Eculizumab

The major therapeutic advance in AHUS has been the development of complement inhibitors, particularly drugs that block complement component C5.

Eculizumab and ravulizumab are monoclonal antibodies that inhibit C5 activation.

This prevents formation of the terminal complement complex and reduces complement-mediated endothelial injury.

For patients with a clear clinical suspicion of complement-mediated AHUS, current expert recommendations favor starting C5 inhibition as soon as possible, ideally within 24 hours of clinical suspicion when feasible.

Do not wait for the genetic panel to return before treating a patient with a convincing clinical presentation.

The same principle applies to waiting for every specialized complement assay.

Eculizumab is administered intravenously using an indication-specific induction and maintenance schedule.

Ravulizumab is a longer-acting C5 inhibitor that permits less frequent maintenance dosing.

I'd had my meningitis shots.

Ultomiris was becoming the standard treatment, but it hadn't quite been put in place, so I started on Soliris.

It's kind of amazing.

After my first loading dose of Soliris, all these wonky labs zipped into the normal zone.

It [laughs] it wa- it was, uh, the liver enzymes that were a little weird and all the, the list.

That's when the PNH journey started.

If you're gonna have a absurdly rare disease, it's nice to have one that has treatment.

And we have a, an abundance of treatments that, as I understand it, not everyone responds to different treatments, and I didn't.

Because they work quickly in most patients, they may be used as bridge therapies until other immunotherapies kick in, or in those who are refractory to standard treatments.

Eculizumab is one of the complement inhibitors, so that is also a true option.

Tell us a little bit more about the complement inhibitors.

They work by inhibiting the cleavage of C5 in the terminal complement cascade, which blocks complement-mediated destruction of the neuromuscular junction.

Eculizumab was the first of this class to be approved, and there are now two more drugs working by a similar mechanism that are available for the treatment.

One important note about this class of drugs, they increase the risk specifically of meningococcal infection, so patients should be vaccinated and warned about meningococcal disease.

And how about the FcRn inhibitors?