab Cost Effectiveness Added To Standard of Care to Prevent rCDI In High-risk Patients From the Spanish National Health System

Abstract

Introduction

Clostridium difficile infection (CDI) is the major cause of infectious nosocomial diarrhoea and is associated with considerable morbidity, mortality and economic impact. Bezlotoxumab administered in combination with standard of care (SoC) antibiotic therapy prevents recurrent CDI.

This study assessed the cost-effectiveness of bezlotoxumab added to SoC, compared to SoC alone, to prevent the recurrence of CDI in high-risk patients from the Spanish National Health System perspective.

Methods

A Markov model was used to simulate the natural history of CDI over a lifetime horizon in five populations of patients at high risk of CDI recurrence according to MODIFY trials: (1) ≥ 65 years old; (2) severe CDI; (3) immunocompromised; (4) ≥ 1 CDI episode in the previous 6 months; and (5) ≥ 65 years old and with ≥ 1 CDI episode in the previous 6 months. The incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed.

Results

In all patient populations (from 1 to 5), bezlotoxumab added to SoC reduced CDI recurrence compared to SoC alone by 26.4, 19.5, 21.2, 26.6 and 39.7%, respectively. The resulting ICERs for the respective subgroups were €12,724, €17,495, €9545, €7386, and €4378. The model parameters with highest impact on the ICER were recurrence rate (first), mortality, and utility values. The probability that bezlotoxumab was cost-effective at a willingness-to-pay threshold of €21,000/QALY was 85.5%, 54.1%, 86.0%, 94.5%, 99.6%, respectively.

Conclusion

The results suggest that bezlotoxumab added to SoC compared to SoC alone is a cost-effective treatment to prevent the recurrence of CDI in high-risk patients. The influence of changes in model parameters on DSA results was higher in patients  ≥ 65 years old, with severe CDI and immunocompromised. Additionally, PSA estimated that the probability of cost-effectiveness exceeded 85% in most subgroups.

To review article in its entirety, please click on the following link:

https://link.springer.com/article/10.1007/s12325-018-0813-y

Zinplava has been launched by MSD in the UK

MSD has launched Zinplava in the UK, offering patients a novel therapeutic option for the prevention of Clostridium difficile recurrence.

Zinplava (bezlotoxumab) is not an antibacterial and is not indicated to actually treat the infection, but is a monoclonal antibody designed to neutralise C. difficile toxin B, which can damage the gut wall and cause inflammation, leading to diarrhoea.

It is the first and only EC licensed non-antibiotic option indicated to prevent recurrence of Clostridium difficile infection (CDI) in high-risk adults.

Around one-in-four patients experience a recurrence after the initial episode, and more than 40 percent of these have further recurrence, highlighting the need for new options able to break the infection cycle.

Pivotal Phase III clinical studies showed the rate of infection recurrence through week 12 to be significantly lower in patients given Zinplava (17.4 percent and 15.7 percent) or Zinplava and actoxumab (15.9 percent and 14.9 percent) than those taking a placebo (27.6 percent) and (25.7 percent), respectively.

“Notably, bezlotoxumab reduces the risk of the recurrence of CDI for at least 3 months, compared with standard of care antibiotic therapy. This is welcome addition to our limited options to reduce the considerable morbidity and mortality associated with CDI,” commented Mark Wilcox, Professor of Medical Microbiology at the University of Leeds.

“Antimicrobial resistance is a key national issue and we hope with bezlotoxumab to not only help achieve a reduction in the number of recurrent episodes of CDI but also a reduction in the amount of antibiotic prescriptions that would otherwise be needed to treat these recurrent episodes,” added Dr Mike England, MSD’s Interim Medical Director.

Zinplava is administered as a single, one-off, one-hour intravenous infusion alongside standard-of-care antibiotic therapy for the treatment of CDI.

 

ZINPLAVA (bezlotoxumab) Is Now Available For Prescription To Reduce Recurrence Of Clostridium difficile Infection (CDI)

MERCKBW2015_medLogoBLK [Converted] (2)

ZINPLAVA (bezlotoxumab) is now available for prescription.

Ordering information is available on the brand website:

http://www.zinplava.com/

What is Zinplava™ ?

ZINPLAVA™ is indicated to reduce recurrence of Clostridium difficile infection (CDI) in patients 18 years of age or older who are receiving antibacterial drug treatment of CDI and are at a high risk for CDI recurrence.

ZINPLAVA is not indicated for the treatment of CDI.

ZINPLAVA is not an antibacterial drug.

ZINPLAVA should only be used in conjunction with antibacterial drug treatment of CDI.

Full prescribing information can be read at

http://www.merck.com/product/usa/pi_circulars/z/zinplava/zinplava_pi.pdf

The Merck Access Program can help answer physician’s questions about:
Insurance coverage for patients
Prior Authorizations and Appeals
Coding and Billing
Potential financial assistance options for eligible patients

Full program details can be found at:

https://www.merckaccessprogram-zinplava.com/hcp/

Also, Information about co-pay assistance for eligible, privately insured patients
Information about available independent assistance foundation support.

 

*PLEASE NOTE – The C Diff Foundation does not endorse any product, medication,  and/or clinical study in progress and available.     All website postings are strictly for informational purposes only.

 

Recurrent Clostridium difficile (C.diff.) Bezlotoxumab For the Prevention of Recurrent CDI

newsspeaker

Abstract Published: 2017 Jan 26

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

 

Recurrent Clostridium difficile Prevention

Wilcox MH1, Gerding DN1, Poxton IR1, Kelly C1, Nathan R1, Birch T1, Cornely OA1, Rahav G1, Bouza E1, Lee C1, Jenkin G1, Jensen W1, Kim YS1, Yoshida J1, Gabryelski L1, Pedley A1, Eves K1, Tipping R1, Guris D1, Kartsonis N1, Dorr MB1; MODIFY I and MODIFY II Investigators.
Author information
Abstract

Background Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy.

Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively.

Methods –  We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis.

The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population.

Results In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome.

The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively.

The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea.

Conclusions Among participants receiving antibiotic treatment for primary or recurrent
C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo.

The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).
Also Resource:

https://www.ncbi.nlm.nih.gov/pubmed/28121498

Bezlotoxumab – A New Agent for Clostridium difficile Infection. [N Engl J Med. 2017]