Me-Too Cancer Drugs Not Often Compared to Original

TOPLINE:

In an analysis of all FDA approvals for anticancer drugs from 2009 to 2020, only about 29% of next-in-class drugs were evaluated in head-to-head randomized clinical trials (RCTs) against their first-in-class counterparts. And in these head-to-head RCTs, only 22% of the “me-too” agents showed a survival benefit compared to the originals.

METHODOLOGY:

• Next-in-class, or “me-too,” oncology drugs may theoretically offer improved efficacy, safety, or broader indications, yet little is known about how often RCTs directly compare these me-too agents with first-in-class drugs, leaving their true therapeutic value uncertain.
• Researchers looked at all 332 FDA approvals for anticancer drugs between 2009 and 2020. After excluding supportive care treatments, biosimilars, and drugs with novel routes of administration, 94 RCTs for me-too agents that received FDA approvals were included.
• The researchers then identified which next-in-class drugs had RCTs comparing them with their first-in-class counterparts, both at and after approval.
• Among RCTs with head-to-head comparison, primary endpoints varied across trials, with 63% using progression-free survival, 11% using overall survival, and 11% using response rate as their primary endpoint; 77.8% of trials were designed as superiority trials.

TAKEAWAY:

• Only 27 RCTs that led to FDA approvals for me-too drugs — just under 29% — directly compared the new agent to the first-in-class drug (23 regular approvals and four accelerated approvals).
• Of these 27 RCTs, 12 trials were published at the time of FDA approval and 15 were published after approval. The median time to publication of post-approval trials was 2.8 years for regular approvals and 3.3 years for accelerated approvals.
• Overall, only six of the 27 trials (22.2%) demonstrated survival benefits, 14 trials (51.9%) met nonsurvival primary endpoints, and six trials (22.2%) failed to meet their primary endpoints. One trial is still ongoing.
• Among regular approvals designed as superiority trials, only 11 of 17 (64.7%) met their endpoints. Among accelerated approvals designed as superiority trials, three of four achieved their primary endpoints. The remaining six trials were not designed as superiority trials but met their primary endpoints.

IN PRACTICE:

“These results suggest a need for regulatory bodies to incentivize within-class RCTs,” the authors wrote, adding that “in cases where head-to-head RCTs were lacking, it is difficult to assess the true therapeutic value of next-in-class drugs.”

SOURCE:

This study, led by Timothée Olivier, MD, Geneva University Hospital, Geneva, Switzerland, was published online in JAMA Internal Medicine.

LIMITATIONS:

Drug development often occurred in parallel, limiting the feasibility of head-to-head comparisons. Some comparative trials published after the analysis period may not have been captured.

DISCLOSURES:

This project received funding from Arnold Ventures through a grant to the University of California San Francisco. One author reported receiving grants from Arnold Ventures and personal fees from John Hopkins University Press, MedPage, The Free Press, UnitedHealthcare, and other sources, outside the submitted work. Another author disclosed receiving honoraria from MashupMD and Medscape and research funding for his institution from Janssen, outside the submitted work. No other disclosures were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.