On July 7, the FDA issued a warning letter to Amgen regarding an advertisement it ran promoting Neulasta® OnPro®, its on-body injector version of Neulasta (pegfilgrastim). In the animated advertisement, “the banner makes false or misleading claims and representations about the benefit of Neulasta,” states the letter. “These violations are concerning from a public health perspective, because this promotional communication’s misleading claims could cause healthcare providers to conclude that Neulasta delivered via the Onpro on-body injector (OBI) is more effective than Neulasta delivered via prefilled syringe (PFS) or that it is more effective than FDA-licensed biosimilar pegfilgrastim products, which are delivered via PFS.”
At issue is a study cited by Amgen in the banner ad, claiming that:
- “In a real-world study with nearly 11,000 patients, pegfilgrastim PFS resulted in a significantly higher risk of [febrile neutropenia or FN] vs. Onpro
- “Across all cycles of chemotherapy, the incidence of FN associated with [PFS] was 1.7% (n = 455) vs 1.3% (n = 126) for Neulasta Onpro
- “A large presentation of an upward arrow containing the claim, ‘31%* *P = .01’
The FDA took issue with Amgen’s misleading claim that this extremely small absolute percentage difference represented a significant difference. This is certainly not clinically significant, stated the FDA, despite its apparent statistical significance. Furthermore, the numeric difference may have resulted from at least two factors: “The study was not designed to ensure that patients with FN were appropriately identified for inclusion in the analysis.” Furthermore, the agency argued that “the study was not designed to ensure that the PFS and OBI patient populations were adequately balanced or controlled for potential bias.” Therefore, the FDA stated that the statistical significance of the finding may not be accurate.
Finally, the letter points out that Amgen suspiciously used the term “pegfilgrastim PFS” in describing the PFS arm of the study, rather than Neulasta PFS, which was actually used. This infers that biosimilar pegfilgrastims may have been included in the PFS arm, which was apparently not the case. “Healthcare providers could conclude that a biosimilar pegfilgrastim product delivered via PFS is not as effective as Amgen’s OBI product.”
The FDA warning letter concluded that the advertisement “misbrands Neulasta within the meaning of the FD&C Act,” and mandates a response within 15 days and action to cease violations of the Act.
One of the strategies used by Amgen to ward off erosion of its pegfilgrastim market has been to convert much of its original Neulasta PFS business to OnPro. That has been largely successful: According to March 2021 figures from Bernstein Research, OnPro has held onto approximately 55% of the marketshare in the face of four biosimilar PFS competitors. Neulasta PFS still held 15% marketshare, but this has declined steadily since the introduction of the biosimilars.
You might expect biopharmaceutical companies to know better, especially if they produce both biosimilars and reference products. Amgen ran afoul of the FDA’s push to restrict misinformation about biosimilars, and in doing so, also threw one of their own reference products under the bus.