FDA Approval Sought for Rituximab Biosimilar

David M. Reese, MD

A biologics license application has been submitted to the FDA for the rituximab (Rituxan) biosimilar ABP 798, according to the developers, Amgen and Allergan.¹

The application is based on analytical, pharmacokinetic, and clinical data, and also pharmacology and toxicology data from 2 clinical trials, results of which showed that there were no clinically meaningful differences between ABP 798 and reference rituximab.

"The US filing for ABP 798 marks an important milestone for Amgen, as it affirms our commitment to providing high-quality biosimilars that offer more life-altering biological treatment options and contribute to the sustainability of healthcare systems," David M. Reese, MD, executive vice president of Research and Development at Amgen, stated in a press release. "We look forward to working with the FDA to bring ABP 798 to market."

Topline results of the phase III JASMINE trial (NCT02747043), which directly compared ABP 798 with standard rituximab, were announced in August 2019.²

In the double-blind, comparative study, researchers evaluated the efficacy, safety, and immunogenicity of ABP 798 compared with rituximab in 256 adult patients with non-Hodgkin lymphoma. Patients received either ABP 798 or rituximab intravenously at 375 mg/m2 once weekly for 4 weeks, followed by dosing at weeks 12 and 20.

To be eligible for enrollment, patients must have been ≥18 years old; have histologically confirmed grade 1, 2, or 3a follicular B-cell CD20-expressing non-Hodgkin lymphoma within 12 months prior to randomization; have stage II, III, or IV measurable disease; and have low tumor burden based on Groupe d'Etudes des Lymphomes Folliculaires criteria.

Those with diffuse large cell component and/or grade 3b follicular non-Hodgkin lymphoma; have a history or presence of central nervous system metastases; have another malignancy beyond non-Hodgkin lymphoma within 5 years; be treated with systemic anti-infective therapies for a recent infection; underwent other investigational procedures that can impact study results; had prior chemotherapy, biological or immunological therapy; and received systemic corticosteroid use within 3 months prior to randomization were excluded from enrolling on the trial.

The primary endpoint was an assessment of objective response rate (ORR) at week 28. Secondary endpoints include risk difference of ORR at week 12, percent of patients with complete CD19 cell count depletion and total IgG and IgM antibody levels, treatment-emergent and serious adverse events, incidence of anti-drug antibodies, progression-free survival, overall survival, and geometric mean ratio of test to reference rituximab.

Results showed that the ORR at week 28 was within the prespecified margin for ABP 798 compared with rituximab. Additionally, safety and immunogenicity data with ABP 798 were similar to the reference product.

Earlier data showed that ABP 798 was similar to reference rituximab sourced from the European Union and the United States in relation to biological activity across a number of assays.³ Such tests evaluated the major and minor mechanisms of action across the approved rituximab indications. Data showed that the dose response profiles and relative activity for antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity were similar.

The JASMINE data are the second of two trials that are intended to support regulatory submissions for the rituximab biosimilar. A prior study, in which ABP 798 was evaluated in patients with moderate-to-severe rheumatoid arthritis, also met the primary endpoint of pharmacokinetic similarity.⁴

"We are excited about the progress that we've made to date through our partnership with Amgen, which includes the launch of the first two oncology therapeutic biosimilars in the US," David Nicholson, PhD, chief research and development officer at Allergan, stated in the press release. "With ABP 798, we look forward to the opportunity to continue to provide additional treatment options to patients suffering from serious illnesses."

Rituximab has indications alone or in combination with chemotherapy for patients with non-Hodgkin lymphoma, in combination with fludarabine and cyclophosphamide for chronic lymphocytic leukemia, and granulomatosis with polyangiitis and microscopic polyangiitis with glucocorticoids.

References

1. Amgen and Allergan submit biologics license application for ABP 798, biosimilar candidate to Rituxan (rituximab), to U.S. Food and Drug Administration [news release]. Amgen and Allergan. Published December 19, 2019. https://bit.ly/35HWEbH. Accessed December 19, 2019.
2. Amgen and Allergan announce positive top-line results from comparative clinical study of ABP 798, biosimilar candidate to Rituxan® (Rituximab) [news release]. Amgen. Published August 22, 2019. https://bit.ly/2L0pACF. Accessed August 22, 2019.
3. McBride H, Maher G, Sweet H, et al. Demonstration of functional similarity of proposed biosimilar ABP 798 to rituximab. Blood. 2017;130(suppl_1):5001. doi: 10.1182/blood.V130.Suppl_1.5001.5001.
4. Amgen and Allergan announce positive top-line results from phase 1/ phase 3 study of ABP 798, biosimilar candidate to rituximab. Amgen. Published January 24, 2019. https://bit.ly/2FVzjct. Accessed January 24, 2019.