Skepticism over new FDA taskforce for antibacterial development.
Skepticism over new FDA taskforce for antibacterial development
Prompted by a diminishing pipeline, the FDA has formed a new taskforce to support the development of antibacterial drugs. While this is a positive move, there are questions as to whether this is a serious refocus or simply another case of rehashing FDA guidances to produce unfeasible clinical trials that have previously caused promising – and effective – drugs to be lost or stuck in the pipeline.
The FDA reports that the Antibacterial Drug Development Task Force is a multi-disciplinary group of 19 Center for Drug Evaluation and Research (CDER) scientists and clinicians who will use existing partnerships and collaborations to work with other experts in the field. This includes teams from academia, industry, professional societies, patient advocacy groups, and government agencies. The taskforce’s role will be to identify priority areas and develop and implement possible solutions to the challenges of antibacterial drug development.
This will begin to sound familiar to anyone involved in the infectious diseases arena. The FDA has a long history of changing its mind and releasing different versions of guidances that many critics believe have made antibacterial clinical trials unfeasible. Clinical endpoints have changed, inferiority margins have been considered unattainable, and the requirement for patients not to have had pre-exposure to antibiotics has made patient recruitment near impossible (and, arguably, very unethical). In addition, these disappointing guidances were also issued after experts in the industry and antibacterial field had already been “consulted.”
As an example, the FDA admitted that it did not know how best to assess clinical trials for acute bacterial skin and skin structure infections (ABSSSIs) and the lack of clarity as to the FDA’s requirements had a knock-on effect on companies in the industry. Indeed, while the consultation process was taking place to redraft guidances for this indication, a number of drugmakers already had ABSSSI antibiotics part way through late-stage clinical trials, including Durata Therapeutics (dalbavancin), The Medicines Company (oritavancin), and Paratek Pharmaceuticals (PTK 0796).
The Medicines Company and Durata are both still in the process of completing further Phase III clinical trials after the FDA requested further non-inferiority data for both oritavancin and dalbavancin in 2008 and 2007, respectively. Paratek, meanwhile, lost its licensing partner for PTK 0796 after Novartis announced it was discontinuing development of the drug in July 2011. Consequently, developmental progress has been stunted for dalbavancin, oritavancin, and PTK 0796, all of which were once touted as promising drugs for the treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA).
It is hoped that the FDA’s new taskforce will be successful in revising guidance in antibacterial development, and that its formation is not just ticking another box as a requirement of the Generating Antibiotic Incentives Now (GAIN) Act, which was signed into law in the US on July 9, 2012.
The European Medicines Agency (EMA) has demonstrated that it is possible to develop a pathway for antibacterials that is reasonable. Late in 2011, the EMA released its new antibacterial guidance which was highly praised for prioritizing feasibility. This is highlighted by reports that some US pharmaceutical companies are now heading to Europe to negotiate clinical trial design, with the intention to first register in Europe before approaching the US regulator.
Can the FDA’s new antibacterial taskforce develop and issue guidance for antibacterial clinical trials that actually work? The FDA faces major hurdles and Datamonitor remains skeptical as to its success. Antibacterial drug development has taken some major hits over recent years, and as a result seen a mass exodus by some of the larger players. However, if the FDA is successful, we may finally see a much needed resurgence of and reinvestment in the antibacterial sector, and perhaps some of the promising antibacterials that have been lurking in the pipeline will finally see the light of day.
Posted in Infectious Diseases.