FDA Rejects Sandoz's Proposed Rituximab Biosimilar

Sandoz has announced that it has received a Complete Response Letter from the FDA for GP2013, its proposed rituximab biosimilar referencing Rituxan.

The company said in a statement that “Sandoz stands behind the robust body of evidence included in the regulatory submission and is currently evaluating the content of the letter. While disappointed, Sandoz remains committed to further discussions with FDA in order to bring this important medicine to US patients as soon as possible.”

Sandoz filed its Biologics License Application for GP2013 in the US in September 2017, following European approval of the drug, for marketing under the brand name Rixathon, in June 2017. The company had hoped to gain approval in all of the approved indications of the reference product: follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis, and microscopic polyangiitis.

In June 2017, Sandoz released primary results from the ASSIST-FL phase 3 trial of GP2013 in patients with advanced follicular lymphoma. The primary endpoint was comparability in overall response, with equivalence shown if the entire 95% confidence interval (CI) was within an equivalence margin of -12% to 12%. The primary endpoint was analyzed in patients who had received at least 1 (partial or complete) dose of the investigational treatment and who did not have any major protocol deviations. The primary endpoint was met: 271 of 311 patients (87%) receiving GP2013 and 274 of 313 patients (88%) receiving reference rituximab achieved an overall response. The 95% CI was within the predefined margin (range: -5.94 to 5.14).

Soon after, at the American College of Rheumatology's 2017 meeting in San Diego, California, researchers presented data that compared the safety and immunogenicity of switching from reference rituximab to GP2013 to continued treatment with reference rituximab in patients with active RA who had previously received reference rituximab prior to randomization into 2 treatment arms: 1 arm switched treatment to GP2013, and the control arm continued to receive reference rituximab.

The incidence of hypersensitivity was 9.4% in the switch group and 11.1% in the control group. Infusion-related reactions occurred in 11.3% and 18.5% of patients in each group, respectively, and the researchers concluded that the safety profile of patients who switched from the reference to the biosimilar was comparable with that of the patients who remained on the reference therapy.