Subcutaneous rituximab recommended for approval by FDA’s ODAC in Follicular Lymphoma, Diffuse Large B-Cell Lymphoma, and Chronic Lymphocytic Leukemia

A novel, subcutaneous (SC) co-formulation of rituximab and hyaluronidase (which aids delivery of medicine beneath the skin) has been unanimously (11 vs 0) recommended for approval by the U.S. Food and Drug Administration’s (FDA’s) Oncologic Drugs Advisory Committee (ODAC).

The indications proposed for Genentech’s SC rituximab treatment include: Newly Diagnosed (ND) DLBCL and FL, as well as Relapsed/Refractory (R/R) FL, low grade Lymphoma, and CLL.

ODAC’s recommendation is based on results of five clinical trials, including a total of 2,000 patients with a range of hematological malignancies:

• SparkThera (NCT00930514); phase Ib maintenance study in ND or R/R FL
• SABRINA (NCT01200758); phase III induction and maintenance study in ND FL
• SAWYER (NCT01292603); phase Ib study in ND CLL
• MabEase (NCT01649856); phase III study in ND DLBCL
• PrefMab (NCT01724021); phase III patient preference study in ND FL and DLBCL

Overall, the results show that the efficacy, safety, and pharmacokinetics of SC versus IV rituximab are non-inferior.

Key Highlights:

MabEase trial

• Evaluated SC (n = 381) versus IV (n = 195) rituximab combined with CHOP chemotherapy
• ORR = 71.8% in IV arm versus7% in SC arm
• CR = 42.1% in IV arm versus0% in SC arm
• HR for PFS = 1.23 (95% CI, 0.86–1.76; P = 0.280); HR for OS = 1.06 (95% CI, 0.68–1.65; P = 0.717)

SABRINA trial

• Evaluated SC (n = 205) versus IV (n = 205) rituximab combined with CHOP or CVP chemotherapy
• ORR = 84.9% in IV arm versus 4% in SC arm (P = 0.8911)
• CR = 32.2% in IV arm versus2% in SC arm
• HR for PFS = 0.84 (95% CI, 0.57–1.23; P = 0.3696); HR for OS = 0.81 (95% CI, 0.42–1.57; P = 0.5398).

SAWYER trial

• Compared SC (n = 88) versus IV (n = 88) rituximab in combination with chemotherapy
• ORR = 80.7% in IV arm versus 2% in SC arm (P = 0.4227)
• CR = 33% in IV arm versus1% in SC arm
• HR for PFS = 0.89 (95% CI, 0.49–1.64; P = 0.7192); HR for OS = 0.60 (95% CI, 0.24–1.52; P = 0.2789)

A final approval decision is expected from the FDA by June 26 2017. SC rituximab has been available in Europe as MabThera (SmPC) since 2014. The IV rituximab formulation currently holds FDA approval for ND FL, ND DLBCL, R/R low grade or FL, and ND and R/R CLL (PI).