Mundipharma Reports Additional Phase III ReSPECT Results Supporting REZZAYO for Invasive Fungal Disease Prevention After Stem Cell Transplantation
Mundipharma has announced additional findings from the global Phase III ReSPECT clinical trial evaluating REZZAYO® (rezafungin acetate) for the prevention of invasive fungal diseases (IFDs) in adults undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). The additional results were presented as a late-breaking oral presentation at IDWeek 2026, providing further details on the efficacy, safety, and clinical outcomes associated with once-weekly intravenous rezafungin compared with a standard antimicrobial prophylaxis regimen.
The findings expand on the topline ReSPECT results announced in April 2026, which showed that the study met its primary endpoint by demonstrating the non-inferiority of rezafungin to the standard antimicrobial regimen for fungal-free survival (FFS) at Day 90 following transplantation. The newly presented analyses included additional evaluations of the components contributing to FFS, pre-specified sensitivity analyses, fungal infection outcomes, and detailed safety results.
According to Mundipharma, the additional analyses were consistent with the previously announced topline findings. FFS at Day 90 was 60.7% among patients receiving rezafungin and 59.0% among those receiving the standard antimicrobial regimen. The estimated treatment difference was 1.6 percentage points, with a 95% confidence interval (CI) of -6.2 to 9.3 and a P value of 0.0002 for non-inferiority.
The results provide further clinical evidence supporting the investigation of rezafungin as a prophylactic option for patients undergoing allo-HSCT, a population at increased risk of serious fungal infections because of treatment-related immunosuppression. Data from the ReSPECT programme have been submitted to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for regulatory review.
In the United States, the FDA has granted Priority Review for the investigational prophylaxis use, with a Prescription Drug User Fee Act (PDUFA) target action date in the first quarter of 2027. However, rezafungin prophylaxis following allo-HSCT is not currently an approved indication.
ReSPECT Trial Demonstrates Non-Inferiority for Fungal-Free Survival
ReSPECT was a global, multicentre, randomised, double-blind Phase III study designed to compare once-weekly intravenous rezafungin with a standard antimicrobial prophylaxis regimen for preventing invasive fungal disease in adults undergoing allo-HSCT.
A total of 602 patients were randomised in the study, including 402 assigned to rezafungin and 200 assigned to the standard antimicrobial regimen. Patients were treated and evaluated through Week 13 following transplantation, with the primary endpoint assessing fungal-free survival at Day 90.
The primary endpoint was a composite measure incorporating three components: survival, the absence of proven or probable invasive fungal disease as assessed by an independent Data Review Committee, and no use of non-study systemic antifungal therapy for more than 10 cumulative days.
This composite endpoint was designed to evaluate outcomes beyond the occurrence of fungal infection alone. It also considered mortality and the need for additional systemic antifungal treatment outside the assigned study regimen.
At Day 90, fungal-free survival was 60.7% in the rezafungin group compared with 59.0% in the standard antimicrobial group. The estimated treatment difference of 1.6 percentage points met the study’s pre-specified non-inferiority criterion.
Non-inferiority trials are designed to determine whether a treatment’s performance is not unacceptably worse than that of an established comparator within a pre-defined statistical margin. In this study, the findings supported the conclusion that rezafungin was non-inferior to the standard antimicrobial regimen for the primary endpoint.
The primary analysis was further supported by six pre-specified sensitivity analyses. These examined different approaches to handling indeterminate outcomes, definitions of invasive fungal disease, randomisation stratification factors, and the use of non-study systemic antifungal therapy.
According to Mundipharma, the sensitivity analyses were consistent with the primary findings, providing additional support for the robustness of the results across the alternative analytical approaches.
Nevertheless, the study’s findings establish non-inferiority for the specified composite endpoint rather than superiority over standard prophylaxis. Further interpretation must also account for the individual components of the endpoint and the clinical characteristics of the transplant population.
Additional Analysis of Fungal-Free Survival Components
The additional ReSPECT results provide a more detailed assessment of the events contributing to failure of fungal-free survival.
Proven or probable invasive fungal disease contributed to FFS failure in 3.5% of patients receiving rezafungin, compared with 4.5% of patients receiving the standard antimicrobial regimen.
Death contributing to FFS failure occurred in 4.5% of patients in the rezafungin group and 5.5% in the comparator group.
The need for non-study systemic antifungal therapy for more than 10 cumulative days was also numerically lower among patients receiving rezafungin. This outcome occurred in 27.4% of the rezafungin group and 32.5% of the standard antimicrobial group.
These results provide further context for understanding the overall FFS findings. The observed percentages for proven or probable fungal disease and death were numerically lower in the rezafungin group, as was the percentage of patients requiring extended use of non-study systemic antifungal therapy.
However, the numerical differences in individual endpoint components should not automatically be interpreted as evidence of statistically significant differences for those outcomes. The reported primary conclusion relates to non-inferiority for the composite FFS endpoint, and separate statistical conclusions would require the relevant analyses.
The composite endpoint is particularly important in the transplant setting because patients may experience several competing clinical events during recovery. A patient may remain free of a documented fungal infection but still require additional antifungal treatment, while mortality can prevent subsequent assessment of infection-related outcomes.
By incorporating these elements, the ReSPECT study sought to provide a broader assessment of the clinical course of patients receiving antifungal prophylaxis after allo-HSCT.
Fungal Infections Reported by Species
The study also reported the incidence of invasive fungal diseases associated with individual fungal species.
Among patients receiving rezafungin, Candida infections occurred in 1.2% of patients, compared with 1.0% in the standard antimicrobial group. Aspergillus infections occurred in 2.0% of the rezafungin group and 3.0% of the comparator group.
Pneumocystis jirovecii infections were reported in 0.2% of patients receiving rezafungin, compared with 0% among those receiving the standard antimicrobial regimen.
These species-specific results offer additional information about the types of fungal infections observed during the trial. The findings indicate that the incidence of individual infections varied between treatment groups, with lower reported percentages for Aspergillus infections in the rezafungin group and similar percentages for Candida infections.
The results must be interpreted in the context of the overall study design, the relatively low percentages reported for individual fungal infections, and the fact that the trial’s primary endpoint was a composite measure of fungal-free survival.
The prevention of invasive fungal disease remains a critical component of care for allo-HSCT recipients. Invasive infections can cause substantial morbidity and mortality in immunocompromised patients, making the evaluation of preventive strategies an important area of clinical research.
Safety Findings Show No New Safety Signals
Mundipharma also reported detailed safety outcomes from ReSPECT. Treatment-emergent adverse events were reported in 99.7% of patients receiving rezafungin and 100% of patients receiving the standard antimicrobial regimen.
Serious adverse events occurred in 66.0% of patients in the rezafungin group and 67.5% in the standard antimicrobial group.
Treatment-emergent adverse events leading to study discontinuation occurred in 9.3% of patients receiving rezafungin, compared with 14.7% of those receiving standard antimicrobial prophylaxis.
Adverse events leading to dose reduction, treatment interruption, or withdrawal of study treatment occurred in 31.0% of the rezafungin group and 47.7% of the standard antimicrobial group.
According to Mundipharma, no new safety signals were identified among allo-HSCT recipients in the study.
The high overall incidence of treatment-emergent adverse events in both groups should be considered in the context of the underlying patient population. Adults undergoing allogeneic stem cell transplantation frequently experience substantial treatment-related complications and may require complex supportive care during the post-transplant period.
The reported findings suggest that adverse events were common in both study groups, while the percentages of patients experiencing adverse events that led to treatment discontinuation or dose modification were numerically lower in the rezafungin group.
These observations provide additional information about treatment tolerability but do not, on their own, establish a statistically significant safety advantage. Comprehensive interpretation requires consideration of the nature, severity, duration, and attribution of individual adverse events, alongside the study’s full safety analyses.
Addressing Unmet Needs in Antifungal Prophylaxis
Invasive fungal disease is a serious complication for patients undergoing allo-HSCT because transplantation and associated treatments can substantially weaken immune defenses.
Allogeneic haematopoietic stem cell transplantation involves the transfer of blood-forming stem cells from a donor to a recipient. It is used in the management of selected haematological malignancies and other serious disorders, but the treatment process can leave patients vulnerable to infections during periods of immune suppression.
Antifungal prophylaxis is an important part of supportive care for these patients. Preventive treatment aims to reduce the risk of fungal infections before they develop into potentially life-threatening complications.
Despite established prophylactic approaches, clinical challenges remain. These may include drug toxicities, drug–drug interactions, antifungal resistance, the need for therapeutic drug monitoring, and difficulties with daily oral administration.
For patients receiving multiple medicines during transplantation and recovery, managing interactions and maintaining adherence can be particularly challenging. The choice of prophylactic therapy must therefore account for the patient’s clinical condition, concurrent treatments, infection risk, and ability to tolerate the prescribed regimen.
Rezafungin is being investigated in ReSPECT as a once-weekly intravenous option. The study regimen involved a 400 mg intravenous loading dose on Day 1, followed by 200 mg once weekly.
By comparison, the standard antimicrobial regimen consisted of a daily oral azole, either fluconazole or posaconazole, together with trimethoprim/sulfamethoxazole following engraftment.
The difference in administration schedules is relevant when evaluating the practical characteristics of the regimens. Once-weekly intravenous administration may offer an alternative to daily oral antifungal prophylaxis for selected patients, although its suitability will depend on individual clinical circumstances, treatment protocols, and future regulatory guidance.
The ReSPECT findings contribute to ongoing efforts to evaluate different approaches to preventing fungal infections in this medically vulnerable population.
Researchers Highlight the Importance of New Clinical Evidence
Johan Maertens, MD, PhD, of University Hospitals Leuven, highlighted the continuing need to improve prevention strategies for patients undergoing allogeneic stem cell transplantation.
“Patients undergoing allogeneic haematopoietic stem cell transplantation remain vulnerable to invasive fungal disease, and prevention is an important part of their clinical management. ReSPECT provides new Phase III evidence in this complex setting and contributes to the continuing effort to address unmet needs in antifungal prophylaxis,” Maertens said.
His comments underscore the importance of generating robust clinical evidence in transplant medicine, where patients face multiple risks related to immunosuppression, infection, and treatment-related complications.
Yuri Martina, MD, PhD, Chief Development and Medical Officer at Mundipharma, also highlighted the company’s continued investment in rezafungin research.
“Our continued investment in the rezafungin research programme reflects Mundipharma’s commitment to advancing antifungal science and generating robust clinical evidence in areas where important unmet needs remain,” Martina said.
He described ReSPECT as an important part of the company’s research programme and welcomed the presentation of the additional Phase III findings to the scientific community at IDWeek 2026.
Martina also outlined plans to communicate research progress and emerging findings through international scientific meetings, including the American Society of Hematology (ASH), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the European Hematology Association (EHA), Trends in Medical Mycology (TIMM), and the European Society for Blood and Marrow Transplantation (EBMT).
The company also plans to share findings through peer-reviewed publications in specialised medical journals.
According to Martina, submission of the ReSPECT data to the FDA and EMA represents another milestone in the ongoing development programme.
Regulatory Review and Current Approval Status
Mundipharma has submitted data from the ReSPECT programme to the FDA and EMA for regulatory review. In the United States, the FDA has granted Priority Review for the investigational use of rezafungin for antifungal prophylaxis in adults undergoing allo-HSCT, with a PDUFA target action date in the first quarter of 2027.
Priority Review is a regulatory designation intended to expedite the review of applications for medicines that, if approved, may offer significant improvements in the treatment, diagnosis, or prevention of serious conditions. The designation does not guarantee approval.
REZZAYO already has approved indications for the treatment of invasive candidiasis, but these indications are distinct from the prophylaxis use being evaluated in ReSPECT.
In the United States, REZZAYO is indicated for the treatment of candidemia and invasive candidiasis in adult and paediatric patients aged 12 years or older who have limited or no alternative treatment options. The approval is based on limited clinical safety and efficacy data.
In the European Union, REZZAYO is indicated for the treatment of invasive candidiasis in adults. Its European product information also advises consideration of official guidance regarding the appropriate use of antifungal agents.
The investigational use of rezafungin to prevent invasive fungal disease in adults undergoing allo-HSCT is not currently an approved indication in either the United States or the European Union. Any future approval will depend on the relevant regulatory authorities’ assessment of the submitted evidence.
The additional Phase III ReSPECT findings provide further detail on the efficacy, endpoint components, and safety of rezafungin for antifungal prophylaxis following allogeneic stem cell transplantation.
The study met its primary endpoint by demonstrating non-inferiority to the standard antimicrobial regimen for fungal-free survival at Day 90. The additional analyses were consistent with the topline findings, and no new safety signals were identified in the allo-HSCT population.
With the data submitted to the FDA and EMA, rezafungin’s potential role in antifungal prophylaxis is now under regulatory review. The FDA’s Priority Review designation and anticipated first-quarter 2027 target action date represent important milestones in the programme.
For Mundipharma, the findings support continued investigation of rezafungin as a potential option for preventing invasive fungal disease in adults undergoing allo-HSCT. Until regulatory review is completed, however, this prophylaxis use remains investigational.
The ongoing research programme, future scientific presentations, and peer-reviewed publications are expected to provide additional information as the company continues to evaluate rezafungin’s potential role in addressing the clinical challenges associated with invasive fungal disease prevention.
About Mundipharma
Mundipharma is a global healthcare company with a presence in Africa, Asia Pacific, Canada, Europe, Latin America and the Middle East. In line with its mission, United for Patients, Mundipharma is dedicated to bringing innovative treatments to patients in the areas of pain management, infectious disease, ophthalmology, oncology, respiratory and central nervous system. For more information visit: www.mundipharma.com.