FDA Rebukes Amgen for Misleading Neulasta Ads That May Hinder Biosimilar Uptake

On July 14, the U.S. FDA issued an Untitled Letter criticizing Amgen for its misleading advertising of Neulasta (pegfilgrastim), which may confuse physicians and hinder the use of corresponding low-cost biosimilars.

The FDA noted that the Neulasta banner ad cited a study claiming that the risk of febrile neutropenia (a life-threatening complication of cancer treatment) is statistically significantly higher when using a pre-filled syringe instead of Amgen's specialized on-body injector, Onpro. The theme of Amgen's series of animated advertisements is the Onpro injector, a specialized device applied to the skin (see figure below) that delivers the pegfilgrastim dose at a scheduled time. Users must wear the device for 27 hours before the dose begins. Subsequently, the scheduled dose is slowly released from the device over 45 minutes.

In an Untitled Letter dated July 7 sent to Amgen, the FDA noted that the study cited in the advertisement has "multiple limitations." For example, the study design did not ensure the appropriate identification of patients with febrile neutropenia, thereby precluding their inclusion in the analysis. Specifically, the study used an unvalidated algorithm to identify study participants.

The FDA also noted that the study design did not ensure that the patient populations using prefilled syringes and Onpro injectors were adequately balanced or that potential biases were controlled. "Selection bias is a critical issue in these studies, as even minor differences in the patient populations can significantly impact the incidence of febrile neutropenia and the conclusions drawn from the analysis."

The FDA warning states, "From a public health perspective, these violations are concerning. This misleading statement may lead healthcare providers (physicians) to conclude that Neulasta administered via the Onpro injector is more effective than Neulasta administered via a prefilled syringe, or more effective than biosimilars, since biosimilars can only be administered via prefilled syringes."

An Amgen spokesperson stated that the company "will work with the FDA to ensure we comply with FDA regulations regarding this matter."

As this warning was issued to Amgen, the U.S. biosimilar market is finally showing signs of delivering on its long-awaited promise to the public, following years of stagnation and a persistent failure to meet the cost savings anticipated by the healthcare system. Bernstein analyst Ronny Gal noted that total U.S. biosimilar sales exceeded $1 billion in the first quarter of this year, up from $555 million in the same period of 2020. In a report to investors earlier this month, he wrote that the U.S. market is now estimated at $4.1 billion overall, with Amgen and Pfizer dominating the sector, each generating approximately $1.4 billion to $1.5 billion in sales.

Amgen maintains a presence in both branded biologics and biosimilars. The company has a portfolio of biosimilars to compete with established biologics, but it also faces biosimilar competition for its own branded products, including Neulasta. In the first quarter of this year, Neulasta's sales in the United States were $421 million, down from $534 million a year earlier. Gal noted that since the introduction of biosimilars, the price of Neulasta has declined by 20%.

It is also worth noting that this letter to Amgen is the fourth such Untitled Letter issued by the FDA’s Office of Prescription Drug Promotion (OPDP) so far this year. In recent years, the OPDP routinely issued dozens of such letters annually to express concerns regarding drug advertising and promotional materials, but recently, the number of these letters has declined. Only six were issued last year, and ten in 2019.

However, according to Mark Senak, Senior Vice President and Partner at the public relations firm FleishmanHillard, large, well-established pharmaceutical companies have historically received very few such letters over the past decade. Since 2013, the FDA has issued only 10 letters to major pharmaceutical companies regarding advertising and promotional campaigns. “FDA enforcement is almost entirely directed at smaller, less experienced companies. I am not sure what went wrong at Amgen, but generally speaking, large companies have multiple layers of review processes, and everything is thoroughly vetted. Smaller companies may not have all the resources to review promotional and communication materials.”

Author: Shilin - Lanshan