Differential Legal Protections for Biologics vs Small-Molecule Drugs in the US.

Abstract

Importance: Biologics approved by the US Food and Drug Administration (FDA) receive 12 years of guaranteed protection from biosimilar competition compared with 5 years of protection from generic competition for new small-molecule drugs. Under the 2022 Inflation Reduction Act, biologics are exempt from selection for Medicare price negotiation for 11 years compared with 7 years for small-molecule drugs. Congress codified these differing legal protections on the premise that biologics require more time and resources to develop and have weaker patent protection, necessitating additional protections for manufacturers to recoup their development costs and generate adequate returns on investment.

Objective: To review empirical evidence from the US experience with biologics to analyze the assumptions underlying longer periods of market exclusivity and protection from price negotiation compared with small-molecule drugs.

Evidence review: Recent data on development times, clinical trial success rates, research and development costs, patent protection, market exclusivity periods, revenues, and treatment costs of biologics vs small-molecule drugs were analyzed.

Findings: The FDA approved 599 new therapeutic agents from 2009-2023, of which 159 (27%) were biologics and 440 (73%) were small-molecule drugs. Median development times were 12.6 years (IQR, 10.6-15.3 years) for biologics vs 12.7 years (IQR, 10.2-15.5 years) for small-molecule drugs (P = .76). Biologics had higher clinical trial success rates at every phase of development. Median development costs were estimated to be $3.0 billion (IQR, $1.3 billion-$5.5 billion) for biologics and $2.1 billion (IQR, $1.3 billion-$3.7 billion) for small-molecule drugs (P = .39). Biologics were protected by a median of 14 patents (IQR, 5-24 patents) compared with 3 patents (IQR, 2-5 patents) for small-molecule drugs (P < .001). The median time to biosimilar competition was 20.3 years (IQR, 16.9-21.7 years) compared with 12.6 years (IQR, 12.5-13.5 years) for small-molecule drugs. Biologics achieved higher median peak revenues ($1.1 billion in year 13; IQR, $0.5 billion-$2.9 billion) than small-molecule drugs ($0.5 billion in year 8; IQR, $0.1 billion-$1.2 billion; P = .01) and had higher median revenues in each year following FDA approval. The median annual cost of treatment was $92 000 (IQR, $31 000-$357 000) for biologics and $33 000 (IQR, $4000-$177 000) for small-molecule drugs (P = .005).

Conclusions and relevance: There is little evidence to support biologics having longer periods of market exclusivity or protection from negotiation. As a result of differential treatment, US law appears to overly reward the development of biologics relative to small-molecule drugs.