But it seems the industry has passed a tipping point; when the weight of evidence, government reports and warnings from experts and learned societies - as well as the promise of financial incentives for companies - has created enough impetus to spur companies into action.
In the UK there have been several reports that have made the case that the overuse of antibiotics is driving resistance and is making
infectious disease treatments less effective. Until recently, solutions to the problem of antimicrobial resistance, and in particular new treatments coming through the pipeline, have been scarce. The Government’s UK Review on Antibacterial Resistance, led by Jim O’Neill, identified a lack of funding as a major issue that prevents pharma companies from investing in research into new antibiotics.
It found: “In researching our latest report, we found no shortage of ideas, and promising new technologies. But progress is too slow due to lack of investment, and much of the workforce is edging towards retirement. New drugs take 10 to 15 years to come onto market. The time for action is now.”
Global coalitions to tackle AMR
The R&D community has heeded the call. In June, Pharmafocus attended with world experts who gathered at the Wellcome Trust in London to launch Antibiotic Discovery Global – a powerful coalition of world experts that are joining forces to tackle the dual crises of antimicrobial resistance and the previously-empty antibiotic development pipeline, by supporting global antibiotic discovery and rejuvenating older antibiotics for new uses. The network will also support the need for a global antimicrobial resistance innovation fund, as was proposed by the third interim report from the O’Neill Review.
There’s evidence that the UK appears to be stepping up to the challenge. According to a joint report by the intellectual property management specialist CPA Global, and the intellectual property firm Marks & Clerk, the UK files the most patents in this area of any country in Europe, having filed 26 out of 332 global patents.
The research is a study undertaken as part of the Longitude Prize, a £10 million prize fund aiming to revolutionise worldwide healthcare and conserve current antibiotics for future generations. It is run by the innovation charity Nesta with the UK’s innovation agency, Innovate UK, as funding partner.
UK leading the way on patents
The report shows that the UK is second only to the USA in the number of first fillings for patent applications directed to point-of-care diagnostics tests since 2009. Of the patent applications that specified which kind of antigen the test sought to detect, 134 were targeted at bacteria and 114 were targeted at viruses. Only seven were targeted at infectious parasites and five at fungi.
The most commonly targeted disease-causing antigens were mycobacteria (a cause of tuberculosis – with 28 applications), HIV (nine applications), methicillin resistant Staphylococcus aureus (MRSA), (with eight applications) and Clostridium difficile (which had nine applications).
The European picture
Across the continent, the European Society of Clinical Microbiology and Infectious Disease (ESCMID) has warned that Europe collectively could face more than a million deaths in an impending ‘antibiotic armageddon’, unless much more is done to develop new cures, rapid diagnostics and preventative measures to combat the spread of drug resistant diseases.
Their experts warn that without more R&D money being spent on developing new drugs and the rationing of existing supplies, deaths across Europe from these infections could pass the grim milestone of a million by 2025. In Britain alone an estimated 10,000 people die a year – with predictions that this number could triple or even quadruple within the next 10 years.
Currently the best available figures were published back in 2009 and estimated that between 25,000 and 30,000 Europeans die each year due to antimicrobial resistance, and the total number of deaths is now over 400,000. Updated figures from the European Centre for Disease Prevention and Control (ECDC) will be available later this year.
And Professor Murat Akova, the president of ESCMID, says: “Although we could see European national numbers remain broadly the same, it is far more likely to double, treble or even quadruple in the next 10 years. We need both European-wide and global strategies, as well as national initiatives, as the problem will not remain regionalised for long”.
Europe could be hit hard, with the estimated global economic costs associated with the problem reaching $100 trillion, potentially resulting in a significant reduction in GDP of 2-6% depending on the estimate, with the poorest countries projected to experience the largest relative loss in GDP.
The economic cost in Europe is already approximately €1.5 billion and rising. Akova adds: “Focusing only on the death toll by antimicrobial resistance obfuscates the gigantic problem of not being able to offer patients many of the modern healthcare victories. The rapid increase in antimicrobial resistance in Europe and the world is jeopardising modern healthcare. And resistance is spreading to the UK from across other European nations.”
Companies ramping up new drugs
In response, some firms are taking action now. Roche is teaming up with two antibiotic specialists, Japan-based pharma firm Meiji and Canadian Fedora, to tackle bacterial resistance.
And Actavis and AstraZeneca have both had new anti-infectives approved by the FDA in 2015. Next in line is Merck’s Sivextro (tedizolid phosphate), which Merck launched in June and is the first new drug in its class of antibiotics in the UK in almost 15 years, which is approved to treat acute bacterial skin and skin structure infections (ABSSSI).
Similarly, the Swiss firm Basilea also launched Zevtera (ceftobiprole medocaril) in June for the first-line treatment of serious bacterial pneumonia. Zevtera is the only antibiotic approved as a monotherapy in the UK for the treatment of community-acquired and hospital-acquired pneumonia that is effective against MRSA infections and gram-negative pathogens such as strains of Pseudomonas aeruginosa and enterobacteriaceae.
In July Basilea had its investigational anti-fungal, isavuconazole, recommended by the EMA for the treatment of invasive aspergillosis and mucormycosis in adults. The European Commission’s sign-off of the EMA’s advisory committee’s decision is due to be completed later in 2015.
Combination of carrot and stick
Dr Achim Kaufhold, who is chief medical officer at Basilea, says that the pharma industry will need flexibility and more support from regulators when approving new anti-infectives to help tackle antimicrobial resistance.
“It’s encouraging to see that regulators have recently taken steps to recognise some of the challenges companies have historically faced in bringing new anti-infectives to market,” he says.
“For example, for some infections such as those due to multi-drug resistant pathogens, the enrolment of appropriate patients into clinical trials can be challenging. Recently both the FDA and the EMA seem to be more open to more streamlined drug development pathways. This includes the reduction of total patient numbers, in certain circumstances, by allowing the use of external controls versus the use of traditional controlled, randomised trials.”
This more flexible approach may already be bearing fruit. Globally, research by the International Federation of Pharma Manufacturers and Associations (IFPMA) into anti-infective R&D shows that pharma companies are currently working on 34 antibacterial compounds (19 molecules and 15 vaccines), of which eight are in Phase III trials.
The IFPMA has identified that a combination of push and pull mechanisms are needed to move research forward and help ‘de-risk’ companies’ initial investments by pooling funds and expertise.
They say push mechanisms should include R&D funding grants, public-private partnerships to help de-risk initial investment by sharing cost and pooling expertise, and tax credits to increase the return on investment of successful medicines by subsidising the huge costs of R&D through the reduction of tax liability - although this latter mechanism tends to mostly appeal to bigger pharma firms.
And pull mechanisms should also include one-off prizes for any successful new developments and extended patent exclusivity, to create additional incentives for pharmaceutical companies to make the significant R&D investments required.
Their report - Rethinking the way we fight bacteria - concludes that concerted action is needed to ensure the global pool of effective antibiotics remains viable for a longer period, and to boost antibiotic development.
This is summed up by Mario Ottiglio, who is director of public affairs, communications and global health policy at the IFPMA, who says: “The slowdown of new antibiotic approvals is the tip of the iceberg; actions are needed from basic research, and pharmaceutical R&D, to regulatory requirements and clinical use.”
The pharma industry has a responsibility to lead the fight against antimicrobial resistance. But it will take a radical shift in thinking, and also support from governments, drug regulators, charities, healthcare professionals and the public.
As Mario Ottliglio says: “A robust pipeline of new antibiotics will not be sufficient to address antimicrobial resistance to drugs without ensuring the increasing awareness that these medicines should also be prescribed appropriately and used properly. Rethinking the way we fight bacteria is a shared responsibility that belongs to everybody.”
More Information on Pharmafile