Gefurulimab for myasthenia gravis

Last updated Sep. 23, 2024, by Joana Carvalho, PhD
Fact-checked by Inês Martins, PhD

What is gefurulimab for myasthenia gravis?

Gefurulimab, also known as ALXN1720, is an experimental therapy being developed by Alexion, Astrazeneca Rare Disease to ease disease symptoms in people with generalized myasthenia gravis (gMG).

It is designed to block the activation of the complement system, a part of the immune system thought to be involved in the autoimmune attacks seen in gMG.

Now in Phase 3 clinical testing, gefurulimab is given via subcutaneous, or under-the-skin, injections that can be self-administered by patients or caregivers following adequate training.

Therapy snapshot

How does gefurulimab work in myasthenia gravis?

Myasthenia gravis (MG) is an autoimmune disease driven by self-reactive antibodies that mistakenly attack proteins involved in nerve-muscle communication, resulting in the disease’s hallmark symptoms of muscle weakness and fatigue. In most cases, these autoantibodies target proteins called acetylcholine receptors (AChRs), which are found on the surface muscle cells and play a key role in muscle contraction.

When MG-causing antibodies bind to their target, they can trigger the activation of the complement cascade — a group of proteins that normally circulate in the bloodstream in an inactive state, but that can be activated by certain stimuli, such as an infection. This complement activation is believed to contribute to the damaging autoimmune response that drives MG.

One of the key steps in complement activation is the cleavage of a protein called C5 into two subunits, C5a and C5b, which go on to promote further inflammation. Similar to Soliris (eculizumab) and Ultomiris (ravulizumab-cwvz), two approved gMG therapies also developed by Alexion, gefurulimab is designed to bind to C5 and prevent it from being cleaved, thereby inhibiting complement activation.

However, gefurulimab is a bispecific antibody that simultaneously binds to another molecule called albumin — a highly stable protein in the blood that normally helps to transport hormones and other molecules through the bloodstream. This helps extend gefurulimab’s half-life — the time it takes for the levels of the therapy in the blood to drop to half — facilitating weekly dosing.

Additionally, compared with other antibody-based therapies, gefurulimab has a relatively low molecular weight that allows it to be concentrated in small volumes that are suitable for subcutaneous self-administration.

How will gefurulimab be administered in myasthenia gravis?

In a Phase 3 clinical trial involving people with gMG, gefurulimab is being administered in the form of subcutaneous injections, with patients receiving an initial loading dose followed by weekly maintenance doses, all adjusted based on weight. The therapy is being supplied in a single-use prefilled syringe and can be self-administered.

However, because gefurulimab is still in development for the treatment of gMG, it’s too soon to know if this will be the therapy’s dosing regimen when and if it is ultimately approved.

Gefurulimab in myasthenia gravis clinical trials

The safety, tolerability, and pharmacological properties of gefurulimab were first evaluated in a Phase 1 clinical trial (NCT04920370) in the U.K. that involved 97 healthy volunteers.

Participants, ages 18 to 45, were divided into 12 groups and randomly assigned to receive either gefurulimab or a placebo. Some groups received a single subcutaneous injection of the therapy (at doses ranging from 30 to 1,700 mg), while others were given multiple subcutaneous doses (100 or 300 mg) over the course of three weeks. There was also one group that received a single 300 mg into-the-vein infusion, and another that was given an initial loading subcutaneous dose of 900 mg followed by weekly 600 mg maintenance doses for seven weeks.

The study’s main goal was to assess the therapy’s safety and tolerability. Study data demonstrated that gefurulimab was well tolerated, with no serious side effects reported. All side effects observed over the course of the study were mild, and gefurulimab was found to have low immunogenicity, or a low chance of triggering an unwanted immune response that could reduce the treatment’s efficacy.

Additional findings also showed that the exposure and effects of gefurulimab were proportional to the dose administered. Complete complement inhibition was seen in participants receiving single doses equal to or greater than 100 mg, as well as in those treated with multiple doses at extended intervals.

Gefurulimab also had a high bioavailability (96%) when administered subcutaneously, meaning that 96% of the therapy was able to enter the body’s circulation and became available to reach its intended target.

Ongoing trials

A Phase 3 clinical trial called PREVAIL (NCT05556096) is underway to evaluate the safety and efficacy of gefurulimab in adults with gMG who are positive for self-reactive antibodies targeting AChR.

PREVAIL aims to enroll about 254 patients, who will be randomly assigned to receive either gefurulimab or a placebo, administered via subcutaneous injections using single-use prefilled syringes with a safety device. 

Treatment will be given as an initial weight-based loading dose, followed by weekly weight-based maintenance doses, for a total of 26 weeks (about six months). This will be followed by an open-label extension phase, where all patients will receive gefurulimab for up to 105 weeks, or around two years.

The trial’s main goal is to compare changes in MG Activities of Daily Living (MG-ADL) scores, a patient-reported measure of MG severity and impact on daily life activities, over the course of the 26-week randomized treatment period. Changes in other measures of MG severity, including the Quantitative MG and the MG Composite scales, will also be evaluated as secondary goals. Top-line data are planned for 2025 and the trial is expected to conclude in 2027.

Also underway is an open-label Phase 1 clinical trial (NCT06208488) in healthy volunteers that is comparing gefurulimab’s administration with a prefilled syringe carrying a needle safety device versus an autoinjector.

The study is expected to enroll approximately 175 healthy adults, who will be randomly assigned to receive a single 600 mg dose of gefurulimab with one of the administration methods in different parts of the body (abdomen, thigh, or upper arm). The goal is to determine if the safety, pharmacological properties, and immunogenicity of the treatment are comparable with both methods. The study is estimated to conclude in late 2024.

Common side effects of gefurulimab

Clinical trials of gefurulimab in people with gMG are ongoing and no results have been reported to date, so the therapy’s side effect profile in this patient population is still not known.

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