Global concern that research and development to discover new antibiotics has languished in recent years has not escaped the attention of policymakers. The subject was high on the agenda at the meeting of G8 science ministers, who met in London June 12 ahead of the G8 summit in Northern Ireland.

With antimicrobial drug resistance seen as a major health security challenge, "we decided to act concertedly on developing the scientific input necessary to reduce antimicrobial resistance by working with existing agencies such as the World Health Organization," the science ministers said. Other important activities identified by the group include curbing the misuse of antibiotics, supporting targeted research to understand the development of resistance and developing diagnostics to better inform antimicrobial drug usage. The ministers also stated their support for international cooperation and sharing of surveillance data to improve global understanding of the spread of antimicrobial drugs resistance.

Warning Bells

The meeting comes at a time when warning bells have been sounded about the lack of new medicines to combat infections and replace those that are becoming ineffective. For example, in April, the Washington-based Infectious Diseases Society of America (IDSA) said, since it launched its 10 x '20 Initiative in 2010 (10 new antibiotics by 2020) the FDA has approved only one new systemic antibiotic.

And time is getting short to achieve that goal.

The IDSA's report identified only seven new drugs in Phase II or Phase III development for the treatment of infections caused by multidrug-resistant gram-negative bacilli bacteria. (See BioWorld Today, April 22, 2013.)

Further compounding the picture was a March report from the Centers for Disease Control and Prevention (CDC) that sounded an alarm about carbapenem-resistant Enterobacteriaceae (CRE), reporting that just in the first six months of 2012, nearly 200 hospitals and long-term acute care facilities in 42 states treated at least one patient infected with CRE.

Up to half of the patients who get bloodstream infections from CRE bacteria die. Besides spreading among patients, the CRE bacteria can transfer their resistance to other bacteria within their family, raising fears that the infections – so far confined to the health care setting – could spread into the community.

"Some progress has been made in the development of new antibiotics, but it's not nearly enough, and we absolutely must accelerate our efforts," said Henry Chambers, chair of IDSA's Antimicrobial Resistance Committee.

Also on the positive side of the ledger, the U.S. biotech industry is being encouraged to work on new antibiotics under the Generating Antibiotic Incentives Now (GAIN) provision of the FDA Safety and Innovation Act, which provides incentives for development of qualified infectious disease products, including antibiotic drugs for resistant pathogens. Under GAIN, companies will benefit by receiving priority review and qualifying drugs are eligible for designation as a fast-track product and for an additional five years of exclusivity.

Qualifying Organisms

The FDA recently published in the Federal Register a proposed list of qualifying organisms, including: Acinetobacter species, Aspergillus species, Burkholderia cepacia complex, Campylobacter species, Candida species, Clostridium difficile, Enterobacteriaceae, Enterococcus species, Mycobacterium tuberculosis complex, Neisseria gonorrhoeae, N. meningitidis, nontuberculous mycobacteria species, Pseudomonas species, Staphylococcus aureus, Streptococcus agalactiae, S. pneumoniae, S. pyogenes and Vibrio cholerae. Comments on the list are due by Aug. 12. (See BioWorld Today, June 13, 2013.)

On the research front, teams from Canada and the UK are working to find ways to combat antibiotic resistance. They are two years into a four-year funded program, designated the Canada/UK Partnership on Antibiotic Resistance, a collaboration between the Canadian Institutes of Health Research and the UK Medical Research Council.

The first team is led by Gary Dmitrienko, of the University of Waterloo, and Tim Walsh, of the University of Cardiff, and is focusing on hospital-acquired infections with the aim of developing a new treatment for infections caused by bacteria resistant to beta-lactam antibiotics like penicillin.

The second team involves Anthony Clarke, of the University of Guelph, who is working with Chris Dowson, of the University of Warwick (UK), studying bacterial cell walls in the search for new antimicrobial targets against which new drugs can be developed. The group is focusing on peptidoglycan, the key polymer that holds the bacterial cell wall together, in order to develop new targets and small-molecule probes that will inhibit peptidoglycan production and help kill the bacterium.

The G8 science ministers also will be encouraged by the fact that new biotech companies focusing on antibiotics are filling the void and getting support from venture capitalists.

Allecra Therapeutics GmbH, a Franco-German start-up, raised €15 million (U$19.6 million) in a Series A round to take two antibiotic development programs into the clinic and through clinical proof of concept.

The company is targeting hospital rather than community-acquired infections. "We're focused first of all on gram-negative multidrug-resistant bacteria, the highest unmet medical need within the antibiotic resistance area," Allecra co-founder and CEO Nicholas Benedict said.

And investor confidence is starting to return to the antibiotics arena.

Cempra Inc., for example, priced a public offering recently, selling 7.25 million shares at $7 each for gross proceeds of about $50.8 million. The company was able to leverage news of a successful end-of-Phase II meeting with the FDA, citing only the need for additional funding to proceed with the planned Phase III trial testing intravenous (I.V.)-to-oral administration of macrolide antibiotic solithromycin in community-acquired bacterial pneumonia. (See BioWorld Today, June 17, 2013.)

With regulatory filings expected later this year for antibiotic dalbavancin, Durata Therapeutics Inc. also padded its cash position. A month after securing a $20 million debt facility agreement, the Chicago-based biotech priced a $50 million public offering, selling 7.15 million shares at $7 apiece.

Proceeds will be used to support a new drug application in the U.S., and a marketing authorization application in Europe, expected by year-end, for dalbavancin, a long-acting intravenous lipoglycopeptide, for acute bacterial skin and skin structure infections.