SOLIRIS

What it is

SOLIRIS is supplied as 300 mg single-use glass vials containing 30 mL of 10 mg/mL sterile, preservative-free solution per vial. SOLIRIS (eculizumab rmc) is a concentrated solution for intravenous infusion that is sterile, clear, colourless, and preservative-free. SOLIRIS is a genetically-engineered humanised monoclonal antibody directed against the α-chain of the C5 complement protein. Eculizumab is a terminal complement inhibitor 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.

Approved indications

— Paroxysmal Nocturnal Haemoglobinuria (PNH) to reduce haemolysis. — Atypical Haemolytic Uraemic Syndrome (aHUS). — Adult patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody-positive.

Dosing overview

Dosing differs by indication. For PNH in adults, the initial phase is 600 mg administered via intravenous infusion every week for four weeks, followed by a maintenance phase of 900 mg on the fifth week and then 900 mg every 14 ± 2 days. For aHUS and NMOSD in adults, the initial phase is 900 mg administered via intravenous infusion every week for four weeks, followed by a maintenance phase of 1200 mg on the fifth week and then 1200 mg every 14 ± 2 days. Paediatric patients with PNH and aHUS weighing 40 kg or more receive adult dosing. Those weighing less than 40 kg receive weight-based dosing ranging from 300 mg to 900 mg depending on body weight. The safety and efficacy of SOLIRIS for the treatment of NMOSD in paediatric patients below the age of 18 years have not been established. In adults, the SOLIRIS admixture should be administered by intravenous infusion over 25 to 45 minutes.

Key safety warnings

SOLIRIS increases the risk of meningococcal infections. Life-threatening meningococcal infections and sepsis have occurred in patients treated with SOLIRIS, and meningococcal infection may become rapidly life-threatening or fatal if not recognised and treated early. Patients must be vaccinated against meningococcal infection at least 2 weeks prior to receiving SOLIRIS, unless the risk of delaying SOLIRIS therapy outweighs the risk of meningococcal infection. Vaccines against serogroups A, B, C, Y and W135 are recommended. Patients who initiate SOLIRIS treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients should be monitored for early signs of meningococcal infections, evaluated immediately if infection is suspected, and treated with antibiotics if necessary. SOLIRIS therapy should be administered with caution to patients with active systemic infections. SOLIRIS blocks terminal complement activation; therefore patients may have increased susceptibility to infections, especially with Neisseria and encapsulated bacteria. Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported. Severe thrombotic microangiopathy (TMA) complications were observed following SOLIRIS discontinuation in aHUS clinical studies (in some patients up to 127 weeks after discontinuation) and can occur at any time. If patients with PNH discontinue treatment with SOLIRIS, they should be closely monitored for signs and symptoms of serious intravascular haemolysis for at least 8 weeks to detect serious haemolysis and other reactions.

Contraindications

SOLIRIS is contraindicated in patients with hypersensitivity to eculizumab, murine proteins, or to any of the excipients. SOLIRIS should not be initiated in patients with unresolved Neisseria meningitidis infection, or in patients who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination.

PBS listing

SOLIRIS solution concentrate for intravenous infusion 300 mg in 30 mL is listed on the PBS with 12 items, under authority required restriction, with an ex-manufacturer price of A$5358.60.

Regulatory history

SOLIRIS eculizumab 300 mg/30 mL concentrated solution for intravenous infusion was first registered on the ARTG on 20 March 2009. In November 2014, the PBAC recommended listing of eculizumab for atypical haemolytic uraemic syndrome (aHUS) on the basis of high clinical effectiveness and acceptable cost-effectiveness. In July 2017, the PBAC recommended a change to the aHUS indication for prevention in patients at moderate-high risk of recurrence who have received a renal allograft for ESRD due to aHUS, limited to 3 months post-transplant. On 26 June 2020, the TGA approved SOLIRIS for the treatment of adult patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody-positive, based on an extension of indication.