AstraZeneca's Eculizumab Receives NMPA Approval in China for Neuromyelitis Optica Spectrum Disorder (NMOSD)

On October 17, AstraZeneca's complement C5 inhibitor Eculizumab received approval from the National Medical Products Administration for a new indication, to treat Neuromyelitis Optica Spectrum Disorder (NMOSD).

NMOSD is a rare and destructive disease that attacks the central nervous system (CNS), in which complement activation caused by anti-aquaporin-4 (AQP4) antibodies plays an important role in the disease process. The most common symptoms of NMOSD are transverse myelitis and optic neuritis; transverse myelitis can lead to mobility issues including paralysis, while optic neuritis can cause visual problems such as blindness. Patients with NMOSD experience unpredictable relapses, which may cause irreversible damage to the brain and spinal cord, leading to long-term disability.

Eculizumab (trade name: Soliris) is the world's first approved complement inhibitor, which inhibits the uncontrolled activation of the immune system by suppressing terminal complement. Eculizumab was first approved for marketing in China on August 23, 2018, for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), and on June 2, 2023, it was approved for the treatment of generalized myasthenia gravis (gMG).

Mechanism of Action of Eculizumab

A multinational, double-blind, parallel-controlled Phase III clinical trial codenamed PREVENT evaluated the efficacy and safety of Soliris in treating autoantibody-positive NMOSD with anti-AQP4 antibodies. The trial enrolled 143 adult patients who had at least two relapses within the past 12 months or three relapses within 24 months, including at least one relapse within 12 months prior to screening, and were randomly assigned to receive either Soliris or placebo in a 2:1 ratio.

Results showed that, compared with the placebo group, the risk of NMOSD relapse in the Soliris group was reduced by 94.2% (p<0.0001). At 48 weeks, 97.9% of patients treated with Soliris had no relapse, compared to 63.2% in the placebo group. On key secondary endpoints, Soliris treatment reduced the adjudicated annualized relapse rate by 95.5% compared with placebo (p<0.0001). Overall, Soliris was well tolerated, and its safety profile was consistent with previous clinical studies and its performance in other approved indications.

Eculizumab was initially developed by Alexion. On December 12, 2020, AstraZeneca acquired Alexion for $39 billion, gaining two key complement C5 inhibitors: Eculizumab and Ravulizumab (brand name: Ultomiris). According to AstraZeneca's financial report, in 2022, the global sales of Soliris and Ultomiris were $3.762 billion and $1.965 billion, respectively.

AstraZeneca has made a comprehensive layout in the complement field. In addition to Soliris and Ultomiris, danicopan, the company's first-in-class oral Factor D inhibitor, achieved significant success as an add-on therapy to C5 inhibitors in Phase III trials for the treatment of PNH (for details, see: ).

In addition, AstraZeneca's globally first-in-class C5/albumin bispecific antibody ALXN1720 has advanced to Phase II clinical trials. ALXN1720 is a third-generation C5 inhibitor, a mini-bispecific antibody (25kD), comprising only the heavy chain variable region (VH) of an antibody targeting C5 and an antibody fragment that specifically binds to albumin. Its smaller molecular weight offers better permeability, and its binding to albumin can extend its half-life. ALXN1720 is expected to become a once-weekly subcutaneous injection therapy that can be administered at home. ALXN1720 has completed a Phase II study for generalized myasthenia gravis (gMG), but the results have not been disclosed. AstraZeneca will initiate a Phase III study of ALXN1720 for the treatment of gMG this year.

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