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WASHINGTON -- A drug in advanced development for myasthenia gravis also showed promise as a treatment for primary Sjögren's syndrome, a researcher reported here.

Patients receiving the infusion drug, called nipocalimab, at 15 mg/kg every 2 weeks showed significantly greater improvement in a modified version of the after 24 weeks than was seen in a placebo group, according to Ghaith Noaiseh, MD, of the University of Kansas Medical Center in Kansas City.

Other efficacy measures also favored this dose of nipocalimab in the phase II trial, enough that a longer phase III study is planned, Noaiseh told attendees at the American College of Rheumatology's annual meeting.

Dosing at 5 mg/kg appeared less effective, however, with changes in "clinical" ESSDAI scores and other outcomes not differing much from the placebo group. But no safety concerns for the drug emerged in the 163-patient trial.

Sjögren's syndrome is marked and to a large extent driven by excess immunoglobulin G (IgG) release as well as anti-IgG autoantibodies, with manifestations in multiple organ systems. Nipocalimab represents a novel approach to interrupting this process. It's a monoclonal antibody that binds to so-called FcRn (a neonatal receptor protein that recognizes the Fc portion of immunoglobulins). In so doing, it prevents recycling of IgG antibodies back into circulation, thus diminishing their titers and also titers of anti-IgG antibodies. (Myasthenia gravis is another disease featuring excessive IgG activity; results from a phase III trial in this condition were reported last month.)

In the new Sjögren's trial, Noaiseh and colleagues randomized patients in equal numbers to high- or low-dose nipocalimab or placebo, with infusions given every 2 weeks during the 24-week treatment phase. Patients also returned at week 30 for a final evaluation.

The primary outcome measure was clinical ESSDAI: the regular, 12-domain questionnaire modified to remove the item about IgG levels. This had the effect of making it more stringent, Noaiseh explained, since nipocalimab would be expected to lower IgG levels even if it had no impact on symptoms or organ system involvement.

Indeed, the drug did have a profound effect on IgG. With the 15-mg/kg dose, average titers dropped 50% by week 2 and by another 10 percentage points at week 8. There IgG levels remained, but they rebounded nearly to baseline at week 30.

Mean changes from baseline in clinical ESSDAI scores were -3.74 points with placebo, -4.08 points with the low drug dose (not significant), and -6.40 points with the higher dose (P=0.002 relative to placebo). A gap first was apparent at week 4 and grew gradually as treatment went on. Clinical responses weren't measured at week 30, Noaiseh noted.

Other outcome measures included the Physician's Global Assessment (PhGA), regular ESSDAI with IgG included, the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI), as well as responder rates according to the and standards.

Week 24 results with 15-mg/kg nipocalimab relative to placebo for these endpoints were as follows:

• PhGA: -14.50 points (P<0.001)
• ESSDAI: -1.79 points (P=0.012)
• ESSPRI: -0.41 points (P=0.268)
• STAR: +23.7 percentage points (P=0.017)
• CRESS: +30.3 percentage points (P=0.001)

Noaiseh also reported that 20% more patients receiving the higher nipocalimab dose showed improvement of at least one level in at least one clinical ESSDAI domain, a "disease activity level" response.

Tracked over time, ESSPRI scores largely paralleled the trajectory seen with clinical ESSDAI, except that in the high-dose group, a slight rebound occurred in the treatment period's final 2 weeks such that the difference from placebo at week 24 fell short of statistical significance.

In every efficacy evaluation, the lower dose failed to show statistically significant superiority over placebo, although numerical advantages were usually visible.

Noaiseh also noted that, in line with the drug's IgG target, patients who were most strongly seropositive at baseline were the ones with the greatest clinical improvement.

About 80% of patients in the two nipocalimab groups experienced adverse events, compared with 63% of the placebo group. Infections accounted for most of the difference: these were seen in 60% of the low-dose and 52% of the high-dose groups, versus 43% of the placebo group. Severe infections were rare (four patients total) and spread across all three groups. Also, six of the nipocalimab patients had "activations of latent virus" (presumably herpes zoster) compared with one assigned to placebo. And infusion and hypersensitivity reactions were more common with the active agent.

Janssen, nipocalimab's developer, sees many potential applications beyond Sjögren's and myasthenia gravis. Trials are underway or completed in lupus and lupus nephritis, rheumatoid arthritis, and a number of rare diseases including fetal and neonatal alloimmune thrombocytopenia, warm autoimmune hemolytic anemia, chronic inflammatory demyelinating polyneuropathy, and a variety of idiopathic inflammatory myopathies.

It's also worth noting that nipocalimab is not the only drug around with FcRn as a target. Almost 3 years ago, the FDA approved efgartigimod (Vyvgart) to treat generalized myasthenia gravis. Instead of being a full-size antibody molecule like nipocalimab, it's a synthetic antibody fragment with the same action: binding to FcRn to prevent IgG recycling. Its developer has and that it plans a phase III study.

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