Samsung Bioepis Co., Ltd. announced today that the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application (BLA) for EPYSQLI® (eculizumab-aagh) as a biosimilar to Soliris¹ (eculizumab). EPYSQLI has been approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. EPYSQLI is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). 

 

The FDA’s approval of EPYSQLI is based on a totality of evidence including analytical, non-clinical and clinical data demonstrating it is highly similar to Soliris, with no clinically meaningful differences between EPYSQLI and Soliris in terms of safety, purity and potency: The randomized Phase I, double-blind, three-arm, parallel group, single-dose study in healthy volunteers (NCT03722329) demonstrated pharmacokinetics (PK) equivalence and comparable pharmacodynamic (PD), safety, tolerability, and immunogenicity profiles between EPYSQLI and Soliris. The randomized Phase 3, double-blind, multicenter, cross-over study in PNH patients (NCT04058158) demonstrated clinical equivalence in efficacy, safety, PK, and immunogenicity between EPYSQLI and Soliris. 

 

“The FDA approval of EPYSQLI as a biosimilar to Soliris marks an important milestone for PNH and aHUS communities since biosimilars have a potential to positively impact patients and healthcare systems by reducing healthcare costs and improving access to treatments,” said Christopher Hansung Ko, President and Chief Executive Officer at Samsung Bioepis. “Our mission has been, and always will be improving the lives of patients by providing quality-assured, safe and effective biologic medicines, and our work to fulfill this mission is expanding into rare disease areas where patients continue to suffer from limited access to life-enhancing medicines,” he added.

 

The monoclonal antibody and anti-C5 complement inhibitor eculizumab is a well-established standard treatment for PNH and aHUS, rare diseases with an estimated US prevalence of approximately 50,000 and 5,000 respectively.^2,3  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.⁴ Biosimilars, biologic medicines that are highly similar to and have no clinically meaningful differences from an existing FDA-approved biologic, have the potential to relieve the financial burden of the healthcare system and improve access to biologic therapies.⁵  Biosimilar drugs must meet the same standards for pharmaceutical quality, safety and efficacy as reference products.⁵

 

Outside of the US, EPYSQLI has also been approved by the European Commission (EC) and Korea’s Ministry of Food and Drug Safety (MFDS) as a biosimilar to Soliris for the treatment of patients with PNH and aHUS. In countries where EPYSQLI is approved and available, EPYSQLI may not be prescribed and/or dispensed for other indications for which Soliris is approved. 

 

About EPYSQLI® (eculizumab-aagh) injection, for intravenous use

 

EPYSQLI is a complement inhibitor indicated for the treatment of patients with:

• paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis

• 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).

 

SELECTED SAFETY INFORMATION

 

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS   See full prescribing information for complete boxed warning.    Eculizumab products, complement inhibitors, increase the risk of serious infections caused by Neisseria meningitidis. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.   • Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of EPYSQLI, unless the risks of delaying therapy with EPYSQLI outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against meningococcal bacteria in patients receiving a complement inhibitor.    • Patients receiving eculizumab products are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected.   Because of the risk of serious meningococcal infections, EPYSQLI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called EPYSQLI REMS.

 

CONTRAINDICATIONS

 

EPYSQLI is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.

 

 

WARNINGS AND PRECAUTIONS

 

Serious Meningococcal Infections

 

Eculizumab products, complement inhibitors, increase a patient's susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (septicemia and/or meningitis) in any serogroup, including non-groupable strains. Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of EPYSQLI treatment is contraindicated in patients with unresolved serious Neisseria meningitidis infection. 

 

Complete or update meningococcal vaccination (for serogroups A, C, W, Y, and B) at least 2 weeks prior to administration of the first dose of EPYSQLI, according to current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations, considering the duration of therapy with EPYSQLI. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent EPYSQLI therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer meningococcal vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including eculizumab products. The benefits and risks of treatment with EPYSQLI, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by Neisseria meningitidis. 

 

Vaccination does not eliminate the risk of serious meningococcal infections, despite development of antibodies following vaccination.

 

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Meningococcal infection may become rapidly life- threatening or fatal if not recognized and treated early. Consider interruption of EPYSQLI in patients who are undergoing treatment for serious meningococcal infection, depending on the risks of interrupting treatment in the disease being treated.

 

EPYSQLI is available only through a restricted program under a REMS called EPYSQLI REMS, because of the risk of serious meningococcal infections. Further information is available at www.EPYSQLIREMS.com or 1-866-318-8144.

 

Other Infections

 

Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported.

 

Eculizumab products block terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections with Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with eculizumab products may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP recommendations. Patients receiving eculizumab products are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination. 

 

Monitoring Disease Manifestations after EPYSQLI Discontinuation

 

Treatment Discontinuation for PNH

Monitor patients after discontinuing EPYSQLI for at least 8 weeks to detect hemolysis.

 

Treatment Discontinuation for aHUS

After discontinuing EPYSQLI, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. In aHUS clinical trials, 18 patients (5 in the prospective studies) discontinued eculizumab treatment. TMA complications occurred following a missed dose in 5 patients, and eculizumab was reinitiated in 4 of these 5 patients.

 

Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis. In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of two, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during EPYSQLI treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during EPYSQLI treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during EPYSQLI treatment.

 

If TMA complications occur after EPYSQLI discontinuation, consider reinstitution of EPYSQLI treatment, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures.

 

Thrombosis Prevention and Management

The effect of withdrawal of anticoagulant therapy during eculizumab products treatment has not been established. Therefore, treatment with eculizumab products should not alter anticoagulant management.

 

Infusion-Related Reactions

Administration of eculizumab products may result in infusion-related reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion-related reaction which required discontinuation of eculizumab. Interrupt EPYSQLI infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

 

 

ADVERSE REACTIONS

The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) with the reference eculizumab are: headache, nasopharyngitis, back pain, and nausea.

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) with the reference eculizumab are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.