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Beyond safety data, phase 4 trials illustrate 'optimal' drug use, unmet market need
MAUI, Hawaii — Postmarketing, or phase 4, clinical trials can provide physicians and researchers with a broad range of information, from long-term safety findings to sales or marketing data, according to a presentation at the 2020 Rheumatology Winter Clinical Symposium.
“A key focus today will be to describe phase 4 studies, or what happens after a drug gets approved,” Mark C. Genovese, MD, James W. Raitt Professor of Medicine and clinical chief of the division of immunology and rheumatology at Stanford University, said. “Phase 4 studies are postmarketing studies, often done to delineate additional information. [They] might include evaluation of a drug, device or procedure’s risks — sometimes focusing on the benefits but often on the risk factor ratio — but might also be designed to assess optimal use.”
More specifically, phase 4 studies may include FDA risk evaluation and mitigation studies (REMS), which may be conducted if the FDA requires more information on the drug, to further understand real-world pharmacovigilance, understand sales or marketing goals, identify longer-term or changing adverse event profiles or for label expansion.
One way to accomplish many of these goals is with head-to-head trials, which have begun to proliferate in the rheumatology space, particularly in psoriasis. Genovese referenced the SPIRIT-H2H trial, which compared the IL-17 inhibitor ixekizumab (Taltz, Lilly) and the TNF inhibitor adalimumab (Humira, Abbvie) in 566 disease-modifying antirheumatic drug (DMARD)-naïve patients. “This is a phase 4 study that is not a post-regulatory commitment,” Genovese said. “It is really quite useful in helping us understand how a drug might perform in real life vs. a standard-of-care comparator.”
Genovese also referenced the EXCEED trial, in which McInnes and colleagues compared the IL-17 inhibitor secukinumab (Cosentyx, Novartis) with adalimumab in 853 patients. The analysis included 426 patients treated with secukinumab 300 mg and 427 treated with adalimumab 40 mg for 52 weeks.
Results showed that 67.4% of patients in the secukinumab arm reached the primary endpoint of ACR 20 response, compared with 61.5% for adalimumab. “This study provided very useful information — also in phase 4 — to understand how a drug might fit into our pattern, helping to understand how a drug might perform in terms of safety vs. a comparator, but also helping payers to understand how a drug might be positioned in a formulary in a world in which all drugs might cost the same,” Genovese said.
Ultimately, Genovese hoped that his presentation highlighted the process of drug development not only from the “epiphany” and inception phases, but illustrated how clinicians and researchers may continue the learning curve after the drug has been approved. He suggested that phase 4 studies “may be useful to a number of different stakeholders.” – by Rob Volansky
Reference:
Genovese M. FDA 201: What happens after approval? Why should Rheums care? Presented at RWCS Annual Meeting; Feb. 12-15, 2020; Maui, Hawaii.
Disclosure: Genovese reports Abbvie, Amgen, BeiGene, EMD, Galapagos, Genentech/Roche, Gilead, GSK, Lilly, Pfizer, Principia Bio, Regeneron, R-Pharm, Sandoz/Novartis, Sanofi, UCB and Unity Biotechnology.