Naproxcinod Review Sparks Debate over Role of Off-label Promotion in US Food and Drug Administration Decisions

摘要

The US Food and Drug Administration advisory panel review of NicOx's anti-inflammatory agent naproxcinod on 12 May sparked a debate between the agency and its outside experts over whether the potential effects of off-label promotion and literature on unapproved uses should be considered in drug approval decisions.The FDA's view that the panellists and the agency should take into account the potential for "subtle" off-label promotion of naproxcinod's potential blood pressure-moderating effects was rejected by some committee members, who believed it inappropriate to speculate on whether the company would engage in illegal marketing.Concerns about the potential for questionable promotional practices are often discussed at advisory committee meetings, particularly those involving opioid formulations purported to be abuse-resistant. However, the discourse between FDA staff and members of the agency's arthritis and drug safety/risk management advisory committees was striking given the forcefulness of FDA staff views and the resistance by some panellists to impute the past conduct of some pharmaceutical firms to a company that has never before marketed a product.Naproxcinod is a first-in-class cyclooxygenase-inhibiting nitric oxide donator. After oral ingestion, it is hydrolysed to naproxen and nitric oxide. Naproxcinod was developed with the intent of reducing the toxicities associated with nonsteroidal anti-inflammatory drugs, specifically blood pressure elevation and gastropathy. The nitric oxide component is thought to stimulate GI protective factors that are negatively affected by NSAIDS and to counteract the rise in blood pressure seen with the older drugs.The advisory panel overwhelmingly recommended against approval of naproxcinod for osteoarthritis. Panellists were not convinced that naproxcinod was non-inferior to naproxen, and they said longer-term safety data were needed, particularly since other NSAIDS used in the treatment of arthritis, such as the COX-2 inhibitors, were shown to have adverse CV outcomes only after long-term studies.