| Drug Name |
EPYSQLI™(eculizumab-aagh) |
| Active Ingredient |
eculizumab |
| Date of Approval |
July 19, 2024 |
| Manufacturer |
Samsung Bioepis Co., Ltd. |
| Approval Pathways and Indications |
Approval Pathway: BLA
Indication:
• The treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
• The treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.
• Limitation of Use: EPYSQLI™ is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). |
| Therapeutic Class |
Complement C5 Inhibitor, Monoclonal Antibody |
| Formulation |
Injection for Intravenous Infusion : 300 mg/30 mL (10 mg/mL) in a single-dose vial |
| MoA |
Eculizumab-aagh, the active ingredient in EPYSQLI™, is a monoclonal antibody that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. Eculizumab products inhibit terminal complement-mediated intravascular hemolysis in PNH patients and complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. |
| Dosing and Administration |
Injection: 300 mg/30 mL (10 mg/mL) in a single-dose vial.
Recommended Dosage Regimen – PNH:
For patients 18 years of age and older, EPYSQLI™ therapy consists of:
• 600 mg weekly for the first 4 weeks, followed by
• 900 mg for the fifth dose 1 week later, then
• 900 mg every 2 weeks thereafter.
Administer EPYSQLI™ at the recommended dosage regimen time points, or within two days of these time points.
Recommended Dosage Regimen – aHUS:
For patients 18 years of age and older, EPYSQLI™ therapy consists of:
• 900 mg weekly for the first 4 weeks, followed by
• 1200 mg for the fifth dose 1 week later, then
• 1200 mg every 2 weeks thereafter.
For patients less than 18 years of age, administer EPYSQLI™ based upon body weight. |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
EPYSQLI™ is the second FDA-approved interchangeable biosimilar to SOLIRIS® following the approval of BKEMV™ in May 2024 for treating patients with PNH and aHUS, both considered rare diseases affecting 50,000 and 5,000 people in the United States respectively. According to the FDA, a rare disease affects fewer than 200,000 people in the United States.
EPYSQLI™ is available only through a restricted program—EPYSQLI™ Risk Evaluation and Mitigation Strategy. EPYSQLI™, BKEMV™, and SOLIRIS all carry a boxed warning about the increased risk of serious and life-threatening meningococcal infections caused by Neisseria meningitidis. Patients should complete meningococcal vaccination before starting any of the three medications and be monitored for early signs and symptoms of these infections.
Of note, approximately 70% of eculizumab-treated PNH patients are not dosed according to the label, and two-thirds of patients discontinue eculizumab within an average of 1.5 years, which may be attributed to several factors including the high treatment cost.
The interchangeability label will allow pharmacists to exchange EPYSQLI™ for Soliris without having to get permission from a physician prior, allowing patients to receive their medications in a more timely manner and avoid delays. |
| Expected Market Launch Date |
Data Unavailable |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
Data Unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
The clinical trials for EPYSQLI™ included PNH Study 1 (NCT00122330), a randomized, double-blind, placebo-controlled 26-week study assessing the safety and efficacy of EPYSQLI™ in PNH patients with hemolysis. Patients received 600 mg every 7±2 days for 4 weeks, followed by 900 mg after 7±2 days, and then 900 mg every 14±2 days. Patients were randomized to either eculizumab (n=43) or placebo (n=44), with major baseline characteristics balanced. EPYSQLI™ significantly reduced hemolysis (p<0.001), improved anemia, increased hemoglobin stabilization, and reduced the need for RBC transfusions. Fatigue and health-related quality of life improved after 3 weeks of treatment. PNH Study 2 (NCT00122304) was a single-arm 52-week study where 96 of 97 patients completed the study, showing sustained reduction in intravascular hemolysis and reduced need for RBC transfusions. A long-term extension study (E05-001, NCT00122317) with 187 EPYSQLI™-treated PNH patients demonstrated sustained reductions in hemolysis over 10 to 54 months. For aHUS, five single-arm studies evaluated EPYSQLI™'s efficacy using thrombotic microangiopathy (TMA) endpoints such as platelet count change, hematologic normalization, complete TMA response, TMA-event-free status, and daily TMA intervention rate. Studies C08-002A/B (NCT00844545 and NCT00844844) and C08-003A/B (NCT00838513 and NCT00844428) showed significant improvements in renal function, platelet counts, and reduction in dialysis needs over a median duration of 100 and 114 weeks, respectively. The retrospective study C09-001r (NCT01770951) in 19 pediatric patients showed consistent efficacy results with maintained platelet counts and no new dialysis requirements. Adult study C10-004 (NCT01194973) and pediatric/adolescent study C10-003 (NCT01193348) showed improvements in renal function, increased platelet counts, and reduced dialysis needs. In all aHUS studies, responses were consistent regardless of complement regulatory factor mutations. Overall, EPYSQLI™ demonstrated significant efficacy in reducing hemolysis and improving clinical outcomes in both PNH and aHUS patients. |
| Sources |
https://www.samsungbioepis.com/upload/attach/SB12_
Prescribing_Information.pdf
https://www.drugs.com/newdrugs/fda-approves-epysqli-eculizumab-aagh-biosimilar-soliris-6327.html
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