Reasons for Differences
Estimated phase transition probabilities and eventual approval success rates differed significantly by therapeutic class in Tufts’ study. For self-originated drugs, systemic anti-infective drugs enjoyed the greatest approval rate (23.9%), followed by musculoskeletal (20.4%), antineoplastic/immunologic (19.4%), respiratory (9.9%), GI/metabolism (9.4%), cardiovascular (8.7%), and CNS drugs lowest (8.2%).
“The distribution of disease categories does differ between large and small molecules. In particular, large molecule development is more concentrated in oncology and immunology, while small molecule development is more concentrated on cardiovascular and CNS conditions,” says Joseph A. DiMasi, Ph.D., director of economic analysis for Tufts CSDD. “However, differences in therapeutic class focus do not appear to explain the differences in success rates.”
What reasons, known or suspected, can explain that difference? “This is a difficult question to answer definitively, but it may be that large molecule development, in general, is more targeted, and, given their therapeutic focus and functions (e.g., immunologics and replacement therapies), safety issues may be less prevalent,” Dr. DiMasi speculates.
BIO’s Thomas also points out an interesting result of the BIO/BioMedTracker study: Oncology drugs had the lowest success rate at 5.6%, meaning just one in 20 cancer drugs advanced from Phase I all the way to approval. That rate combines the 11% success rate of lead cancer indications and 2% success rate of secondary indications.
Thomas shared a possible reason for the success-rate differences between diseases: With infectious disease, it’s easy to take a blood sample and quickly generate a readout that tells whether or not your drug is working. In oncology and cardiology, developing a drug is more difficult given the outcome studies required, with multiple efficacy endpoints, not to mention the complexity of the diseases; a cancer drug may work against several different enzymes, versus infectious disease, where a simpler drug targeting a single virus may suffice.