Allergan has won US approval for its fixed-dose combination antibiotic Avycaz in a new indication, becoming the first new drug to treat pneumonia caused by Gram-negative bacterial infections in more than 15 years.
The FDA approved Avycaz for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults caused by range of Gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
The company said that the approval is important as some types of Gram-negative bacteria have become increasingly resistant to available antibiotics, resulting in increased illness and death as well as contributing to escalating healthcare costs.
The approval is on the back of phase III data from a trial in 870 patients who were randomised to receive either Avycaz 2.5g or meropenem 1g intravenously every eight hours for 7 to 14 days of therapy. Avycaz proved non-inferior to meropenem on 28-day all-cause mortality, with rates of 9.6% and 8.3% respectively.
Originally developed by Actavis (which was acquired by Allergan in a $25bn deal in 2014), Avycaz combines established cephalosporin antibiotic ceftazidime with avibactam, a novel beta lactamase inhibitor that helps tackle resistance. The drug was approved in 2015 for complicated intra-abdominal and urinary tract infections and brought in $43m in sales for Allergan in the first nine months of 2017.
The antibiotic is sold in Europe by Pfizer under the Zavicefta brand name and got a green light from the EMA in 2016. The antibiotic was one of the products sold by AstraZeneca to Pfizer that year in a deal valued at $550m upfront. Zavicefta is already approved in Europe for HABP/VABP.
One of the key roles for the new product is in the treatment of infections with carbapenem-resistant Enterobacteriaceae (CRE). Carbapenems such as meropenem, ertapenem, imipenem and doripenem are normally reserved for serious infections caused by drug-resistant Gram-negative bacteria, but rates of resistance to these drugs are on the rise and pose a serious threat to public health.
In 2014, a review on antimicrobial resistance warned that the loss of efficacy of antibiotics could result in 10 million extra deaths a year by 2050 if action is not taken, with the cost associated with resistance hitting $100tn by that date.
“Healthcare providers in the US have not had access to a new treatment option for patients with HABP/VABP due to Gram-negative bacteria in over 15 years,” said David Nicholson, Allergan’s head of R&D.
“Gram-negative pathogens are some of the most pressing antibiotic resistance threats and cause more than 40,000 resistant infections in the US annually.”