The Rise and Rise of Superbugs – so how do we fund superdrugs?

Richard Bax and Flic Gabbay

TranScrip Partners

TranScrip Partners’ Infectious Disease Specialists Flic Gabbay and Richard Bax share their view on bacterial resistance in our infectious diseases themed month.

In the last two months anxieties around the rise of bacterial resistance have been highlighted by governments and academia alike with the threat being compared to that of terrorism by The Chief Medical Officer of the United Kingdom1. It was the first time that the mainstream media recognised that controlling the threat of bacterial resistance could not simply be managed by limiting the use of antibiotics. Not only that, but pharmaceutical companies even given incentives may not be able to guarantee that we will have treatments in our medical armamentarium to combat the increasing numbers of superbugs.

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“It was the first time that the mainstream media recognised that controlling the threat of bacterial resistance could not simply be managed by limiting the use of antibiotics.”

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Earlier in March the annual meeting “Superbugs and Superdrugs – A Focus on Antibacterials” was held in London and later this month we will move on to ECCMID in Berlin where many of these topics will yet again be addressed.

At the “Superbugs” meeting there were 19 presentations attended by over 50 international attendees including big Pharma (Sanofi, Novartis, Astellas and J &amp, J), universities and small and medium sized Pharma (Rib-x, Evolva, Basilea, Affinium, Fidelta, Galapogos and Aquapharma Biodiscovery). Richard Bax (TranScrip Partners) helped organise and chaired the meeting.

In the first session he was joined by Richard Bergstrom, Director General of the European Federation of Pharmaceutical Industries and Associations (EFPIA), Line Matthiesen, Head of ID and Public Health Unit at the EU Commission, Ursula Theurtbacher, Centre for Anti-Infective Agents and between them they provided an Update on the Current R&amp,D and the Regulatory Environment. The public private initiatives were high on the agenda. New Drugs 4 Bad Bugs (ND4BB) is an EFPIA &amp, EU Commission “Innovative Medicine Initiative” (IMI) initiative in which big pharmaceutical companies, together with Small and Medium Enterprises (SMEs) jointly fund research and development initiatives projects to support the development of new antibiotics, particularly for the multidrug resistant Gram –ve organisms. In addition, the EU commission has called for FP-7 grant applications based on the call for activities on the diagnosis, use and R&amp,D of new antibiotics. The Centre of Anti-Infective Agents illustrated how such projects could be set up. The combined money for the two initiatives is in excess of £1.5 billion over the next few years. The success of the initiatives depends on how effectively the money can be distributed to support both early research programmes as well as those which reach the more expensive, clinical phases of development.

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“These funding “push” activities are indeed increasing, aiding new antibiotic R&amp,D but “pull” initiatives also need to become realities.”

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Other public or private funding agencies that act in this area include Wellcome Trust, NIAID, Gates Foundation and the Biomedical Advanced Research and Development Authority (BARDA).

These funding “push” activities are indeed increasing, aiding new antibiotic R&amp,D but “pull” initiatives also need to become realities. On both sides of the Atlantic such proposals include longer patent life and decreased regulatory processes because of the high medical need. A great deal of effort which has been summarised in Rex et al 2013 2 and is embodied in the principles of the GAIN Act3 and also in the keenly awaited further revision to the EMA guidelines4a, 4b has been put into designing clear and easier paths to registration. Hopefully these initiatives will increase the likelihood of regulatory success. Better regulatory predictability will drive a more certain market and allow more effective pricing as will the recognition of the high medical need for antibiotics effective against superbugs.

Recent post approval requirements in both EU and US, whilst becoming more extensive have also been designed with more effective collaboration with the appropriate agencies and to be achievable within a budget that does not further inhibit investments in antibiotic development. Early and limited registration may challenge post approval commitments in a way rarely seen in the past. The narrow indication proscriptive data sheets will require creative studies to police off-label use. Staged development of antibiotics, which may start as narrow spectrum and be developed for broader spectrum use, could result in complex and challenging discussions with regulators.

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“As big Pharma are more risk averse and rarely license technology early this will discriminate against the development of the truly novel antibiotics we need.”

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In the next few months documents from both EMA and FDA will be provided to offer further guiding principles to outline how the regulatory initiatives that have been widely discussed will be implemented.

Sadly, whilst such initiatives will help early academic research and companies with later stage products in clinical development, truly novel technologies (which always pose greater inherent risk) will struggle to raise money to get to the end of phase II. The current SME funding (predominantly angel and venture capital) is frequently inadequate to take companies through to the end of phase II when development money or license with big Pharma can continue their funding support. Big Pharma can fund this period for their own research programmes but SME Pharma cannot and, as was illustrated at Superbugs, and will be at ECCMID, there are numerous SME organisations with novel technologies. As big Pharma are more risk averse, and rarely license technology early, this will discriminate against the development of the truly novel antibiotics we need. Until we can address the translational development period in terms of funding and other support, potentially valuable antibiotics will fail in development regardless of how low are the barriers posed by the regulators.

References

1. Annual Report of the Chief Medical Officer, Volume Two, 2011 Infections and the rise of antimicrobial resistance, published Department of Health, 11th March 2013.

2. Rex J.R. et al, A Comprehensive Regulatory Framework to address the unmet need for new antibacterial treatments. The Lancet Infectious Diseases, Vol. 13 No. 3 pp 269-275.

3. GAIN Act (Generating Antibiotic Incentives Now) in Food and Drug Administration Safety and Innovation Act Title VIII 801-806 112TH CONGRESS 2D SESSION S.3187, US Congress 2012

4a. Guideline on the evaluation of medicinal products indicated for treatment of bacterial infections 15 December 2011 CPMP/EWP/558/95 rev 2 Committee for Medicinal Products for Human Use (CHMP)

4b. The Addendum to the above guideline (published for consultation until 31st January, 2013): Addendum to the note for guidance on evaluation of medicinal products indicated for treatment of bacterial infections (CPMP/EWP/558/95 REV 2) to address indication-specific clinical data, 21 June 2012 EMA/CHMP/776609/2011 Committee for Medicinal Products for Human Use (CHMP)

About the authors:

Richard Bax and Flic Gabbay have more than 30 years each working in anti-infective drug development and have both been involved in regulatory working parties in Europe and North America. Most recently Richard has been involved in presenting at the EMA workshop on the latest European guidance for antibiotic drug development. Richard and Flic are Senior Partners at TranScrip Partners a clinical and regulatory CRO which has been involved in the registration process of three successful recent antibiotic submissions and represents numerous companies with potential early and post approval stage antibiotics.

How can we support valuable antibiotic development?