Cubist wins FDA nod for antibiotic Zerbaxa
This article was originally published in Scrip
Before its acquisition of Cubist Pharmaceuticals was barely underway, Merck's 9.5bn bid for the company already has garnered it a nice payoff – the US approval on 19 December of Zerbaxa (ceftolozane/tazobactam), a new combination antibiotic intended to treat adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI).
Shares of Cubist rose $2.08, or 2.1%, in after-hours trading on 19 December.
Merck also announced on 19 December it had begun its tender offer to acquire Cubist – a deal revealed on 8 December (scripintelligence.com, 9 December 2014).
Before Zerbaxa’s approval, Sagient Research's BioMedTracker, an affiliate of Scrip, had put the likelihood of the drug gaining the FDA's blessing at 93%, which was 5% above the average probability of US approval for the same indication based on the historical performance of medicines in the same development phase.
Zerbaxa consists of ceftolozane, a cephalosporin antibacterial drug, and tazobactam, a beta-lactamase inhibitor.
Specifically, Zerbaxa is indicated for use with metronidazole for adults with cIAI caused by Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius.
For the cUTI indication in adults, Zerbaxa is aimed at infections caused by pyelonephritis, caused by the following Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa.
Zerbaxa is the fourth new antibacterial with the QIDP designation to receive FDA approval.
The Infectious Diseases Society of America (IDSA) said Zerbaxa's approval signifies several "significant milestones in the battle against antibiotic-resistant superbugs."
The drug's clearance to enter the US market marks the halfway point in reaching IDSA's 2010 "10 x 20 Initiative" goal of 10 new systemic antibacterial drugs by 2020.
Zerbaxa also is the first of the five 10 x 20 antibiotics to address certain serious and resistant Gram-negative bacteria, IDSA said.
"The new antibiotic will provide doctors more options for treating complicated urinary tract and complicated intra-abdominal infections," the group said in a 19 December statement.
But even this important approval doesn’t address all of our antibiotic needs. Patients still face life-threatening infections for which additional new antibiotics are urgently needed. IDSA will continue to advocate for economic and regulatory incentives to help bring these new antibiotics to market, and for improved stewardship, data collection and diagnostics to ensure antibiotics are used appropriately.
Zerbaxa's new drug application, which was submitted to the FDA in April, was based on positive data from two pivotal Phase III trials of the combo antibiotic in cUTIs and cIAIs, with met the FDA's and the European Medicines Agency's specified primary endpoints (scripintelligence.com, 20 June 2014, 22 April 2014).
Results of the secondary analyses were consistent with and supportive of the primary outcomes, Cubist reported.
In the studies, Zerbaxa's demonstrated activity against problematic Gram-negative bacteria, including P aeruginosa and extended-spectrum beta-lactamase-producing E coli and Klebsiella pneumoniae in patients with complicated infections.
The drug also is being developed as a potential treatment for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) at a dose of 3g every 8 hours.
Zerbaxa's was designated by the FDA as a qualified infectious disease product (QIDP) in the cUTI, cIAI, HABP and VABP indications – a status under which the drug is eligible for an additional five years of market exclusivity if approved for the indications.
Drugs holding the QIDP status, which was created under the Generating Antibiotic Incentives Now (GAIN) Act in 2012 to provide incentives for drug makers to pursue antibiotic against some of the deadliest infections, receive special priority reviews intended to accelerate their regulatory process (scripintelligence.com, 5 June 2014, 10 July 2012, 19 July 2012).
The FDA has granted the QIDP designation at least 64 times to 43 unique molecular entities.
The FDA's approval of Zerbaxa, IDSA said, "is proof that the GAIN Act is having an impact."
Nonetheless, the group insisted more incentives are needed to ensure "a robust pipeline will be able to continue producing the antibiotics patients will need for years to come."