Focus Sector: Autoimmune Research & Clinical Access

MISSION

The Flare audits unpublished, shelved, withdrawn, and terminated clinical trial data in the autoimmune and oncology sectors. We translate raw data into transparent briefings for patients, families, advocacy groups, and independent researchers.

April is Sjögren's Disease Awareness Month. This briefing covers what the disease actually is — including the symptoms most people do not know to connect to it — the 30-year gap in dedicated treatment, and where the drug pipeline stands right now. For the first time in the history of this disease, multiple late-stage programs are approaching FDA review simultaneously. The record on each is presented exactly as the data shows it.

Sjögren's disease is a chronic systemic autoimmune condition. The immune system attacks the body's moisture-producing glands — primarily the tear glands and salivary glands — causing the two symptoms most people recognize: dry eyes and dry mouth. But those two symptoms are the surface. Beneath them is a disease that can affect nearly every organ system in the body.

It is the second most prevalent rheumatic autoimmune disease in the United States, affecting an estimated four million Americans. Approximately 90% of diagnosed patients are women. It can appear at any age, though diagnosis most commonly occurs between ages 40 and 60. It frequently presents alongside or is mistaken for other conditions, contributing to an average diagnostic delay of 4.5 years.

The cause is not fully established. Researchers have identified genetic susceptibility factors — particularly HLA class II gene variants — combined with environmental triggers that may initiate or accelerate the autoimmune response. The mechanism involves B-cell hyperactivation and lymphocytic infiltration of exocrine glands, which is why most of the current drug pipeline targets B-cell pathways.

This is the section that matters most for awareness month. Sjögren's is a systemic disease. The following are documented manifestations that are frequently attributed to other causes, missed entirely, or discovered only after years of unexplained symptoms.

Neuropathy — numbness and tingling Peripheral nerve involvement occurs in a documented subset of Sjögren's patients. This can present as numbness or tingling in the hands and feet, burning pain in the extremities, or in more severe cases, loss of coordination and balance (sensory ataxic neuropathy). Many patients are evaluated for multiple sclerosis or diabetes-related neuropathy before Sjögren's is considered.

Brain fog In a 2021 patient survey, 54% of Sjögren's patients reported brain fog as having a major or moderate impact on their life. It is not a recognized symptom in most standard diagnostic checklists.

Lung involvement Up to 20% of Sjögren's patients develop respiratory involvement, including a persistent dry cough, recurrent sinusitis, bronchitis, or in more serious cases, interstitial lung disease. A chronic dry cough in a patient with other sicca symptoms warrants evaluation.

Kidney involvement Sjögren's can affect the renal tubules — the filtering structures of the kidney. This often produces no noticeable symptoms until bloodwork or urinalysis reveals abnormalities such as changes in urine pH, low potassium, or kidney stones. Foamy urine is one of the few patient-detectable signals.

Lymphoma risk This is the most serious long-term complication and the least discussed. Sjögren's patients are 44 times more likely to develop non-Hodgkin lymphoma than the general population. After 20 years of disease, close to one in five patients will develop lymphoma. The most common types are MALT lymphoma of the salivary glands and diffuse large B-cell lymphoma. Unexplained swelling of lymph nodes in the neck, armpits, or groin in a Sjögren's patient warrants prompt evaluation.

Vaginal dryness Documented and frequently unreported. Affects quality of life significantly and is rarely raised in standard rheumatology appointments unless the patient raises it first.

Dental deterioration Saliva is protective. Without adequate saliva flow, cavity rates accelerate dramatically, often affecting the roots and gumline in patterns that dentists can recognize as a possible sicca-related presentation.

Raynaud's phenomenon Exaggerated blood vessel response to cold or stress — fingers and toes turning white or blue — occurs in a subset of Sjögren's patients and is frequently attributed to other causes or dismissed as a standalone condition.

Research consistently shows that 5% to 12% of Sjögren's patients have celiac disease, compared to approximately 1% of the general population. Most of them do not know it.

Here is why this matters practically: celiac disease is frequently silent. It does not always cause obvious gastrointestinal symptoms. What it does cause — iron deficiency without clear explanation, unexplained osteoporosis, peripheral neuropathy, and a blunted response to hepatitis B vaccination — can look like Sjögren's disease activity or an unrelated finding.

The hepatitis B titer connection is specific and underreported. Celiac disease impairs nutrient absorption in the small intestine including the immune response to vaccines. A Sjögren's patient who shows low or non-protective hepatitis B antibody titers after a standard vaccination series should be screened for celiac disease — not simply re-vaccinated. The mechanism is intestinal villous atrophy reducing immune responsiveness, not a problem with the vaccine itself.

The recommended screening test is a tissue transglutaminase IgA (tTG-IgA) blood test. Multiple published researchers and the Sjögren's Foundation's own clinical guidance recommend that all Sjögren's patients be screened for celiac disease regardless of gastrointestinal symptoms, because the consequences of undiagnosed celiac — including a compounded lymphoma risk — are significant in this population.

Until this year, there was no FDA-approved disease-modifying therapy specifically for Sjögren's disease. The treatments available — artificial tears, cyclosporine eye drops, hydroxychloroquine, and corticosteroids — address symptoms or are borrowed from other autoimmune conditions. None of them modify the underlying disease process or reduce the lymphoma risk.

This is not because Sjögren's is rare. Four million Americans carry the diagnosis and the true number is likely higher. It is in part because the disease was historically framed as a condition of dryness rather than a systemic autoimmune disease, and in part because the clinical trial endpoints — how you measure whether a drug is actually working — took decades to standardize. The ESSDAI scoring tool, now the universal primary endpoint in Sjögren's trials, was not developed until the early 2010s. Without a validated measurement tool, trials could not be designed with enough scientific rigor to support regulatory approval.

That measurement problem is now solved. And the pipeline that has built up behind it is the most active this disease has ever seen.

Status: FDA Breakthrough Therapy Designation granted January 16, 2026. Regulatory submission filed globally starting early 2026.

What it is: A monthly subcutaneous injection that works by depleting overactive B cells and blocking the signal that keeps those cells active. Two Phase 3 trials — NEPTUNUS-1 and NEPTUNUS-2 — enrolled a combined 779 patients across 35 countries. Both met their primary endpoint, showing statistically significant reductions in disease activity at week 48 compared to placebo. If approved, it would be the first drug ever specifically approved for Sjögren's disease.

What families should know: Regulatory submission has been filed. The FDA review process under Breakthrough Therapy Designation involves expedited review, but approval is not guaranteed and a timeline for a final decision has not been publicly stated. This is the program to watch most closely in 2026.

Status: Phase 3 DAFFODIL trial (NCT06741969) — active, not recruiting as of March 2026. Enrollment has closed. The trial is ongoing with participants already enrolled. FDA granted both Breakthrough Therapy and Fast Track Designation.

What it is: A subcutaneous injection that works differently from ianalumab. Rather than targeting B cells directly, it reduces the levels of the self-reactive antibodies — specifically IgG antibodies — that drive Sjögren's immune damage, by blocking the receptor that normally recycles them. In Phase 2, the higher dose produced greater than 70% reduction in systemic disease activity scores over 24 weeks. The trial is enrolling up to 600 participants across the U.S., Europe, Middle East, Asia, and South America.

What families should know: New enrollment is closed at this time. The trial record and J&J's trial page remain worth monitoring — enrollment status can reopen if sites add capacity or if a participant withdraws. Check back periodically.

Status: Phase 3 HZNP-DAZ-303 trial (NCT06245408) — active, not recruiting as of January 2026. Enrollment has closed. Trial ongoing with participants already enrolled. Expected completion late 2026.

What it is: A monthly IV infusion that blocks the signal between T cells and B cells — interrupting the immune coordination that drives Sjögren's inflammation. This trial was specifically designed for patients with high symptom burden — significant dryness, fatigue, and pain — but lower systemic disease activity scores. That patient population has historically been excluded from Sjögren's trials, making this program notable regardless of enrollment status.

What families should know: New enrollment is closed at this time per the public record. The trial record is worth monitoring as status can change. Results are expected late 2026.

Status: Phase 3 POETYK SjS-1 trial (NCT05946941) — active, not recruiting. Confirmed via ClinicalTrials.gov. Enrollment has closed. Trial is ongoing with participants already enrolled.

What it is: An oral pill — already FDA-approved for psoriasis — being tested over 52 weeks in Sjögren's patients. Targets a different set of immune signals than the other programs above.

What families should know: This was the only oral option in Phase 3. Enrollment is closed at this time. Monitor the ClinicalTrials.gov record directly for any status changes.

Status: Phase 3 UNITY trial (NCT06684847) actively recruiting — approximately 580 participants across 306 sites worldwide. FDA granted Fast Track designation in early 2025. Results anticipated late 2026-2027.

What it is: A weekly subcutaneous injection already approved under the brand name Vyvgart Hytrulo for myasthenia gravis. In Sjögren's, it works by blocking a receptor called FcRn — the same general mechanism as nipocalimab — which accelerates the breakdown of self-reactive IgG antibodies driving immune damage. In a Phase 2 proof-of-concept study, 45.5% of patients on efgartigimod improved meaningfully on a composite disease measure versus 11.1% on placebo. The Phase 3 UNITY trial runs 48 weeks with an optional open-label extension.

Who may qualify (key criteria)

Where to apply or express interest

The tTG-IgA Test — What It Is and When to Ask for It

Tissue transglutaminase IgA (tTG-IgA) is the primary blood screening test for celiac disease. It detects IgA antibodies that form in response to gluten exposure in people with celiac disease. The test is highly sensitive — it is positive in approximately 95% of people with untreated celiac disease. A positive result requires confirmation with a duodenal biopsy, but the blood test alone is sufficient to initiate further evaluation. For Sjögren's patients specifically, this test is recommended by multiple clinical researchers regardless of gastrointestinal symptoms, because celiac disease in this population is frequently silent and the risks of leaving it undiagnosed — compounded lymphoma risk, nutrient malabsorption, poor vaccine response — are clinically significant.

Sjögren's Foundation Virtual National Patient Conference 2026 Date: April 10–11, 2026 Format: Virtual — open nationally Register: sjogrens.org/get-involved/national-patient-conference

International Symposium on Sjögren's Disease 2026 Date: September 29, 2026 — Paris, France

The Flare is an independent investigative journalism outlet. We are not medical providers, clinical trial sites, or financial advisors. This information is for educational and journalistic purposes only and does not constitute medical advice. Individuals seeking guidance on clinical trial eligibility, screening tests, or treatment decisions should consult a licensed physician or rheumatologist.