Quick answer
Primary membranous nephropathy is a common cause of nephrotic syndrome in adults, driven by autoantibodies — most often against the phospholipase A2 receptor — produced by B cells. Rituximab works, but a substantial share of patients do not respond, and the disease progresses to kidney failure in roughly a third within a decade. MIL62 is a third-generation anti-CD20 antibody engineered for deeper B-cell depletion. Cui Zhao's team at Peking University First Hospital led the phase 3 trial across 32 Chinese centres. At 76 weeks, 49.4% of patients on MIL62 achieved complete remission, against 3.9% on cyclosporine. The results were presented at the American Society of Nephrology meeting on 8 November 2025 [1][3][6].
Key takeaways
- Design: multicentre, randomised, open-label, active-controlled phase 3 trial (MIL62-CT307) [1][5].
- Population: 153–154 patients with biopsy-proven primary membranous nephropathy across 32 Chinese centres [1][5].
- Regimen: MIL62 1,000 mg intravenously at weeks 1, 3, 25, 27 and 53, versus cyclosporine titrated to a trough of 125–175 ng/mL for 52 weeks [5].
- Primary endpoint: complete remission at week 76 — 49.4% versus 3.9% [1][2].
- Described as the first phase 3 registration trial in this disease globally to meet its primary endpoint [2][4].
Why the antibody was engineered, not just chosen
Rituximab is a first-generation anti-CD20 antibody; obinutuzumab is second; MIL62 is third. Its fucose residues are removed almost completely, which raises affinity for the activating Fc receptor FcγRIIIa and strengthens antibody-dependent cellular cytotoxicity. The clinical intention is deeper and more sustained depletion of B cells in tissue, not just in blood — and the hope is immune reset rather than continuous suppression [1][5].
The reported immunological response supports the mechanism: at week 76, immunological remission reached 87.5%, meaning most patients cleared their pathogenic antibody even when proteinuria had not yet fully resolved — the two endpoints move on different timescales in this disease [6].
Reading a 49.4% versus 3.9% result
The comparison is against cyclosporine, a calcineurin inhibitor that suppresses proteinuria rather than treating the underlying autoimmunity, and which is known to have high relapse rates on withdrawal. A large separation is therefore expected, and the more informative comparator would have been rituximab [1][4].
The trial was open-label, so neither patients nor investigators were blinded to treatment, which matters for a disease where proteinuria can fluctuate with blood pressure, diet and adherence. Complete remission at 76 weeks is a validated surrogate, but the outcomes that decide a patient's future — progression to kidney failure, relapse after stopping, and long-term safety of sustained B-cell depletion — need years more follow-up. The absence of a rituximab arm means the trial establishes superiority over an older standard, not over current best practice. Results were presented at a conference and the full peer-reviewed publication should be read before practice changes [2][5].
The condition in context: membranous nephropathy
It is the commonest cause of adult nephrotic syndrome in China, and its incidence is rising.
| Region | What the data shows | Source |
|---|---|---|
| Trajectory | Prevalence in China is rising at about 13% a year; roughly a third progress to kidney failure [2]. | Yisheng via Toutiao [2] |
| Mechanism | B-cell-derived autoantibodies drive the glomerular lesion, which is why B-cell depletion works [2]. | Yisheng via Toutiao [2] |
| Unmet need | A substantial proportion do not respond adequately to first-generation anti-CD20 therapy [2]. | Yisheng via Toutiao [2] |
Because the disease is antibody-driven, a therapy that achieves durable immunological remission addresses cause rather than symptom [1][5].
Why it matters
| Potential | What the report suggests | Source |
|---|---|---|
| Efficacy | 49.4% versus 3.9% complete remission at 76 weeks [1][2]. | [1][2] |
| Immunological remission | 87.5% at week 76 [6]. | [6] |
| Caution | Open-label; comparator is not rituximab [4][5]. | [4][5] |
Availability and limits
- This is an editorial summary of a conference presentation, not a treatment recommendation [1][3].
- MIL62 is investigational and not approved [4].
- Open-label design and an active comparator that is no longer first choice [5].
- Relapse after stopping and long-term safety are unknown [2].
- Full peer-reviewed publication is awaited [3].
What to ask before booking
| Question | Why it matters |
|---|---|
| Has my anti-PLA2R antibody status been measured? | It defines the disease and monitors response [2]. |
| Is MIL62 available outside a trial? | No — it is investigational [4]. |
| Which department handles foreign patients, and in what language? | The hospital is a working hospital we do not book; confirm international-department coordination and language support. |
| What is the plan if I do not respond to anti-CD20 therapy? | Alternatives exist and should be discussed up front [5]. |
Questions patients ask
What was tested?
MIL62, a third-generation glycoengineered anti-CD20 antibody, versus cyclosporine in 154 patients with biopsy-proven primary membranous nephropathy across 32 Chinese centres [1][5].
What was the result?
Complete remission at week 76 was 49.4% with MIL62 versus 3.9% with cyclosporine; immunological remission reached 87.5% [1][6].
Why is this notable?
It is described as the first phase 3 registration trial in primary membranous nephropathy globally to meet its primary endpoint [2][4].
Is MIL62 available?
Not yet — it is investigational pending approval [4].
Is this relevant to international patients?
It is useful context for China's nephrology research. The hospital is a working hospital we do not book — contact its international department directly [1].