More Data Underscore the Safety and Efficacy of CT-P10 in Hematological Conditions

Celltrion’s CT-P10, a biosimilar rituximab that was FDA approved under the brand name Truxima in November 2018, is already in wide use for a host of indications in many regulatory territories. During this week’s 60th Annual Meeting and Exposition of the American Society of Hematology in San Diego, California, multiple research teams are reporting data that underscore the safety and efficacy of CT-P10 in hematological conditions.

Low Tumor Burden Follicular Lymphoma

First, researchers reported on results from the first 7 months of an ongoing phase 3 study to demonstrate the similarity, in terms of efficacy and safety, of CT-P10 and reference rituximab as monotherapy in patients with newly diagnosed, previously untreated follicular lymphoma (FL) with low tumor burden.¹

In the study, 258 patients with stage 2 to 4, grade 1 to 3 FL were randomized to receive either the biosimilar (n = 130) or the reference (n = 128) as monotherapy for 4 weeks as induction, followed by maintenance therapy every 2 months for 2 years (overall, 231 patients completed 7 months). Patients with complete response, partial response, or stable disease after induction were eligible for maintenance.

At 7 months, an overall response rate (ORR) of 83.1% for CT-P10 and 81.3% for the reference rituximab was observed. The ORR difference was 1.8%, and 90% CI of the treatment difference estimate fell within the prespecified equivalence margin of ±17% (—6.43 to 10.20).

Similar safety profiles were observed for the 2 products; treatment-emergent adverse events were reported in 71% of the biosimilar group and 67% of the reference group. The proportion of patients who developed antidrug antibodies (ADAs) was similar between groups, with 0.8% of patients in the biosimilar group and 2.3% of patients in the reference group testing positive for ADAs in the 7-month period. One patient in the biosimilar group had neutralizing antibodies detected.

These data, say the researchers, demonstrate the therapeutic equivalence and comparable safety of the biosimilar and its reference at 7 months.

Immune Thrombotic Thrombocytopenic Purpura

In May 2017, the University College London Hospital in London, United Kingdom, switched from using the EU-licensed reference rituximab (MabThera) to the biosimilar. Researchers from the center reported on a retrospective cohort study of patients with immune thrombotic thrombocytopenic purpura—an acute, multisystem thrombotic microangiopathy mediated by immunoglobulin G antibodies that, if left untreated, has a mortality rate of over 90%—who were treated with either the reference or the biosimilar rituximab during the 2-year time period beginning in May 2016 and ending in May 2018.²

In total, 45 patients were treated with the reference rituximab, while 39 patients received the biosimilar.

According to the investigators, at 28 days after receiving rituximab, the mean platelet count was 263.3 (±10.69) in the reference group and 263.8 (±11.81) in the biosimilar group (90% CI, —24.95 to 27.91). These values remained similar at 3 months, with a mean platelet count of 275.8 (±10.05) in the reference group and 275.9 (±12.2) in the biosimilar group (90% CI, –25.96 to 26.2).

Levels of ADAMTS13—deficiencies of which lead to microthrombi through platelet aggregation—at 28 days was 50.87 IU/dL (±4.899) in the reference group and 50.88 IU/dL (±4.371) in the biosimilar group (90% CI, 11.01-11.03). These values rose to 85.4 IU/dL (±5.237) and 81.35 IU/dL (±4.549) in the 2 treatment groups, respectively, at month 3 (90% CI, 15.84-7.71).

Levels of CD19-positive cells dropped to 0.00259 (x 10⁹/L) (±0.00049) and 0.02151 (±001161) with Truxima (90% CI, 0.00073-0.037120), and were 0.01782 (±0.01033) and 0.02098 (±0.01042) respectively at 3 months (90% CI, —0.02139 to 0.02771).

Infusion reactions were comparable between the groups, with 33% of the reference group and 40% of the biosimilar group reporting infusion-related reactions. Furthermore, 15% of the reference group and 18% of the biosimilar group experienced infections.

The authors of the study reported that the reference and biosimilar demonstrated equivalence, and that the mean savings to the healthcare system per patient treated with the biosimilar was £4000 (approximately $5089).

References

1. Ogura M, Sancho JM, Cho SG, et al. Comparison of efficacy and safety of biosimilar CT-P10 to rituximab in patients with previously untreated low tumor burden follicular lymphoma (LTBFL): a randomized phase 3 study. Presented at the 60th Annual Meeting and Exposition of the American Society of Hematology; December 1-4, 2018; San Diego, California. Abstract 1596. ash.confex.com/ash/2018/webprogram/Paper110334.html

2. Stubbes MJ, Low R, McCuckian S, et al. Single centre UK comparison of biosimilar rituximab (Truxima) with the originator (MabThera) in patients with immune mediated thrombotic thrombocytopenia purpura. Presented at the 60th Annual Meeting and Exposition of the American Society of Hematology; December 1-4, 2018; San Diego, California. Abstract 3750. ash.confex.com/ash/2018/webprogram/Paper114765.html.