First to Launch, First to Falter? An Investigation Into the Clinical Benefits and HTA Outcomes for First-in-Class Drugs

OBJECTIVES: To meta-analyse and compare the clinical benefits and HTA outcomes for three product classes, namely first-in-class (FIC), advance-in-class (AIC) and addition-in-class drugs (AdIC), across all therapeutic areas.

METHODS: FDA drug approvals between 2014 and 2019 were screened to identify FIC and AIC drugs. A sample of AdIC drugs was identified from an existing LSE Health dataset on drug approvals and HTA. Corresponding HTA outcomes were identified across England, Scotland, Canada and Australia. Data was extracted on regulatory approval dates, HTA outcomes and dates, clinical study design, and QALY gains. The sample was restricted to drugs for which QALY estimates were submitted by the manufacturer. Descriptive statistics and logistic regressions were utilised to explore differences in the characteristics of first-in-class, advance in class and addition-in-class, and their impact on HTA outcomes and timelines.

RESULTS: 224 drug-indication pairs are included in the analysis. Preliminary results indicate that, on average, AIC (1.07, p<0.05) and AdIC (1.27, p<0.05) drugs provide significantly fewer QALYs relative to the existing standard of care than FIC (2.90) drugs. 22% of FIC drugs were rejected at HTA, compared to 12% of AIC and 18% of AdIC drugs. Time from MA to HTA was longest for AIC drugs (9.8 months), followed by FIC (9.4 months) and addition-in-class (8.1 months) drugs.

CONCLUSIONS: FIC drugs provide greater health benefits than AIC and AdIC drugs. In theory, the first to enter a market enjoys an advantage in terms of brand recognition and product loyalty. In practice, first-movers may face higher barriers to entry. Despite providing greater health gains, FIC drugs do not appear to benefit from faster time-to-HTA approval or better HTA outcomes. Our analysis is limited by the scarce availability of QALY estimates in HTA reports.