Drug name (Brand / Generic)
Soliris / Eculizumab
Company / Licensee
Paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS), generalised myasthaenia gravis (gMG), neuromyelitis optica spectrum disorder (NMOSD)
Approved in US, EU and Asia for PNH; approved in US for aHUS
Soliris (eculizumab) is a drug indicated for the treatment of paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS), generalised myasthaenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD).
The drug is developed and manufactured by US-based pharmaceutical company Alexion Pharmaceuticals, a subsidiary of AstraZeneca.
Soliris was given orphan drug designation by the US Food and Drug Administration (FDA) in October 2003. Alexion submitted a new drug application for Soliris to the FDA in September 2006.
The FDA first approved the drug in 2007 for the treatment of PNH in patients. Soliris also received FDA approval for the treatment of aHUS, gMG and NMOSD.
In February 2009, Soliris was approved by the Australian Therapeutic Goods Administration for the treatment of PNH.
The drug is also approved in the EU, Canada and Japan for the treatment of PNH, aHUS and gMG.
In August 2019, Soliris received marketing authorisation approval (MAA) from the European Commission (EC). Japan’s Ministry of Health, Labour and Welfare (MHLW) approved the drug for the prevention of relapse in patients with NMOSD in November 2019.
Soliris is used as an experimental emergency treatment for Covid-19 infection and severe pneumonia in a small number of patients. The potential role or efficacy of Soliris in Covid-19 treatment is still under investigation.
Causes of PNH, aHUS, gMG and NMOSD
PNH and aHUS are caused due to defects in protein (CD59) present on the surface of red blood cells (RBCs). This protein hinders complement protein from attacking the cells, thereby causing the destruction of RBCs.
PNH is the breakdown of the RBC at an early stage. It usually occurs in people with the missing PIG-A gene, which helps proteins to stick to the RBC. In the absence of PIG-A, the proteins cannot stick to the cells, which results in the RBC breaking down.
AHUS is a chronic illness in which a genetic deficiency may lead to uncontrolled activation of complement protein, causing small clots to form in blood vessels all over the body.
The uncontrolled complement activation may lead to reduced platelet count (thrombocytopaenia) and destruction of RBC. It may also cause damage to many vital organs, including the kidneys, brain and heart.
gMG is a chronic autoimmune neuromuscular disease, which begins with muscle weakness around eyeballs and eyelids and leads to weakness in the head, neck, limb and respiratory muscles. It occurs due to the generation of antibodies by the patient’s own body to attack the AChR receptor present on the muscle cells of the neuromuscular junction.
NMOSD is a rare, debilitating disorder in which the patient’s own body generates auto-antibodies against the AQP4 protein. The protein is present in the nerve cells of the eyes, brain and spinal cord for its growth and survival. The AQP4 auto-antibodies destroy the essential cells in the CNS and neurons.
Soliris mechanism of action
Eculizumab, the active ingredient of Soliris, is a recombinant monoclonal antibody that recognises and adheres to antigens present in the human body.
Eculizumab adheres to the C5 complement protein and blocks it. The C5 complement protein is a part of the immune system’s complement cascade whose activation causes the above conditions to develop.
Eculizumab adheres to the C5 complement protein and blocks it.
Clinical trials in PNH patients
TRIUMPH, a Phase III trial, began in November 2004 to evaluate and compare Soliris’ safety and efficacy against that of a placebo. It recruited 87 patients at 45 sites in the US, Canada, Europe and Australia.
Trial data released in September 2006 showed reductions in PNH symptoms. Haematologic normalisation was observed in 47% of Soliris-treated patients, compared with 0% of those given a placebo.
The Phase III SHEPHARD (safety in haemolytic PNH patients treated with eculizumab) trial enrolled 87 patients. It was initiated in August 2005 to evaluate Soliris’ safety and efficacy in PNH patients. The trial was completed by June 2007.
The Phase III AEGIS trial was conducted in 2008 to evaluate Soliris’ efficacy in 29 Japanese PNH patients. An 86% reduction in haemolysis was observed.
The AEGIS extension study was conducted for 26 weeks. A decrease in haemolysis was observed in Soliris-treated patients.
Clinical trials in aHUS patients
The FDA’s approval of Soliris for aHUS was based on three Phase II studies conducted to evaluate the drug’s safety and efficacy in aHUS patients undergoing plasma therapy, paediatric aHUS patients and plasma therapy-resistant patients respectively.
The first Phase II study enrolled 17 plasma therapy-resistant or sensitive patients. Haematologic normalisation was observed in 76% of the patients (13 out of 17). Around 87% of the patients (15 out of 17) treated with Soliris achieved thrombotic microangiopathy (TMA) free status.
The second trial was conducted in aHUS patients undergoing plasma therapy. It enrolled 20 patients, 80% of whom (16 out of 20) achieved TMA-free status. Haematologic normalisation was observed in 90% of the patients.
The third trial recruited 19 paediatric aHUS patients. Haematologic normalisation was reported in 89% of the patients.
The final trial data from all three trials were presented in June 2011 to the European Haematology Association.
Soliris (eculizumab) is a drug indicated for the treatment of paroxysmal nocturnal haemoglobinuria (PNH).
Clinical trials in gMG and NMOSD patients
The FDA’s approval of the drug for gMG was based on a Phase III, randomised, double-blind, placebo-controlled, multi-centre clinical study named REGAIN. The approval for NMOSD was based on the results of PREVENT, a Phase III, randomised, double-blind, placebo-controlled study.
In the REGAIN study, 125 patients were enrolled for 26 weeks. The trial’s primary endpoint was the change in the total score of the Myasthaenia Gravis-Specific Activities of Daily Living scale (MG-ADL). The total score was -4.2 in Soliris-treated patients compared with -2.3 in patients receiving a placebo. A lower score indicates a better clinical outcome.
A total of 143 patients were enrolled in the PREVENT trial, in which 96% of patients receiving Soliris were relapse-free compared with 45% patients on placebo at 144 weeks.