Amgen and Allergan's Proposed Biosimilar Rituximab Shows Clinical Equivalence to Rituxan in NHL

Amgen and its partner Allergan have announced positive topline results of a study of a proposed biosimilar rituximab, ABP 798, in patients with non-Hodgkin lymphoma (NHL).

The JASMINE study, a randomized, double-blind comparative clinical trial, evaluated the efficacy, safety, and immunogenicity of the biosimilar compared with the reference rituximab, Rituxan, in 256 patients with CD20-positive B-cell NHL. Patients received either the biosimilar or its reference once weekly for 4 weeks, followed by dosing at weeks 12 and 20.

The study’s primary end point was risk difference of overall response rate (ORR) by week 28, and the partnership indicated in a statement that the risk difference of ORR fell within the prespecified margin, thereby demonstrating clinical equivalence of the biosimilar and its reference. Safety and immunogenicity were also comparable, said the companies.

In a statement, David M. Reese, MD, executive vice president of research and development at Amgen, said that "Today's results with ABP 798 demonstrate another positive development from Amgen's robust pipeline of biosimilar medicines and we look forward to working with regulatory agencies to bring this treatment to patients."

The study in patients with NHL is the second of a pair of studies intended to facilitate regulatory submissions for the biosimilar; in January 2019, the partnership announced positive topline results from a combined phase 1 and phase 3 study of the biosimilar in patients with rheumatoid arthritis (RA).

In the randomized, double-blind trial, 311 patients with RA received either the biosimilar, the US-sourced reference, or the EU-sourced reference rituximab. The study’s duration was 48 weeks, and it included a single transition for patients receiving the US-licensed reference to the biosimilar.

The study’s primary endpoint was pharmacokinetic (PK) similarity between the reference and the proposed biosimilar. The PK endpoints evaluated were the area under the serum concentration—time curve and maximum serum concentration, and Amgen and Allergan indicated that both fell within the prespecified equivalence margin. Safety and immunogenicity were comparable among all 3 treatment groups.

While it is not yet clear which indications Amgen and Allergan will seek for the biosimilar, if eventually approved in inflammatory disease indications, ABP 798 could provide an option for US patients with some inflammatory diseases who will not be served by already-approved biosimilars, Celltrion’s Truxima and Pfizer’s Ruxience.

When Truxima was approved by the FDA in late 2018, it was only granted indications in oncology. According to a representative from Celltrion, the “skinny label” was a response to challenges in the patent landscape.

When Ruxience was approved by the FDA in 2019, it carried both indications in oncology and granulomatosis with polyangiitis and microscopic polyangiitis, though not in other inflammatory indications, including RA. A Pfizer representative indicated that the company had entered into a global settlement with Genentech, which has exclusivity on certain indications for rituximab.