LONDON – A European initiative to tackle the rising tide of antibiotic resistance has kicked off, with GlaxoSmithKline plc putting up a Phase IIa compound as the first that will be advanced in clinical development as part of the public-private program.

Two other clinical-stage compounds owned by AstraZeneca plc also are candidates for further development as part of a €223.7 million (US$280.9 million) cooperative effort, "New Drugs for Bad Bugs," which aims to speed up delivery of new antibiotics.

The five pharma companies taking part will contribute €114.7 million through in-kind contributions, while €109 million will be in the form of European Commission grants to biotechs and academic groups that were invited to submit proposals on how they can contribute to particular aspects of clinical development when the call opened last week.

It is anticipated that further calls in the program will bring total spending to €600 million. "New Drugs for Bad Bugs" is part of the wider €2 billion 10-year Innovative Medicines Initiative, funded 50-50 by the European Commission and the industry to address bottlenecks in the drug development process.

After years of discussions about the need for an antibiotics program, Richard Bergström, director-general of the European Federation of Pharmaceutical Industries and Associations (EFPIA), said he was pleased to see the project get off the ground. "It's such a great thing that companies are saying they want to pool knowledge, and there is public-private co-funding," he told BioWorld Today.

Launching the call last week, Seamus O'Brien, executive clinical director at London-based AstraZeneca, said antibiotic research has become a "societal issue" with the emergence and spread of resistant bacteria leading to increased mortality and rising costs. A combined effort is needed because antibiotic R&D is different from other fields.

"The science is tricky; there are unique scientific bottlenecks, especially for Gram-negative bacteria, and there are challenges getting the agent to the target," O'Brien said.

In addition, there is a challenging regulatory environment with large studies required, and a low return on investment because antibiotics need to be used sparingly to protect against the emergence of resistance. It takes 10 years or longer to develop a new antibiotic, but the clonal spread of resistance can render a drug ineffective over wide areas – and commercially impaired – within months.

The difficulty in the antibiotics space has shrunk the number of players over the years. While there were 18 pharma companies active in the field in the early 1990s, only four are involved now.

O'Brien said the industry needs to discover new targets, find better ways to get agents to targets and map out new regulatory pathways. "Information sharing is fundamental to this program. We have to get better as an industry, to share success and failure, so we don't make the same mistakes twice."

Bergström agreed. "We need to send a big signal to everyone to say, 'Get back into this field.' For SMEs and academics, there is money, and this is a huge opportunity for small biotechs," he said.

The "New Drugs for Bad Bugs" project is part of a wider European Commission program to halt the spread of antibiotic resistance, announced in November. In addition to funding development of new antibiotics, it aims to ensure they are used appropriately and to improve infection control. (See BioWorld International, Nov. 23, 2011.)

Apart from sharing failures – so that other people do not waste time on fruitless research – "New Drugs for Bad Bugs" will sponsor biomarker research and the development of rapid diagnostics, enabling fast recruitment of likely responders to clinical trials. It also will promote the formation of clinical trials consortia to conduct trials in areas where there are high levels of resistant bacteria. Another research theme will concentrate on creating the ability to rationally design compounds that can penetrate Gram-negative bacteria.

The antibiotic that will be the first subject of the cooperative approach to clinical development is GSK1322322, a small-molecule inhibitor of peptide deformylase. That compound has shown good in vitro activity against methicillin-resistant Staphylococcus aureus and drug-resistant strains of pneumococcus, has no cross-resistance with existing antibiotics and has completed Phase I and Phase IIa.

Following that program, AstraZeneca has made an outline commitment to put a MedImmune monoclonal antibody, MEDI4893, against S. aureus, and AZD9773, a polyclonal antibody against tumor necrosis factor for treating septic shock, into the project.

Alongside GSK and AstraZeneca, the other pharma companies taking part in the program are Johnson & Johnson, Sanofi SA and Basilea Pharmaceutica Ltd.

"We've vacuum-cleaned what's around and agreed to co-fund projects," Bergström said. "We will pool knowledge from companies that have left the field and compounds that have been left on the shelf and disseminate all that information."