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SAN DIEGO -- A focused treatment for IgG4-related disease may be on the way, if mid-stage study results presented here are replicated in pivotal trials.

In an open-label phase II study lasting 6 months and involving 15 patients with the often fatal condition, eight achieved remission after 2 months of treatment with Xmab-5871, an anti-CD19 monoclonal antibody, reported John H. Stone, MD, of Massachusetts General Hospital in Boston.

Although three patients were unable to complete the study because of adverse events (including disease progression), the remaining 12 all met the trial's primary endpoint, a minimum 2-point reduction from baseline in the multi-component IgG4-Related Disease Responder Index; the median score at baseline was 12 (range 2-30).

On the basis of these results, presented at the , drugmaker Xencor said it planned to begin a phase III trial in the second half of 2018.

IgG4-related disease is a rare B-cell disorder that affects multiple organ systems, often misdiagnosed as Sjögren's disease, lupus, sarcoidosis, or others, Stone explained in a late-breaker presentation. It's estimated to affect about 40,000 Americans. There are currently no approved therapies; patients are typically treated with corticosteroids. Rituximab (Rituxan) is sometimes used in cases not responding to steroids.

Xmab-5871 is humanized monoclonal antibody with the Fc subunit engineered to enhance its affinity for the Fc-gamma IIb receptor on B cells. In addition to IgG4-related disease, the drug is also in development for systemic lupus erythematosus and rheumatoid arthritis, . The goal is to inhibit but not completely eliminate B-cell lineage cells, Stone said.

In the current trial, patients received the drug by infusion every two weeks for a total of 24 weeks. The primary outcome measure was adapted from the Birmingham Vasculitis Activity Scale and the ANCA-Associated Vasculitis Scale, with investigators scoring activity in 25 organ domains; the scores for each are summed to yield a total Responder Index score.

All but one of the 15 patients showed involvement of at least two organ systems at baseline; one patient has 10 organ systems involved and 11 others from four to seven. The most common systems to be affected were the lymph nodes and the submandibular, parotid, and lacrimal glands.

Every patient with baseline scores above the median of 12 showed reductions much greater than the minimum of 2 points to qualify as meeting the primary endpoint. Eight achieved a Responder Index of 0 and had corticosteroids withdrawn, which was the definition of remission. The other four classified as responders also were able to stop steroid dosing and none had Responder Index scores greater than 4.

The drug had a quick onset of action as seen in sharp drops in mean B-cell and plasmablast counts after the second dose. The B-cell nadir was about 50% of baseline after eight doses; plasmablasts declined by 80%-90% from baseline and stayed suppressed. Stone said the significance of this latter finding was unclear -- it was not expected and whether it drives the clinical benefit or is actually an adverse effect is still under study.

Of the three patients dropping out before week 24, one initially responded but developed hypersensitivity at day 57; one showed no response after six doses and moved to rituximab (which was unsuccessful as well); and the third responded initially but relapsed by day 85. In at least one of these failures, anti-drug antibodies may have played a role, Stone said.