Bezlotoxumab
Prevention of Clostridium difficile infection (CDI) recurrence in patients aged 18 years or older with confirmed diagnosis of toxin B positive CDI, who are at high risk of CDI recurrence and receiving antibiotics for CDI.
Decisions on record
- Meeting Mar 2020 Not recommended Bezlotoxumab is indicated for the prevention of recurrence of Clostridium difficile infection (CDI) in adult patients 18 years or older at high risk for recurrence of CDI who are receiving antibiotic therapy for CDI
- Meeting Jul 2019 Not recommended The prevention of recurrence of Clostridium difficile infection (CDI) in adult patients 18 years or older at high risk for recurrence of CDI who are receiving antibiotic therapy for CDI.
- Meeting Jul 2018 Not recommended Indicated for the prevention of recurrence of Clostridium difficile infection (CDI) in adult patients 18 years or older at high risk of recurrence of CDI who are receiving antibiotic therapy for CDI. ZINPLAVA is not indicated for the treatment of CDI. ZINPLAVA is not an antibacterial drug. ZINPLAVA
- Meeting Nov 2017 Not recommended Prevention of Clostridium difficile infection (CDI) recurrence
Access path
- Nov 2017Not recommended
unclear definition of high-risk population, risk of use outside restricted population, likely repeat dosing despite…
- Jul 2018Not recommended
Comparator changed: placebo/standard of care antibiotics → standard of care (SoC)…
- Jul 2019Not recommended
modest clinical benefit for patients with ≥2 of 4 risk factors, poorly justified and inappropriate restriction criteria…
- Mar 2020Not recommended
modest clinical benefit, concerns about safety (particularly cardiac failure serious adverse events), uncertain and…
From the public summary
The PBAC did not recommend the listing of bezlotoxumab on the PBS for the prevention of Clostridium difficile infection (CDI) on the basis of uncertain clinical need, its modest effectiveness and concerns regarding safety, along with an uncertain incremental cost-effectiveness ratio (ICER).PSD · Mar 2020
The PBAC noted that the resubmission requested listing for a new high risk population, defined as ≥1 of 3 risk factors (age ≥65 years; history of CDI in past 6 months; immunocompromised due to haematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT)). The PBAC considered that restricting the population to age ≥65 years and history of CDI in past 6 months was consistent with the Committee’s July 2019 advice.PSD · Mar 2020
The structure of the modelled economic evaluation remained unchanged from previous submissions; however, the resubmission updated model inputs including the assumed CDI recurrence rate for SoC, population characteristics for the revised high risk population, and price per vial of bezlotoxumab.PSD · Mar 2020
In July 2018 and in reference to patients with ≥1 of 4 or 5 risk factors, the PBAC considered that the most informative analysis for decision making was to apply the following parameters (paragraph 7.6; bezlotoxumab, Public Summary Document, July 2018 PBAC meeting): 10-year time horizon; Hazard ratio (HR) for mortality due to CDI 1.12; 2.5% mortality without CDI recurrence; Hospitalisation costs as per AR-DRG (i.e.PSD · Mar 2020
The resubmission described bezlotoxumab with SoC as superior in terms of effectiveness compared with SoC and non-inferior in terms of safety compared to SoC, for patients with ≥ 1 of 2 risk factors (age ≥ 65 years; history of CDI in past 6 months); the resubmission did not make a clinical claim for immunocompromised patients due to history of HSCT or SOT.PSD · Mar 2020
In terms of comparative effectiveness, the data presented in the resubmission supported the claim of superior effectiveness for patients with ≥1 of 2 risk factors. The PBAC had previously considered that the MODIFY trials supported the claim of superior effectiveness for the previous populations but the overall benefit was modest and clinical significance was unclear (paragraph 7.5, bezlotoxumab, Public Summary Document, November 2017 PBAC meeting; …PSD · Mar 2020
6.2 The PBAC noted and welcomed the input from an individual (1) via the Consumer Comments facility on the PBS website, which described a range of benefits of treatment with bezlotoxumab, including the ability to return to normal life and avoidance of further CDI.PSD · Nov 2017
The resubmission proposed a special pricing arrangement with effective DPMQ for bezlotoxumab of $''''''''''' per vial (public hospitals) (versus a published price of $4,365).PSD · Mar 2020
Cost-effectiveness
ICER value is redacted in the PSD; published price and effective price contain redacted figures (''''''''''''''), making the ICER calculation incomplete in the public document.
Decision context
PopulationPatients aged 18 years or older with confirmed toxin B positive CDI, receiving oral antibiotics, at high risk of CDI recurrence defined as having one or more of: age ≥65 years, history of CDI in the past 6 months, or immunocompromised due to history of haematopoietic stem cell or solid organ transplant.
Risk sharingThe resubmission proposed a risk sharing arrangement with special pricing arrangements, but provided limited detail. The PBAC had previously advised that a risk sharing arrangement with a 100% rebate over financial caps would be needed to address uncertainty.
Why it was knocked back
- modest clinical benefit, concerns about safety (particularly cardiac failure serious adverse events), uncertain and unfavourable cost-effectiveness, uncertain financial estimates, high opportunity cost, lack of clinical trial data for immunocompromised population with HSCT or SOT
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2020 | Not recommended | Standard of care (SoC) antibacterial therapy including but not limited to vancomycin/metronidazole | — | RCT · Prevention of CDI recurrence |
| Jul 2019 | Not recommended | standard of care (SoC) antibacterial therapy including vancomycin/metronidazole | — | RCT · CDI recurrence |
| Jul 2018 | Not recommended | standard of care (SoC) antibiotic therapy including vancomycin and metronidazole | — | RCT · CDI recurrence |
| Nov 2017 | Not recommended | placebo/standard of care antibiotics | — | RCT · CDI recurrence |
Consumer voice
No consumer comments were received for this item.
The PBAC noted that no consumer comments were received for this item. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to toxin B positive CDI and defines high-risk criteria (age ≥65, prior CDI, immunocompromised), narrowing the TGA's broader 'high risk' definition.