SOLIRIS® (Eculizumab) As a Treatment for Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).” Alexion Pharmaceuticals, Inc, 22 Feb

Page Indication Date Approved Date Updated 2 Neuromyelitis Optica (Devic’s Syndrome) June 27, 2019 June 28, 2019 3 Myasthenia Gravis Oct 23, 2017 May 24, 2019 4 Atypical Hemolytic Uremic Syndrome Sept 23, 2011 May 24, 2019 5 Paroxysmal Nocturnal Hemoglobinuria March 16, 2007 May 24, 2019

Drug Information Regulatory Information Manufacturer: Alexion Pharmaceuticals Application Type: Supplemental BLA Original Anticipated Approval Drug Brand 6/28/2019 Soliris (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 6/27/2019 eculizumab Name: Regulatory Status Reason: N/A Orphan Drug Designation: 6/24/2013 Drug Type: Monoclonal Antibody FDA Fast Track Designation: N/A Breakthrough Therapy Route of N/A Intravenous Designation Administration: Priority Review Designation: 2/22/2019 Indication Details Sales Forecast Indication Prevalence Prevalence Type Neuromyelitis U.S. 1-10 / 100,000 Optica (Devic’s Global 1-10 / 100,000 Syndrome)

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: May 23, 2019. Comments Section

On February 22, 2019, FDA accepted for review the supplemental BLA for Soliris (eculizumab) as a treatment for patients with neuromyelitis optica spectrum disorder (NMOSD) who have anti-aquaporin-4 (AQP4) auto antibodies. The FDA granted Priority Review and set a PDUFA date of June 28, 2019.

UPDATE: On June 27, 2019, FDA approved Soliris (eculizumab) for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. Soliris is the first FDA-approved treatment for neuromyelitis optica spectrum disorder.

Sources: “FDA Approves First Treatment for Neuromyelitis Optica Spectrum Disorder, a Rare Autoimmune Disease of the Central Nervous System.” U.S. Food & Drug Administration, 27 June 2019, www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-neuromyelitis-optica-spectrum-disorder-rare- autoimmune-disease-central. “FDA Grants Priority Review and Accepts SBLA of SOLIRIS® (Eculizumab) as a Treatment for Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).” Alexion Pharmaceuticals, Inc, 22 Feb. 2019, news.alexionpharma.com/press-release/product-news/fda-grants-priority-review-and-accepts-sbla-soliris-eculizumab- treatment-. Accessed: May 24, 2019. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: May 24, 2019. “Neuromyelitis Optica Spectrum Disorder.” NORD - National Organization for Rare Disorders, rarediseases.org/rare-diseases/neuromyelitis-optica/. Accessed: May 24, 2019. SOLIRIS (eculizumab) [Package Insert]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2019.

Drug Information Regulatory Information Manufacturer: Alexion Pharmaceuticals Application Type: Supplemental BLA Original Anticipated Approval Drug Brand 10/23/2017 Soliris (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 10/23/2017 eculizumab Name: Regulatory Status Reason: N/A Orphan Drug Designation: 6/12/2014 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 Indication Prevalence Prevalence Type Myasthenia U.S. 53,229 Gravis Global 441,748

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: May 23, 2019. Comments Section

On October 23, 2017, FDA approved Soliris (eculizumab) for the treatment of adult patients with generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody positive.

Myasthenia Gravis Prevalence: affects approximately 14-40 per 100,000 individuals in the U.S.** Myasthenia Gravis affects about 20 per 100,000 people worldwide.*

Sources: “Drugs@FDA: FDA Approved Drug Products - Soliris.” U.S. Food and Drug Administration, www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed: May 24, 2019. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: May 24, 2019. * “Myasthenia Gravis - Genetics Home Reference.” National Institutes of Health - U.S. National Library of Medicine, 14 May 2019, ghr.nlm.nih.gov/condition/myasthenia-gravis#statistics. Accessed: May 24, 2019. ** “Myasthenia Gravis - Rare Disease Database.” NORD - National Organization for Rare Disorders, rarediseases.org/rare-diseases/myasthenia-gravis/. Accessed: May 24, 2019. SOLIRIS (eculizumab) [Package Insert]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2018.

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

Drug Generic Regulatory Status Date: 9/23/2011 eculizumab Name: Regulatory Status Reason: N/A Orphan Drug Designation: 4/29/2009 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 Indication Prevalence Prevalence Type Atypical Hemolytic U.S. > 1,500 Uremic Syndrome (Nondiarrhea- Associated Global N/A Hemolytic Uremic Syndrome)

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: May 24, 2019. Comments Section

On September 23, 2011, FDA approved Soliris (eculizumab) for the treatment of patients with atypical Hemolytic Uremic Syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.

The annual incidence of aHUS is estimated to be 2 cases per million in the U.S.; the prevalence is estimated to be 3.3 per million among patients below the age of 18.** aHUS accounts for approximately 5-10% of all cases of hemolytic uremic syndrome.*

Sources: * “Atypical Hemolytic Uremic Syndrome - Rare Disease Database.” NORD - National Organization for Rare Disorders, rarediseases.org/rare-diseases/atypical- hemolytic-uremic-syndrome/. Accessed: May 24, 2019. “Drugs@FDA: FDA Approved Drug Products - Soliris.” U.S. Food and Drug Administration, www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed: May 24, 2019. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: May 24, 2019. “Just How Many AHUS Patients Are There?” AHUS Alliance, www.ahusallianceaction.org/just-many-ahus-patients/. Accessed: May 24, 2019. SOLIRIS (eculizumab) [Package Insert]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2018. ** Yoshida Y, Kato H, Nangaku M. Atypical hemolytic uremic syndrome. Renal Replacement Therapy (2017) 3:5. Available at: https://rrtjournal.biomedcentral.com/articles/10.1186/s41100-016-0088-1.

Drug Information Regulatory Information Manufacturer: Alexion Pharmaceuticals Application Type: BLA Original Anticipated Approval Drug Brand N/A Soliris (PDUFA): Name: Regulatory Status: Approved

Drug Generic Regulatory Status Date: 3/16/2007 eculizumab Name: Regulatory Status Reason: N/A Orphan Drug Designation: 8/20/2003 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 Indication Prevalence Prevalence Type Paroxysmal U.S. 6,524 Nocturnal Hemoglobinuria Global 103,186

Source: GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: May 24, 2019. Comments Section

On March 16, 2007, FDA approved Soliris (eculizumab) for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

The REMS for Soliris (eculizumab) was originally approved on June 4, 2010.

Paroxysmal Nocturnal Hemoglobinuria (PNH) Prevalence: estimated to affect between 1 and 5 per million people in the U.S.*

Sources: “Drugs@FDA: FDA Approved Drug Products - Soliris.” U.S. Food and Drug Administration, www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed: May 24, 2019. GlobalData, Pharma Intelligence Center. https://pharma.globaldata.com, Accessed: May 24, 2019. * “Paroxysmal Nocturnal Hemoglobinuria - Genetics Home Reference.” National Institutes of Health - U.S. National Library of Medicine, 14 May 2019, ghr.nlm.nih.gov/condition/paroxysmal-nocturnal-hemoglobinuria#statistics. Accessed: May 24, 2019. SOLIRIS (eculizumab) [Package Insert]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2018.