Rituximab Biosimilar Meets Endpoint in Phase III Follicular Lymphoma Trial

Pfizer has announced that PF-05280586, a biosimilar for rituximab (Rituxan/MabThera), has delivered positive top-line results, meeting its primary endpoint for overall response rate (ORR) in the in the phase III REFLECTIONS B3281006 trial for patients with follicular lymphoma.

The monoclonal antibody had equivalence in ORR compared with rituximab for the first-line treatment of patients with CD20-positive, low tumor burden FL, Pfizer, which is developing PF-05280586, reported yesterday.

“We are pleased to report on our fifth proposed biosimilar monoclonal antibody with positive study results. These results reinforce the potential of our proposed rituximab biosimilar in providing a safe and effective treatment option for patients,” Amrit Ray, MD, global president, Pfizer Essential Health Research and Development, said in a press release. “As a global leader in novel biologics, and with one of the broadest global portfolios in oncology, we are delivering on our commitment to advancing high-quality medicines for the millions of patients with cancer around the world today and in the future.”

PF-05280586 is an investigational compound and has not received regulatory approval in any country. It is indicated for the treatment of patients with certain types of CD20-positive non-Hodgkin lymphoma and CD20-positive chronic lymphocytic leukemia.

Rituximab has several approved indications, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.

In 2006, the FDA approved rituximab for use in combination with CVP (cyclophosphamide, vincristine, and prednisolone; R-CVP) for treatment-naïve patients with FL based on results from a randomized phase III trial.

In the 322-patient trial, 162 patients received R-CVP and 160 patients received CVP alone. All patients received up to eight 3-week cycles of CVP. Patients in the R-CVP arm received 375 mg/m²of rituximab on day 1 of each treatment cycle.¹

About one-quarter of the patient population was aged >60 years. Nearly all (99%) had stage III or IV disease and 50% had an IPI score ≥2. Progression-free survival (PFS) results based on investigator assessment were similar to those obtained by an independent review.

Investigators found that R-CVP improved median PFS compared with CVP alone (2.4 vs 1.4 years). This translated into a 56% (HR, 0.44;P= .0001) reduced risk for disease progression, relapse, or death compared with CVP alone.

Patients assigned to R-CVP were more likely to experience rash (17% vs 5%), cough (15% vs 6%), flushing (15% vs 3%), rigors (10% vs 2%), pruritus (10% vs 1%), neutropenia (8% vs 3%), and chest tightness (7% vs 1%).

Rituximab is also approved as a maintenance therapy in patients with FL who reached a complete or partial response following initial therapy with rituximab plus chemotherapy. In a pivotal trial, 1018 patients who achieved a response to rituximab plus chemotherapy were randomized 1:1 to maintenance rituximab (n = 505) or observation (n = 513).²The risk of disease progression or death was improved by 46% with maintenance rituximab versus observation.

PF-05280586 is one of several biosimilars in mid-to-late stage development at Pfizer, including 3 in oncology.

In September 2017, the FDA accepted a biologics license application for the rituximab biosimilar Rixathon (GP2013), which is manufactured by Sandoz (Novartis). Also in September 2017, the FDA approved ABP-215 (bevacizumab-awwb; Mvasi), a biosimilar for bevacizumab (Avastin), as the first FDA-approved biosimilar for the treatment of patients with cancer. In December 2017, the FDA approved the trastuzumab (Herceptin) biosimilar MYL-1401O (Ogivri; trastuzumab-dkst).

References:

1. FDA Approves Two New Indications for Rituxan in Patients With Non-Hodgkin's Lymphoma. Genentech. Published: September 29, 2006. Accessed: January 24, 2018. http://bit.ly/2Dwmykl.
2. Rituximab Full Prescribing Information. Accessed: January 24, 2018. http://bit.ly/2n7X5GZ.