Johnson & Johnson released new data during the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress last week highlighting statistically significant findings in a phase 2 dose-range study on nipocalimab for Sjögren’s disease (SjD).
First, talk about SjD.
SjD is an autoimmune disorder that occurs when the immune system attacks the glands.
The ocular connection: A main symptom is dry eye disease (DED), which is caused by SjD attacking the exocrine glands of mucous membranes.
- On occasion, a DED diagnosis (measured via a Schirmer tear test) may precede other systemic symptoms of SjD by years.
And nipocalimab?
As a fully human monoclonal antibody, nipocalimab targets the neonatal crystallizable fragment receptor (FcRn) and, via administration, targets/binds to FsRn at the immunoglobulin G (IgG) binding site.
The result: Nipocalimab prevents any interaction between FcRn and IgG (a serum protein), with the intent to block any FcRn activity, allowing for IgG degradation while also preventing IgG-mediated inflammation.
Why this is key: IgG is noted for playing a critical role in autoimmune diseases (such as SjD) and is crucial in inflammatory processes.
What is nipocalimab being clinically studied for?
The antibody is currently under clinical investigation for three key areas in the autoantibody space:
- Rare autoantibody diseases
- Maternal Fetal diseases mediated by maternal alloantibodies
- Prevalent rheumatology (which includes SjD)
Its U.S. clinical status update:
- In February 2024: Nipcalimab was granted FDA Breakthrough Therapy Designation for hemolytic disease of the fetus and newborn (HDFN)
- In March 2024: The FDA granted Fast Track designation to nipocalimab for reducing the risk of fetal neonatal alloimmune thrombocytopenia (FNAIT) in alloimmunized pregnant adults
Gotcha. Now give me the rundown on this trial.
The randomized, placebo-controlled, double-blind, multicenter phase 2 DAHLIAS study evaluated the safety and efficacy of nipocalimab vs a placebo in adult (aged 18-75) SjD patients.
- Participants: 163 (see here for criteria)
- The setup: Participants randomized into three groups to receive:
- Nipocalimb (5 mg/kg): n =53
- Nipocalimb (15 mg/kg): n = 54
- Placebo: n = 56
- The dosings: Each dosage administered intravenously (IV) every 2 weeks through Week 22
- Note: Patients also received standard of care treatments (eye drops, artificial tears, saliva, punctum plugs, ec.) as well as/or one immunomodulator during the study period
And what was measured?
The primary outcome measure was change from baseline in Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) Score at Week 24.
- To know: This clinical index was designed to measure disease activity in patients with SjD
Details on the 15+ secondary outcome measures—measuring anywhere from baseline to Weeks 24, 30, and 36—can be found here.
Alrighty, now these findings.
Per the company: Patients who received nipocalimab 15 mg/kg demonstrated a greater than 70% relative average improvement on the primary endpoint compared to patients who received placebo.
The primary endpoint vs placebo details:
- Least squares (LS) mean difference for:
- Nipocalimab 15 mg/kg: –2.65; 90% (Confidence Interval [CI] –4.03, –1.28; p =0.002)
- Nipocalimab 5 mg/kg: –0.34; (90% CI, –1.71, 1.03; p =0.681)
- Placebo: -3.74 ( –4.74, –2.75)
Among secondary endpoints, similar improvements were also noted in the nipocalimab 15 mg/kg group vs placebo group (see here for those).
Any other improved measures?
Indeed … including patient-reported outcome measures, which were “numerically improved” in the nipocalimab 15 mg/kg group vs placebo group.
Interestingly, efficacy outcomes between these two groups were “generally similar,” according to investigators.
Plus: For both nipocalimab groups, significant dose-dependent reductions in IgG and autoantibodies were noted.
How about for dry eye-specific symptoms?
Yes! Improvements were also observed in eye dryness (as well as in mouth dryness and vaginal dryness).
Any adverse events?
Related adverse events (AEs)were observed among the following percentages:
- Nipocalimab 15 mg/kg: 33.3% of patients
- Nipocalimab 5 mg/kg: 39.6% of patients
- Placebo: 21.4% of patients
And serious AEs (SAEs) were also noted among the three groups:
- Nipocalimab 15 mg/kg: 7.4% of patients
- Nipocalimab 5 mg/kg: 7.5% of patients
- Placebo: 5.4% of patients
- Note: Specific AEs were not indicated.
Additionally: Severe infections/infections requiring IV anti-infectives were observed in 3.8% (nipocalimab 5 mg); 1.9% (nipocalimab 15 mg); and 1.8% (placebo) of patients.
- However: None were determined to be related to study treatment
So what’s the significance of this data?
The study authors noted that the DAHLIAS study is the first to analyze a FcRn blocker (nipocalimab) for SjD—as well as that nipocalimab is:
- Safe and well-tolerated (consistent with prior nipocalimab clinical studies)
- Leads to significant improvements vs placebo in the clinESSDAI index
“Together, these findings establish proof of concept for nipocalimab in SjD and support further evaluation in patients with moderate-to-severe [autoantibody]-positive SjD,” the authors concluded.
And the bigger picture?
These results are the first positive findings for nipocalimab to treat SjD—a disease with no cure—that mark potentially groundbreaking progress for a patient demographic with few treatment options.
“SjD patients need approved advanced therapies that can help address the serious health consequences of the disease,” stated Rerene Rooney, vice president of Rheumatology and Immunology Disease Area leader at Johnson & Johnson Innovative Medicine, “and I am encouraged by these results and the positive impact on disease measures that are clinically meaningful.”