• 21 May 2024
• Admin
• News Article

Zai Lab and Innoviva Announce NMPA Approval for XACDURO

Zai Lab and Innoviva Specialty Therapeutics Announce NMPA Approval for XACDURO® (Sulbactam-Durlobactam or SUL-DUR) for Hospital-Acquired and Ventilator-Associated Pneumonia Caused by Acinetobacter Baumannii-Calcoaceticus Complex in China

Overview

Drug-resistant Acinetobacter baumannii is a growing global health threat and high priority pathogen needing new antibiotics, according to World Health Organization
China NMPA approval based on comprehensive clinical data demonstrating robust activity of SUL-DUR against carbapenem-resistant bacterial strains

Acinetobacter Infections in China

• In China, it is estimated there are approximately 300,000 cases of Acinetobacter infections and approximately 74% of them are carbapenem-resistant  Zai Lab Limited and Innoviva Specialty Therapeutics today announced that China’s National Medical Products Administration (NMPA) has approved Zai Lab’s New Drug Application (NDA) for XACDURO® (sulbactam-durlobactam) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex in patients 18 years of age and older. 
• The World Health Organization considers Acinetobacter a top-priority pathogen worldwide that needs novel antibiotics1. 
• The NMPA approval of XACDURO demonstrates Zai Lab’s commitment to developing and delivering innovative therapies that address high unmet medical needs for patients in China and around the world, said Dr. Harald Reinhart, President and Head of Global Development, Neuroscience, Autoimmune & Infectious Diseases, Zai Lab. 
• “The public threat of dangerous pan-resistant Acinetobacter infections requires urgent action, as treatment options are limited and mortality rates remain high. We believe XACDURO represents a major step forward in an area of significant patient need.”

NMPA Approval of XACDURO

• The NMPA approval of XACDURO in China is based on positive results from the ATTACK trial (NCT03894046), a global, Phase 3 registrational trial evaluating the safety and efficacy of XACDURO versus colistin in patients with infections caused by A. baumannii. 
• In the pivotal study, XACDURO demonstrated statistical non-inferiority versus colistin for the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter infections and a statistically significant improvement in clinical cure rates. 
• XACDURO was well tolerated and exhibited a favorable safety profile across the clinical program.
• Zai Lab participated in the global ATTACK study by enrolling patients in China. 
• The Chinese patient cohort data confirm the findings of the global study regarding mortality and clinical response improvement.

Regardng Approval

In May 2023, Innoviva Specialty Therapeutics announced that the U.S. Food and Drug Administration (FDA) approved XACDURO for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex – the first such FDA-approved pathogen-targeted therapy.

From Innoviva Specialty Therapeutics on Infections

• “Six years ago, our two companies shared the vision of creating an innovative antibiotic therapy that could effectively address the global rise of drug-resistant Acinetobacter-related infections,” said Matt Ronsheim, PhD, President of Innoviva Specialty Therapeutics. 
• “This approval is a testament to our strong and successful partnership with Zai Lab. Their invaluable collaboration during the Phase 3 trials provided the crucial data needed to move XACDURO through the regulatory process in China, just one year after it was approved in the U.S.”

About XACDURO® (sulbactam-durlobactam)

• XACDURO® (sulbactam-durlobactam) is an intravenous drug developed by Entasis Therapeutics Inc., an affiliate of Innoviva Specialty Therapeutics, which is a combination of sulbactam, a β-lactam antibiotic, and durlobactam, a β-lactamase inhibitor, or BLI. 
• XACDURO has been approved in the United States and mainland China for the treatment of adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. 
• Zai Lab has an exclusive license to develop and commercialize XACDURO in Greater China (mainland China, Hong Kong, Taiwan and Macau, collectively), Korea, Vietnam, Thailand, Cambodia, Laos, Malaysia, Indonesia, the Philippines, Singapore, Australia, New Zealand and Japan.

About Acinetobacter Baumannii

• Members of the Acinetobacter baumannii-calcoaceticus complex (Acinetobacter) are Gram-negative, opportunistic human pathogens that predominantly infect critically ill patients and often result in severe pneumonia and bloodstream infections.1 
• They can also infect other body sites, such as the urinary tract and the skin. 
• Acinetobacter is considered a global threat in the healthcare setting due in part to its ability to acquire multidrug resistance. 
• Acinetobacter is resistant to penicillins and has also acquired resistance genes for almost all antibiotics used to treat Gram-negative bacteria, including fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems.

CDC on Urgent Threat

• The Centers for Disease Control and Prevention (CDC) has identified carbapenem-resistant micro-organisms as an urgent threat.
• Globally, Acinetobacter baumannii was among the top six leading pathogens for deaths associated with resistance in 2019.
• Carbapenem-resistant Acinetobacter is considered a Priority 1 pathogen by the World Health Organization (WHO).

Epidemiology: Acinetobacter

• In the U.S., there are an estimated 40,000 to 80,000 cases of Acinetobacter each year, and about 40 percent of those are carbapenem-resistant Acinetobacter.
• Globally, there are about a million cases each year of Acinetobacter, and about two-thirds of those are carbapenem-resistant Acinetobacter baumannii.
• More than 300,000 global deaths annually are associated with carbapenem-resistant Acinetobacter7.

About Acinetobacter Baumannii Infections in China and Eastern Asia

• Based on the 2022 Annual Report of CARSS (China Antimicrobial Resistance Surveillance System), approximately 300,000 Acinetobacter infections were reported in mainland China. 
• According to the most recent CHINET report, resistance of Acinetobacter baumannii to the carbapenem class of antibiotics has risen to approximately 74% in China. 
• Acinetobacter is also the most common pathogen that leads to hospital-acquired pneumonia and ventilator-associated pneumonia in China. 
• With commercially available therapy, the mortality rate is estimated to be 38% in China and 43% in Eastern Asia.
• XACDURO® INDICATION & USAGE FROM U.S. PRESCRIBING INFORMATION

Indication

XACDURO (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use is indicated in adults for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii- calcoaceticus complex.

Limitations of Use

XACDURO is not indicated for the treatment of HABP/VABP caused by pathogens other than susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of XACDURO and other antibacterial drugs, XACDURO should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

IMPORTANT SAFETY INFORMATION FROM U.S. PRESCRIBING INFORMATION

Contraindications: 

XACDURO is contraindicated in patients with a history of known severe hypersensitivity to the components of XACDURO or other beta-lactam antibacterial drugs.

Warnings and Precautions:

 Hypersensitivity was observed in patients treated with XACDURO in clinical trials. 

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. 
Before initiating therapy with XACDURO, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other beta lactams, and other allergens. If an allergic reaction occurs, discontinue XACDURO.

 Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. 

Evaluate if diarrhea occurs. If CDAD is suspected or confirmed, the risk/benefit of continuing treatment with XACDURO should be assessed.
Prescribing XACDURO in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse Reactions: The most common adverse reactions reported in >10% of patients treated with XACDURO were liver test abnormalities (19%), diarrhea (17%), anemia (13%), and hypokalemia (12%).