Rituximab Biosimilar

Page Indication Date Approved Date Updated Ruxience (rituximab-pvvr) – Pfizer Microscopic Polyangiitis (MPA), 2 Granulomatosis with Polyangiitis (Wegener’s July 23, 2019 July 23, 2019 Granulomatosis) 3 Chronic Lymphocytic Leukemia (CLL) July 23, 2019 July 23, 2019 4 Follicular Lymphoma July 23, 2019 July 23, 2019 4 B-Cell Non-Hodgkin Lymphoma July 23, 2019 July 23, 2019 Truxima (rituximab-abbs) – Celltrion / Teva Pharmaceuticals 5 Chronic Lymphocytic Leukemia (CLL) May 23, 2019 July 9, 2019 6 Follicular Lymphoma Nov 28, 2018 July 9, 2019 May 23, 2019, 6 B-Cell Non-Hodgkin Lymphoma July 9, 2019 Nov 28, 2018 Rituxan (rituximab) – Genentech 7 Pemphigus Vulgaris June 7, 2018 July 9, 2019 Microscopic Polyangiitis (MPA), 8 Granulomatosis with Polyangiitis (Wegener’s April 19, 2011 July 9, 2019 Granulomatosis) 9 Chronic Lymphocytic Leukemia (CLL) Feb 18, 2010 July 9, 2019 10 Rheumatoid Arthritis Feb 28, 2006 July 9, 2019 Oct 19, 2012, Jan 28, 2011, 11 Follicular Lymphoma July 9, 2019 Sep 29, 2006, Nov 26, 1997 Oct 19, 2012, Jan 28, 2011, 11 B-Cell Non-Hodgkin Lymphoma July 9, 2019 Sep 29, 2006, Nov 26, 1997

Drug Information Regulatory Information Manufacturer: Pfizer Application Type: BLA Original Anticipated Approval Drug Brand 7/1/2019 Ruxience (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 7/23/2019 rituximab-pvvr Name: Regulatory Status Reason: N/A Orphan Drug Designation: N/A Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: N/A Indication Details Sales Forecast Prevalence Prevalence Indication Type Microscopic U.S. 3,516 Polyangiitis (MPA) Global 25,865 Prevalence Prevalence Indication Type Granulomatosis U.S. 24,611 with Polyangiitis (Wegener’s Global 55,563 Granulomatosis)

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 7, 2019. Comments Section

On July 23, 2019, FDA approved Ruxience (rituximab-pvvr), a biosimilar to Rituxan, for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) in adult patients in combination with glucocorticoids.

Sources: “Drugs@FDA: FDA Approved Drug Products - Ruxience.” U.S. Food & Drug Administration, www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761103. Accessed: July 23, 2019. “FDA Approves Pfizer's Biosimilar, RUXIENCE™ (Rituximab-Pvvr), for Certain Cancers and Autoimmune Conditions.” Pfizer Inc., 23 July 2019, investors.pfizer.com/investor-news/press-release-details/2019/FDA-Approves-Pfizers-Biosimilar-RUXIENCE-rituximab-pvvr-for-Certain-Cancers-and-Autoimmune- Conditions/default.aspx. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. RUXIENCE (rituximab-pvvr) [Package Insert]. NY, NY: Pfizer Inc.; 2019.

Drug Information Regulatory Information Manufacturer: Pfizer Application Type: BLA Original Anticipated Approval Drug Brand 7/1/2019 Ruxience (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 7/23/2019 rituximab-pvvr Name: Regulatory Status Reason: N/A Orphan Drug Designation: N/A Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: N/A Indication Details Sales Forecast Prevalence Prevalence Indication Type Chronic U.S. 222,762 Lymphocytic Leukemia (CLL) Global 713,429

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 7, 2019. Comments Section

On July 23, 2019, FDA approved Ruxience (rituximab-pvvr), a biosimilar to Rituxan, for the treatment of adult patients with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide (FC).

Drug Information Regulatory Information Manufacturer: Pfizer Application Type: BLA Original Anticipated Approval Drug Brand 7/1/2019 Ruxience (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 7/23/2019 rituximab-pvvr Name: Regulatory Status Reason: N/A Orphan Drug Designation: N/A Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: N/A Indication Details Sales Forecast Prevalence Prevalence Indication Type B-Cell Non- U.S. 512,386 Hodgkin Lymphoma Global 1,648,526 Prevalence Prevalence Indication Type Follicular U.S. 122,682 Lymphoma Global 394,710

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 7, 2019. Comments Section

On July 23, 2019, FDA approved Ruxience (rituximab-pvvr), a biosimilar to Rituxan, for the treatment of adult patients with: • Non-Hodgkin’s lymphoma (NHL) o Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent. o Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. o Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy. o Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other anthracycline-based chemotherapy regimens.

Drug Information Regulatory Information Manufacturer: Celltrion / Teva Pharmaceuticals Application Type: Supplemental BLA Original Anticipated Approval Drug Brand N/A Truxima (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 5/23/2019 rituximab-abbs Name: Regulatory Status Reason: N/A Orphan Drug Designation: N/A Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: N/A Indication Details Sales Forecast Prevalence Prevalence Indication Type Chronic U.S. 222,762 Lymphocytic Leukemia (CLL) Global 713,429

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 7, 2019. Comments Section

On May 23, 2019, FDA approved a new indication for Truxima (rituximab-abbs), a biosimilar to Rituxan, for the treatment of adult patients with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide (FC).

Sources: “Drugs@FDA: FDA Approved Drug Products - Truxima.” U.S. Food & Drug Administration, www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761088. Accessed: July 8, 2019. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. TRUXIMA (rituximab-abbs) [Package Insert]. Yeonsu-gu, Incheon, Republic of Korea: Celltrion, Inc.; 2019.

Drug Information Regulatory Information Manufacturer: Celltrion / Teva Pharmaceuticals Application Type: BLA, Supplemental BLA Original Anticipated Approval Drug Brand N/A Truxima (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 11/28/2018, 5/23/2019 rituximab-abbs Name: Regulatory Status Reason: N/A Orphan Drug Designation: N/A Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: N/A Indication Details Sales Forecast Prevalence Prevalence Indication Type B-Cell Non- U.S. 512,386 Hodgkin Lymphoma Global 1,648,526 Prevalence Prevalence Indication Type Follicular U.S. 122,682 Lymphoma Global 394,710

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 7, 2019. Comments Section

On November 28, 2018, FDA approved Truxima (rituximab-abbs), a biosimilar to Rituxan, for the treatment of adult patients with: • Non-Hodgkin’s lymphoma (NHL) o Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent. o Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. o Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.

On May 23, 2019, FDA approved a new indication for Truxima (rituximab-abbs) for the treatment of adult patients with previously untreated diffuse large B-cell, CD20-positive non-Hodgkin’s lymphoma (NHL) in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other anthracycline-based chemotherapy regimens.

Sources: “Celltrion and Teva Announce FDA Approval of TRUXIMA® (Rituximab-Abbs), a Biosimilar to RITUXAN®, for Three Non-Hodgkin’s Lymphoma Indications.” Celltrion, 29 Nov. 2018, www.celltrion.com/en/pr/reportDetail.do?seq=530. “Drugs@FDA: FDA Approved Drug Products - Truxima.” U.S. Food & Drug Administration, www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761088. Accessed: July 8, 2019. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. TRUXIMA (rituximab-abbs) [Package Insert]. Yeonsu-gu, Incheon, Republic of Korea: Celltrion, Inc.; 2019.

Drug Information Regulatory Information Manufacturer: Genentech Application Type: Supplemental BLA Original Anticipated Approval Drug Brand 7/13/2018 Rituxan (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 6/7/2018 rituximab Name: Regulatory Status Reason: N/A Orphan Drug Designation: 2/23/2015 Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of 3/24/2017 Intravenous Designation Administration: Priority Review Designation: 2/14/2018 Indication Details Sales Forecast Prevalence Prevalence Indication Type U.S. N/A Pemphigus 0.7-5 / Vulgaris Global 1,000,000 / yr**

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. Comments Section

On June 7, 2018, FDA approved Rituxan (rituximab) for the treatment of adult patients with moderate to severe pemphigus vulgaris (PV).

Pemphigus vulgaris (PV) accounts for up to 80% of all pemphigus cases.* Estimated incidence of pemphigus: 1-10 new cases per 1 million people worldwide.* Estimated prevalence of pemphigus: 30,000-40,000 cases in the United States.*

Sources: “Drugs@FDA: FDA Approved Drug Products - Rituxan.” U.S. Food & Drug Administration, www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103705. Accessed: July 8, 2019. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. * “Pemphigus.” International Pemphigus & Pemphigoid Foundation (IPPF), www.pemphigus.org/research/clinically-speaking/pemphigus/. Accessed: July 9, 2019. ** “Pemphigus.” NORD - National Organization for Rare Disorders, rarediseases.org/rare-diseases/pemphigus/. Accessed: July 9, 2019. RITUXAN (rituximab) [Package Insert]. South San Francisco, CA: Biogen and Genentech, Inc.; 2019.

Drug Information Regulatory Information Manufacturer: Genentech Application Type: Supplemental BLA Original Anticipated Approval Drug Brand 12/11/2019 Rituxan (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 4/19/2011 rituximab Name: Regulatory Status Reason: N/A Orphan Drug Designation: 2/14/2006 Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: 6/11/2019 Indication Details Sales Forecast Prevalence Prevalence Indication Type Microscopic U.S. 3,516 Polyangiitis (MPA) Global 25,865 Prevalence Prevalence Indication Type Granulomatosis U.S. 24,611 with Polyangiitis (Wegener’s Global 55,563 Granulomatosis)

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. Comments Section

On April 19, 2011, FDA approved Rituxan (rituximab) in combination with glucocorticoids for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA).

On June 12, 2019, FDA accepted the supplemental BLA and granted Priority Review for the use of MabThera/Rituxan (rituximab), in combination with glucocorticoids (GCC), for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children two years of age and older. A PDUFA date has been set for December 11, 2019.

Sources: “Drugs@FDA: FDA Approved Drug Products - Rituxan.” U.S. Food & Drug Administration, www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103705. Accessed: July 8, 2019. “FDA Grants Priority Review to Roche's Mabthera/Rituxan (Rituximab) in Children with Two Rare Blood Vessel Disorders.” Roche, 12 June 2019, www.roche.com/investors/updates/inv-update-2019-06-12.htm. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. RITUXAN (rituximab) [Package Insert]. South San Francisco, CA: Biogen and Genentech, Inc.; 2019.

Drug Information Regulatory Information Manufacturer: Genentech Application Type: Supplemental BLA Original Anticipated Approval Drug Brand N/A Rituxan (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 2/18/2010 rituximab Name: Regulatory Status Reason: N/A Orphan Drug Designation: 1/29/2004 Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: N/A Indication Details Sales Forecast Prevalence Prevalence Indication Type Chronic U.S. 222,762 Lymphocytic Leukemia (CLL) Global 713,429

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. Comments Section

On February 18, 2010, FDA approved Rituxan (rituximab) for the treatment of patients previously untreated and previously treated for CD20-positive chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide (FC).

Drug Information Regulatory Information Manufacturer: Genentech Application Type: Supplemental BLA Original Anticipated Approval Drug Brand N/A Rituxan (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 2/28/2006 rituximab Name: Regulatory Status Reason: N/A Orphan Drug Designation: N/A Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: N/A Indication Details Sales Forecast Prevalence Prevalence Indication Type Rheumatoid U.S. 2,377,410 Arthritis Global 21,639,599

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. Comments Section

On February 28, 2006, FDA approved Rituxan (rituximab) for the treatment of Rheumatoid Arthritis (RA) in combination with methotrexate in adult patients with moderately-to severely-active RA who have inadequate response to one or more TNF antagonist therapies.

Drug Information Regulatory Information Manufacturer: Genentech Application Type: BLA, Supplemental BLA Original Anticipated Approval Drug Brand N/A Rituxan (PDUFA): Name: Regulatory Status: Approved 11/26/1997, 9/29/2006, 1/28/2011, Drug Generic Regulatory Status Date: rituximab 10/19/2012 Name: Regulatory Status Reason: See Comments Section below Orphan Drug Designation: 6/13/1994 Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: N/A Indication Details Sales Forecast Prevalence Prevalence Indication Type B-Cell Non- U.S. 512,386 Hodgkin Lymphoma Global 1,648,526 Prevalence Prevalence Indication Type Follicular U.S. 122,682 Lymphoma Global 394,710

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: July 8, 2019. Comments Section

FDA approved Rituxan (rituximab) for the treatment of adult patients with: • November 26, 1997 – Relapsed or refractory, low-grade or follicular, CD20-positive B-cell non-Hodgkin’s lymphoma (NHL) as a single agent. • September 29, 2006 – Non-progressing (including stable disease), low-grade, CD20positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy. • January 28, 2011 – Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy. • October 19, 2012 – Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other anthracycline-based chemotherapy regimens.