The FDA approval process can be long and expensive – one of many reasons drug companies have traditionally steered away from developing antibiotics, and instead, focused on more lucrative products.
A recent cost-benefit analysis exemplifies this issue: Carried out by the Office of Health Economics in London, the analysis calculated that the net present value (NPV) of a new antibiotic is only about $50 million, compared to approximately $1 billion for a drug used to treat a neuromuscular disease.
However, this lack of investment is coming to a head, as more life-threatening bacteria become resistant to current antibiotics.
“Antimicrobial resistance is a serious public health issue,” says Lyndsay Meyer, a FDA spokesperson. “The level of development and innovation for new antibacterial drugs has not kept pace with patient needs. At the same time, the persistent and sometimes indiscriminate use of existing antibacterial drugs worldwide has resulted in a decrease in the effectiveness of these drugs due to the development of resistance.”
In order to rectify these issues, the government has recently proposed legislation that would streamline the FDA’s approval process and provide incentives to drug companies to develop new antibiotics.
New options
The Limited-Population Antibacterial Drug (LPAD) pathway was originally approved by the House in July as part of the 21st Century Cures Act. Now, the Senate may include LPAD as part of its soon-to-be-released Innovations for Healthier Americans bill.
The approval pathway would help advance the development of new antibiotics, specifically for patients with serious and life-threatening bacterial infections resistant to current treatments.
“This targeted approach would make antibiotic development more feasible by allowing for smaller clinical development programs that are focused on the limited, high-risk populations that would use these new,” explains Elizabeth Jungman, director of public health programs at The Pew Charitable Trusts, a non-profit global research and public policy organization. “By making the development of high-need antibiotics more feasible, the LPAD pathway will help spur innovation and investment to reinvigorate the pipeline. Ultimately, it will bring new medicines to patients who have run out of options.”
The LPAD approval would also allow the FDA to assess these drugs by balancing the benefits they offer versus risks they present to the limited number of patients they are intended to treat.
While the FDA has not taken a position on the PATH Act, introduced in the U.S. Senate, it believes that the bill’s provision of a limited population antibacterial drug (LPAD) approval pathway is a promising idea.
“The proposed LPAD pathway would provide an important path to approval of these critical antibacterial drugs based on streamlined development programs,” says Meyer. “Such a pathway could assist in bringing treatments to seriously ill patients.”
The skeptics
The LPAD pathway approval is not being met without its skeptics. Those who were originally opposed to the 21st Century Cures Act criticized the deepening of the federal government’s involvement in medicine, and those combating the LPAD pathway do so for similar reasons. Others fear that the approval process will lead to lower standards.
But, Jungman assures us that the LPAD pathway would maintain the current standard for FDA approval. “As with drugs approved under FDA’s traditional pathway, sponsors seeking approval of antibiotics via the LPAD pathway must demonstrate safety and provide ‘substantial evidence’ of these drugs’ effectiveness,” she adds. (Substantial evidence’ is defined in Section 505(d) of the Federal Food, Drug, and Cosmetic Act as “evidence consisting of adequate and well-controlled investigations, including clinical investigations.”)
Mayer adds that the pathway would also need to include tools, such as a prominent branding mechanism and the FDA’s preapproval review of promotional materials, in order to convey to members of the healthcare community that the drug has been shown to be safe and effective for use only in a limited population.
Whether driven by necessity, or incentives, the pharmaceutical industry seems to be on board. Andrew Powaleny, a PhRMA spokesperson explains, “The development of innovative antibiotics to treat resistant infections is of great importance and the biopharmaceutical industry is committed to face the scientific and medical challenges to bring new and innovative antibiotics for America’s patients.”