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PHILADELPHIA -- An investigational, self-injectable complement inhibitor rapidly improved symptoms for patients with generalized myasthenia gravis in a phase II trial, a researcher said here.

In a group of 44 patients, daily 0.3 mg/kg of significantly reduced Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Activities of Daily Living (MG-ADL), MG Composite, and 15-item Myasthenia Gravis Quality-of-Life revised scale (MGQoL15r) scores within 12 weeks, reported James Howard Jr., MD, of the University of North Carolina.

The therapy was relatively safe, with expected minor side effects of nausea and headache, and some bruising at the injection site, he said during the American Academy of Neurology meeting's prestigious .

Zilucoplan is a peptide agent that inhibits the C5 complement protein. The monoclonal antibody drug eculizumab (Soliris) has the same mechanism; it was in 2017 by the FDA, making it the first such agent approved for myasthenia gravis in modern times.

"I think you're going to see a move away from the commonly used immunosuppressive drugs we have because of side effect profiles," Howard told MedPage Today. "Adverse effects of therapies are often not considered when we treat patients because they're so happy they can do more, but now that we have these newer agents coming out, it's going to be a big player."

Generalized myasthenia gravis is an autoimmune disorder in which antibodies against acetylcholine receptors block signals transmitted from nerves to muscles. It causes muscle weakness that can affect the respiratory system and be debilitating.

Currently, treatment for generalized myasthenia gravis is limited, said Alejandro Tobon, MD, of the University of Texas Health Science Center in San Antonio, who was not involved with this study. Corticosteroids or pyridostigmine are commonly prescribed, but these therapies can have long-term adverse side effects and do not work for all patients, he added.

Eculizumab comes with a -- though zilucoplan may require a similar warning -- and it requires intravenous infusion.

"One of the good things about [zilucoplan] is it is administered subcutaneously by patients," Tobon told MedPage Today. "The eculizumab is an infusion that you have to get from an infusion center every two weeks, whereas this one you'll be able to maintain more independently, which is always convenient."

Zilucoplan differs structurally from eculizumab because in addition to targeting C5, it has a secondary action, Howard said.

"It targets the conversion of C5A to C6, so unlike the other complement inhibitor out there, which is only targeting C5, this one has a dual [mechanism]," Howard explained. He added, though, that most of the drug's effect is from C5 inhibition.

Howard noted as well that complement inhibitors, including both eculizumab and zilucoplan, are not effective for patients with so-called because this subclass of the disease is mediated by the IgG4 molecule.

Importantly, all patients receiving a complement inhibitor must be vaccinated against meningococcal disease because blocking C5 increases the risk for certain bacterial infections. In this study, all patients were pre-treated and no meningococcal infections occurred, Howard said.

For the , patients with mean baseline QMG scores ranging from 18.7 to 19.1 were randomized to receive placebo or zilucoplan at doses of 0.1 mg/kg or 0.3 mg/kg.

Changes in all four measures -- QMG, MG-ADL, MG Composite, and MGQoL15r -- remained significant at 24 weeks for the 0.3-mg/kg group, as well as in a subgroup of patients who crossed over from placebo to zilucoplan after 12 weeks. However, the lower dose was less pharmacokinetically effective, achieving about 88% complement inhibition, compared to 97% with the higher dose.

Disease duration in participants ranged from near zero to 20 years. Mean age was 48-55 in the three groups; most were white. Markedly fewer patients in the placebo group were male (27%) compared to the low- and high-dose zilucoplan arms (47% and 71%, respectively).

Notably, previous treatments did not appear to be associated with outcomes (P>0.20 for all), "indicating that the efficacy of zilucoplan is independent of prior therapies," they noted.

In terms of safety, 20% of patients in the placebo group required rescue therapy compared to 7% in the low-dose group and zero with the higher dose, the authors reported. Also, no serious adverse events occurred, though most patients in all groups reported adverse events of some kind.

Tobon emphasized that this was a small study and the rate of long-term infection should continue to be monitored to ensure patients receiving this type of drug are not at an increased risk.

"Therapeutics in myasthenia gravis have radically changed in the last 3 to 5 years and are going to continue to change in the forthcoming decade, with newer targeted therapies with very restricted side-effect profiles," Howard said.

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