Rituximab and Filgrastim Biosimilars Being Reviewed by FDA

Today, Sandoz announced the acceptance by the Food and Drug Administration of its application for a biosimilar rituximab. This biosimilar was approved by the European Medicines Agency in June 2017.

The manufacturer included a phase 3 trial of the agent to treat follicular lymphoma, one of two Hodgkin’s lymphomas for which the originator product is approved to treat. Its pharmacokinetic and pharmacodynamics studies were conducted in patients with rheumatoid arthritis, another major indication.

fdaThis marks the second rituximab biosimilar to be submitted to the FDA; Celltrion’s application for its Truxima™ brand was submitted in June. Sandoz’s Zarxio® has been marketed since 2015, and Erelzi® (etanercept-szzs) was approved in August 2016 but is not yet marketed.

In addition, Adello Biologic announced that their 351(k) application for a new biosimilar filgrastim was sent to FDA on September 11. No FDA decision date was announced, but assuming a smooth ride through the process, a decision may be expected around the third quarter of 2018.

This is Adello’s first biosimilar brought to FDA application. According to its website, Adello is currently in clinical trials with a pegfilgrastim biosimilar, with preclinical development on a version of adalimumab.

Are 2 Biosimilars to the Same Originator Product Biosimilar to Each Other?

In Europe, several manufacturers are marketing approved biosimilars to the same originator product. In fact, 7 manufacturers compete for the biosimilar filgrastim market, 5 biosimilar versions of epoetin are sold, and 3 biosimilars of infliximab seek marketshare from Remicade®. In the US, this situation is not a reality yet. It will be one day, however, and it raises a couple of important questions.

We know that the biosimilars are not exactly the same structurally as the originator products, but how similar may they be to each other? In other words, at some point, payers will prefer one biosimilar version of filgrastim over another one, as some do currently with Zarxio® versus Neupogen®. We can assume that with 3 filgrastim biosimilars sold in the US, payers will seek to leverage 1 against the others and make it their preferred or only available form of filgrastim available. However, is another manufacturer’s version of filgrastim biosimilar to Zarxio? We can also assume that the new manufacturer’s product has received US Food and Drug Administration approval through testing for comparability only with the originator product—not against Zarxio. How about compared with Teva’s product tbo-filgrastim (a follow-on biologic, not a biosimilar according to the regulatory and statutory rules)?

What does this mean for switching products, much less interchangeability? Is one biosimilar interchangeable with another? Based on what we know about the FDA, the answer is likely no, as the agency seems to be having difficulty devising interchangeability guidelines for a biosimilar and its originator product.

Why is this important? Consider the patient with Crohn’s disease in 2019 who changes health plans. The patient was receiving biosimilar A, and the new plan covers only biosimilar B. Maybe he or she needs to enroll in a new plan in 2020, and the reverse is true. Regardless of whether we like it, that patient may be unintentionally providing real-world evidence of interchangeability.