ContraFect Provides Update from the Futility Analysis of the Phase 3 DISRUPT Study of Exebacase

Rhea-AI Summary

ContraFect Corporation (CFRX) announced the database lock of its Phase 3 DISRUPT study for exebacase targeting Staph aureus bacteremia. An interim futility analysis highlighted a clinical response of 52.7% in the exebacase arm versus 58.6% in the placebo arm. The study's enrollment was halted due to insufficient conditional power. Despite a promising safety profile, CEO Roger Pomerantz indicated the trial results are 'uninterpretable' due to unexpected responses in the placebo group. The company plans further studies and aims to initiate a Phase 1b/2 study in early 2023.

Positive

• Successful database lock of Phase 3 DISRUPT study.
• Plans for future studies, including a Phase 1b/2 study in early 2023.
• Strong safety profile noted in the study.

Negative

• Interim futility analysis resulted in the recommendation to stop enrollment.
• Clinical response in the exebacase arm was lower than expected compared to the placebo arm.
• Uninterpretable results due to unprecedented placebo responses.

Take the Deep Dive in a Virtual Fireside Chat to be Held in Q1 2023

YONKERS, N.Y., Dec. 19, 2022 (GLOBE NEWSWIRE) -- ContraFect Corporation (Nasdaq: CFRX), a clinical-stage biotechnology company focused on the discovery and development of direct lytic agents (DLAs), including lysins and amurin peptides, as new medical modalities for the treatment of life-threatening, antibiotic-resistant infections, today announces the database lock of its Phase 3 DISRUPT (Direct Lysis of Staph aureus Resistant Pathogen Trial) study of exebacase in patients with Staph aureus bacteremia, and a summary of the topline data and the preliminary findings from its own analysis of data from the interim futility analysis (the Futility Dataset). All patients in the DISRUPT study have now been independently adjudicated and the study database has been locked. The blinding and data integrity of the study was maintained throughout, enabling the company to not only share the Futility Dataset, but also to utilize the results of the study, including the safety data, in future regulatory filings for exebacase.

The interim futility analysis was conducted, as planned, when approximately 60% of the primary endpoint population, patients with methicillin-resistant S. aureus (MRSA) bacteremia, had been randomized and followed for 14 days after treatment. The results below from the Futility Dataset and the company’s own analysis were generated based on the clinical response of the primary endpoint, at day 14 in 84 MRSA bacteremia patients, of which 55 patients were treated with exebacase plus standard of care (SOC) antibiotics (the Exebacase Arm) and 29 patients were treated with placebo plus SOC antibiotics (the SoCA Arm).

• Clinical response at day 14 was 52.7% in the Exebacase Arm (n=55) compared to 58.6% in the SoCA Arm (n=29).
• The two arms were well balanced in most baseline factors including final diagnosis, primary source of infection, risk factors for bacteremia, SOC antibiotic used and age.
• There was an imbalance in the baseline disease severity of patients, as determined by the APACHE II score, with 34.8% of patients in the Exebacase Arm having an APACHE II score >15 at randomization, as compared to only 13.8% of patients in the SoCA Arm. A patient with an APACHE II score above 15 is considered to have an extremely poor prognosis and a significantly increased risk of mortality.
• Subgroup analyses of clinical response were all as expected, based on the topline results, other than APACHE II subgroups.
• Proper study randomization and drug allocation was confirmed by pharmacokinetic data.
  

“The unprecedented clinical response in the placebo arm of this study, which is nearly double the response rate observed in our Phase 2 study of exebacase and in comparable Phase 3 studies of daptomycin and fosfomycin, coupled with the conduct of the study during the COVID pandemic, leaves us with trial results that are uninterpretable,” said Roger J. Pomerantz, MD, President, Chief Executive Officer, and Chairman of ContraFect. “However, the importance of completing the full study in a blinded, placebo-controlled manner cannot be understated. The full results, which will be coming in the first quarter, including the safety database, will be used as part of any future regulatory submissions for the approval of exebacase. We believe, given the response rates and strong safety profile observed in our studies to date, that another study in this patient population should be conducted in the future by us or a partner.”

“While we look forward to repeating this study in Staph bacteremia in the future, we remain keenly focused on our near-term opportunities to significantly improve patient outcomes in serious infectious diseases. We are poised to start dosing patients early in the first quarter of the new year in our Phase 1b/2 study of patients with chronic prosthetic joint infections of the knee, using intra-articular exebacase, with which we have seen promising effects in a significant group of compassionate use patients. In addition, we remain on track to initiate a Phase 1 study of CF-370, our first engineered lysin targeting Gram-negative pathogens, in the second quarter of 2023,” added Garrett Nichols, MD, ContraFect’s Interim Chief Medical Officer.

The Phase 3 DISRUPT study of exebacase is a randomized, double-blind, placebo-controlled clinical study conducted in the United States in 259 of the planned 348 patients with S. aureus bacteremia, including right-sided endocarditis. Enrollment in the trial was stopped following a review of the pre-specified, interim futility analysis by the independent Data Safety Monitoring Board (DSMB). The DSMB recommended the trial be stopped because the conditional power of the trial was below the pre-specified threshold for futility as per the DSMB charter. No safety concerns were noted by the DSMB. All patients have completed all study visits, and all patient outcomes have been verified by the blinded adjudication committee. The full results and the clinical study report are expected in the first quarter of 2023. The company is planning a virtual fireside chat in the first quarter of 2023 for an in-depth review and discussion of the DISRUPT study.

About ContraFect:

ContraFect is a biotechnology company focused on the discovery and development of DLAs, including lysins and amurin peptides, as new medical modalities for the treatment of life-threatening, antibiotic-resistant infections. An estimated 700,000 deaths worldwide each year are attributed to antimicrobial-resistant infections. We intend to address life threatening infections using our therapeutic product candidates from our platform of DLAs, which include lysins and amurin peptides. Lysins are a new class of DLAs which are recombinantly produced antimicrobial proteins with a novel mechanism of action associated with the rapid killing of target bacteria, eradication of biofilms and synergy with conventional antibiotics. Our DLAs exhibit broad-spectrum activity against a wide range of antibiotic-resistant Gram-negative pathogens, including P. aeruginosa, Acinetobacter baumannii, and Enterobacter species. We believe that the properties of our lysins and amurin peptides will make them suitable for targeting antibiotic-resistant organisms, such as MRSA and P. aeruginosa, which can cause serious infections such as bacteremia, pneumonia and osteomyelitis. We have completed a Phase 2 clinical trial for the treatment of Staph aureus bacteremia, including endocarditis, with our lead lysin candidate, exebacase, which is the first lysin to enter clinical studies in the U.S. Exebacase was granted Breakthrough Therapy designation by the FDA for the treatment of MRSA bloodstream infections, including right-sided endocarditis, when used in addition to SOC anti-staphylococcal antibiotics.

Follow ContraFect on Twitter @ContraFectCorp and LinkedIn.

This project has been supported in whole or in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50121C00021.

Forward-Looking Statements:

This press release contains, and our officers and representatives may make from time to time, “forward-looking statements” within the meaning of the U.S. federal securities laws. Forward-looking statements can be identified by words such as “projects,” “may,” “will,” “could,” “would,” “should,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “potential,” “promise” or similar references to future periods. Examples of forward-looking statements in this release include, without limitation, statements regarding the interim futility analysis, study data and analyses regarding the same, database lock, patient adjudication, statements made by Dr. Pomerantz, timing and expectations regarding full DISRUPT study results, the Phase 1b/2 prosthetic joint infection study, the Phase 1 study of CF-370 and the fireside chat, statements made by Dr. Nichols, ContraFect’s ability to discover and develop DLAs as new medical modalities for the treatment of life-threatening, antibiotic-resistant infections, whether ContraFect will address life-threatening infections using therapeutic candidates from its DLA platform, whether lysins are a new class of DLAs which are recombinantly produced, antimicrobial proteins with a novel mechanism of action associated with the rapid killing of target bacteria, eradication of biofilms and synergy with conventional antibiotics, whether ContraFect’s DLAs which exhibit broad-spectrum activity against a wide range of antibiotic-resistant Gram-negative pathogens, and whether the properties of ContraFect’s DLAs will make them suitable for targeting antibiotic-resistant organisms, such as MRSA and P. aeruginosa. Forward-looking statements are statements that are not historical facts, nor assurances of future performance. Instead, they are based on ContraFect’s current beliefs, expectations and assumptions regarding the future of its business, future plans, strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent risks, uncertainties and changes in circumstances that are difficult to predict and many of which are beyond ContraFect’s control, including, without limitation, that ContraFect has and expects to continue to incur significant losses, ContraFect’s need for additional funding, which may not be available, the occurrence of any adverse events related to the discovery, development and commercialization of ContraFect’s product candidates such as unfavorable clinical trial results, insufficient supplies of drug products, the lack of regulatory approval, or the unsuccessful attainment or maintenance of patent protection, changes in management may negatively affect ContraFect’s business and other important risks detailed under the caption “Risk Factors” in ContraFect's Quarterly Report on Form 10-Q for the quarter ended September 30, 2022 and its other filings with the Securities and Exchange Commission. Actual results may differ from those set forth in the forward-looking statements. Any forward-looking statement made by ContraFect in this press release is based only on information currently available and speaks only as of the date on which it is made. Except as required by applicable law, ContraFect expressly disclaims any obligations to publicly update any forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

Investor Relations Contacts:

Michael Messinger
ContraFect Corporation
Tel: 914-207-2300
Email: mmessinger@contrafect.com

FAQ

What were the results of the DISRUPT study for CFRX?

The DISRUPT study showed a clinical response of 52.7% in the exebacase arm versus 58.6% in the placebo arm, leading to an interim futility analysis.

What is the significance of the Phase 3 DISRUPT study for ContraFect?

The study's results will contribute to future regulatory filings for exebacase, though the outcomes were deemed uninterpretable due to unexpected high responses in the placebo group.

When will full results from the DISRUPT study be available?

Full results and the clinical study report are expected in the first quarter of 2023.

What are ContraFect's next steps after the DISRUPT study?

ContraFect plans to conduct further studies on exebacase and start a Phase 1b/2 study for chronic prosthetic joint infections in early 2023.

What is CFRX's next study after the DISRUPT trial?

CFRX aims to initiate a Phase 1 study of CF-370, targeting Gram-negative pathogens, in the second quarter of 2023.