Predicting patent challenges for small-molecule drugs: A cross-sectional study.

Background: The high cost of prescription drugs in the United States is maintained by brand-name manufacturers' competition-free period made possible in part through patent protection, which generic competitors must challenge to enter the market early. Understanding the predictors of these challenges can inform policy development to encourage timely generic competition. Identifying categories of drugs systematically overlooked by challengers, such as those with low market size, highlights gaps where unchecked patent quality and high prices persist, and can help design policy interventions to help promote timely patient access to generic drugs including enhanced patent scrutiny or incentives for challenges. Our objective was to characterize and assess the extent to which market size and other drug characteristics can predict patent challenges for brand-name drugs.

Methods and findings: This cross-sectional study included new patented small-molecule drugs approved by the FDA from 2007 to 2018. Market size, patent, and patent challenge data came from IQVIA MIDAS pharmaceutical quarterly sales data, the FDA's Orange Book database, and the FDA's Paragraph IV list. Predictive models were constructed using random forest and elastic net classification. The primary outcome was the occurrence of a patent challenge within the first year of eligibility. Of the 210 new small-molecule drugs included in the sample, 55% experienced initiation of patent challenge within the first year of eligibility. Market value was the most important predictor variable, with larger markets being more likely to be associated with patent challenges. Drugs in the anti-infective therapeutic class or those with fast-track approval were less likely to be challenged. The limitations of this work arise from the exclusion of variables that were not readily available publicly, will be the target of future research, or were deemed beyond the scope of this project.

Conclusions: Generic competition does not occur with the same timeliness across all drug markets, which can leave granted patents of questionable merit in place and sustain high brand-name drug prices. Predictive models may help direct limited resources for post-grant patent validity review and adjust policy when generic competition is lacking.