Voclosporin (Lupkynis): A Targeted Oral Pill for Lupus Nephritis
For many years, the treatment landscape for lupus nephritis—the inflammation of the kidneys caused by lupus—has relied on standard immunosuppressants and corticosteroids. However, the FDA's approval of Voclosporin in 2021 marked a significant turning point. Voclosporin is an oral calcineurin inhibitor, a type of immunosuppressant that works by blocking the activation of T-cells, which play a critical role in the immune system's attack on the kidneys. By suppressing this targeted immune response, Voclosporin can help protect kidney function, offering a more effective approach for patients with active lupus nephritis when used in combination with standard-of-care treatments.
How does Voclosporin improve outcomes?
Clinical trials for Voclosporin demonstrated its effectiveness in improving renal response rates compared to standard therapy alone. By achieving better control of the disease in the kidneys, it offers hope for preventing long-term organ damage and potentially end-stage kidney disease. Unlike other treatments, which have a broad immunosuppressive effect, Voclosporin's targeted mechanism makes it a key addition to a patient’s treatment plan for this specific and severe manifestation of lupus.
The Evolving Landscape of New Oral Lupus Medications
While Voclosporin is the newest FDA-approved oral medication, the pipeline for oral lupus therapies is robust, with several promising candidates in late-stage clinical trials.
Investigational oral JAK inhibitors
Janus Kinase (JAK) inhibitors are a class of small-molecule drugs that work by blocking specific signaling pathways inside immune cells, thereby reducing inflammation. While some JAK inhibitors are already approved for conditions like rheumatoid arthritis, their use in lupus is still under investigation. For example, Upadacitinib (Rinvoq), a selective JAK1 inhibitor, is currently in Phase III trials for SLE, with the potential to become a new oral option for patients. This represents a potential shift towards more targeted, oral small-molecule therapies that offer an alternative to injectables.
Oral molecular glues
Kangpu Biopharma's KPG-818 is another example of a new oral medication being developed. Described as a “molecular glue,” this small-molecule drug modulates immune signaling and is being evaluated in Phase IIb trials for cutaneous lupus, which primarily affects the skin. If successful, this could provide a better-tolerated alternative to systemic immunosuppressants for patients with chronic skin involvement.
New IV Biologics and Their Role in Treatment
It is important to distinguish new oral treatments from new biologic medications that are administered via intravenous (IV) infusion. The most prominent example is Anifrolumab (Saphnelo), another recent FDA-approved medication for moderate to severe SLE.
Anifrolumab (Saphnelo): An Infusion, Not a Pill
Anifrolumab is a monoclonal antibody that targets the type I interferon receptor, blocking a key signaling pathway involved in lupus inflammation. It is given as a 30-minute IV infusion every four weeks. Although it is a newer treatment, it is not an oral pill and thus serves a different patient population and treatment protocol than oral medications. The manufacturer is also exploring a subcutaneous version, which would be an injection rather than an infusion, but still not an oral pill.
Key differences: Pills vs. infusions
- Method of Administration: Oral pills are taken by mouth at home, while IV infusions require a visit to a medical facility or infusion center for administration.
- Targeting: Voclosporin is specific to lupus nephritis, whereas Anifrolumab is approved for general moderate to severe SLE.
- Mechanism: These newer therapies employ different mechanisms; Voclosporin inhibits calcineurin, while Anifrolumab inhibits the type I interferon receptor.
Comparison of New and Traditional Lupus Medications
| Feature | Voclosporin (Lupkynis) | Anifrolumab (Saphnelo) | Hydroxychloroquine (Plaquenil) | Oral Corticosteroids |
|---|---|---|---|---|
| Type | Oral pill (Calcineurin Inhibitor) | IV Infusion (Type I IFN Inhibitor) | Oral pill (Antimalarial) | Oral pill (Immunosuppressant) |
| Approval Year | 2021 | 2021 | Well-established | Well-established |
| Targeted Condition | Lupus Nephritis | Moderate to Severe SLE | Mild to Moderate SLE | Used for flares/inflammation |
| Mechanism | Blocks T-cell activation in kidneys | Blocks interferon pathway | Reduces autoantibodies | Suppresses inflammation broadly |
| Administration | Oral pill | IV Infusion (every 4 weeks) | Oral pill | Oral pill |
| Side Effects | Kidney function, high blood pressure | Infections (herpes zoster) | Retinal damage (rare), stomach upset | Weight gain, osteoporosis, mood changes |
Conclusion
While there is no single new pill for all lupus, the treatment landscape has seen significant and promising advancements. For the specific and serious complication of lupus nephritis, Voclosporin (Lupkynis) provides a targeted oral option approved in 2021. Simultaneously, other oral candidates like JAK inhibitors and molecular glues are moving through the pipeline, holding promise for the future. The approval of biologic infusions, such as Anifrolumab (Saphnelo), further diversifies treatment options for systemic lupus. These developments allow for a more personalized approach to lupus management, improving outcomes and offering renewed hope to patients. It is crucial for patients to have open conversations with their healthcare providers to determine which new and emerging treatment options, including the new pill for lupus nephritis, might be best suited for their individual needs. For more information, the Lupus Foundation of America provides extensive resources on both established and new medications.
