FDA Review Finds Investigator Bias in Amgen T-Vec Vaccine Study

The latest clinical trial results for Amgen’s talimogene laherparepvec immunotherapy may not be as strong as the company hoped, say FDA advisory committee briefing documents.

FDA reviewers identified a number of problems with a large Phase III trial that compared the therapy, dubbed T-Vec, with an immune stimulating factor called GM-CSF. Chief among those concerns was that the amount and frequency of the doses patients were given were subject to investigator discretion and often inconsistent.

The FDA also cites 278 patients who dropped out of the study but were still included in six-month response data, raising the question of investigator bias in getting the positive results Amgen wanted to see for T-Vec.

Further, investigators included information only on patients they deemed to have complete or partial responses, potentially skewing the results, the agency says.

Reviewers also saw a possible red flag in the size of patients’ tumors. Some lesions were very small, raising questions about both the reliability of tumor measurement at the beginning of the trial and the accuracy of vaccine injections later, the briefing says.

Amgen claims T-Vec demonstrated a statistically significant improvement in partial and complete responses and that it fulfills an unmet need for melanoma therapies — even though the market for melanoma immunotherapies is growing with the recent approval of Merck’s Keytruda (pembrolizumab) and Bristol-Myers Squib’s Opdivo (nivolumab).

The Cellular, Tissue, and Gene Therapies Advisory Committee and Oncologic Drugs Advisory Committee will meet jointly Wednesday to discuss T-Vec’s safety and efficacy profiles, after which the FDA will make a final decision on the BLA.

Read the FDA’s briefing document at www.fdanews.com/04-27-15-Amgenbriefing.pdf. — Lena Freund