Forigerimod
The lupus peptide Lupuzor: a promising phase 2b result, then a phase 3 trial that did not separate from placebo
Forigerimod, better known as Lupuzor or the P140 peptide, is a 21-amino-acid fragment of a spliceosome protein with one phosphorylated serine. In lupus-prone mice it calmed the disease and lengthened survival, apparently by slowing an overactive form of autophagy in immune cells rather than by suppressing immunity. A phase 2b trial in 149 people with lupus looked encouraging, but the 52-week phase 3 trial of 202 patients found 52.5% responders on the drug against 44.6% on placebo, a difference that was not statistically significant. It has not been approved.
Used in human trials: 200 mcg, Every 4 weeks (3 doses), Subcutaneous (Phase 2b, 149 patients: four-weekly arm) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
Forigerimod is a short synthetic peptide copied from a protein that people with lupus often make antibodies against: U1-70K, part of the spliceosome, the machinery that edits RNA inside the cell nucleus. The fragment runs from position 131 to 151 and carries a phosphate group on the serine at position 140, which is where the name P140 comes from. Its discoverers reported in 2003 that lupus-prone MRL/lpr mice given the phosphorylated version had less protein in their urine, fewer anti-DNA antibodies and longer lives, while the same sequence without the phosphate did nothing. The drug was developed as Lupuzor by ImmuPharma under the code IPP-201101.
How it works was worked out step by step in mice and in human cells. P140 binds the chaperone protein HSPA8, also called HSC70, enters immune cells through the endosome route and collects inside lysosomes. There it slows chaperone-mediated autophagy, a recycling pathway that runs too fast in lupus-prone mice, and lowers the levels of two of its key proteins, LAMP2A and HSPA8. The result described in these studies is less loading of self-antigens onto MHC class II molecules, so fewer autoreactive T cells are switched on. In B cells from people with lupus, P140 reduced the excess HLA class II on their surface and held back their maturation into antibody-secreting plasma cells. Its developers describe it as an immune regulator rather than an immunosuppressant.
The human trials began with an open-label study of 20 Bulgarian patients in 2008: three injections of 200 micrograms lowered anti-DNA antibodies by at least a fifth in 7 of 10, while a fivefold higher dose did little. A randomised phase 2b trial of 149 patients followed. Given every four weeks on top of standard care, 53.1% of patients met the SLE Responder Index at week 12 against 36.2% on placebo; the every-two-weeks group, at 45.1%, did not differ significantly from placebo. The developers later linked part of the variation to the formulation: a version made with the sugar trehalose, itself an autophagy activator, did worse than one made with mannitol.
The phase 3 trial, NCT02504645, tested the four-weekly 200-microgram dose for 48 weeks in 202 patients. According to the results posted on ClinicalTrials.gov, 52.5% responded on forigerimod and 44.6% on placebo at week 52, with a p-value of 0.26, so the trial missed its primary endpoint. A post hoc look at European patients who had anti-double-stranded-DNA antibodies at the start found 61.5% against 47.3%, but a subgroup chosen after the results were known cannot rescue a failed trial. A 2023 review in the Annals of the Rheumatic Diseases groups rigerimod with epratuzumab, baricitinib and ustekinumab as lupus drugs whose phase 2 promise did not hold up in phase 3. Serious adverse events were similar in both arms, and no deaths were reported.
Since then the research has moved back to animals. The same group has tested P140 in mouse models of gout, periodontitis, airway allergy, colitis and glioblastoma, reporting benefits in each. Not every result points the same way: a 2023 study in a different, imiquimod-induced mouse model of lupus reported that P140 drew macrophages into the lungs and was followed by lung fibrosis and worse disease. Forigerimod is not approved by the FDA, the EMA or any regulator we found, and is not something a person can obtain outside a trial.
Mechanism of Action
P140 acts on autophagy, the cell's recycling system, in immune cells. The studies below place its action on the chaperone HSPA8 and on chaperone-mediated autophagy, which feeds self-antigens to MHC class II molecules.
Binding HSPA8 (HSC70)
P140 binds the constitutively expressed chaperone HSC70 and, in lupus-prone mice, triggered apoptosis of activated CD4 T cells through a route that needed gamma-delta T cells (2009 study).
Slowing chaperone-mediated autophagy
Inside lysosomes it lowered LAMP2A and HSPA8 and blocked the uptake of autophagy substrates, the step that runs too fast in lupus-prone mice (2015 and 2020 studies).
Less self-antigen on MHC class II
In human lupus B cells it reduced HLA class II overexpression and the maturation of B cells into IgG-secreting plasma cells, without changing B-cell receptor signalling (2018 study).
Clearing overactive lymphocytes
In treated lupus-prone mice, hyperactivated autoreactive T and B cells disappeared from lymphoid tissue and blood, which the authors read as clearance rather than suppression (2022 study).
Published Research
These are the studies of P140 read from their PubMed abstracts on October 29, 2026: three trials in people with lupus, three studies in human or mouse cells, nine in mice, and three reviews. Almost all come from the group that discovered the peptide and its partners. Several titles call it only 'a phosphopeptide' or 'a therapeutic peptide'; those are carded because their abstracts name P140 as the substance tested. The phase 3 trial has no peer-reviewed abstract we could find, so its results are taken from ClinicalTrials.gov and cited there.
Phase 2b: 149 patients with lupus
Patients on standard care were randomised to 200 micrograms under the skin every four weeks, every two weeks, or placebo. At week 12, 53.1% of the four-weekly group met the SLE Responder Index against 36.2% on placebo (p = 0.048); the two-weekly group reached 45.1%, not significantly different. In patients with clinically active disease the four-weekly figure was 61.9% against 38.6%. The commonest side effect was mild redness at the injection site.
First trial: 20 patients in Bulgaria
An open-label, dose-escalation phase 2 study gave three injections two weeks apart. Anti-DNA antibodies fell by at least 20% in 7 of 10 patients on 200 micrograms but in only 1 on 1,000 micrograms, and disease-activity scores fell significantly in the lower-dose group. The only adverse effect reported was local irritation at the higher dose.
Two phase 2b formulations compared
The developers describe two successive phase 2b trials in lupus that used P140 made up with different excipients, mannitol or trehalose. Trehalose is reported to stimulate autophagy, and the authors argue it worked against the peptide, whose aim is to damp excessive autophagy in immune cells.
B cells from people with lupus
In human immune cells studied outside the body, P140 entered B cells by clathrin-dependent endocytosis and went to lysosomes. It left B-cell receptor signalling alone but cut the overexpression of HLA class II on lupus B cells, slowed their maturation into plasma cells, and lowered IgG secretion.
Neutrophils and NETs: no direct effect
In human neutrophils and in normal and lupus-prone mice, P140 did not change the formation of neutrophil extracellular traps, cytokine output, or chaperone-mediated autophagy in neutrophils. The authors conclude its benefit in lupus is not explained by acting on neutrophils.
Mitochondria and NET release
In isolated mitochondria and live cells, P140 had little if any effect on the autophagy of mitochondria, while acting on macroautophagy and chaperone-mediated autophagy. It did suppress the release of extracellular traps from neutrophils exposed to complexes of traps and anti-DNA antibodies.
The discovery in lupus-prone mice
Of two phosphorylated versions of the U1-70K fragment, the one phosphorylated at serine 140 was recognised by T cells and antibodies from MRL/lpr mice. Given intravenously in saline it lowered proteinuria and anti-DNA antibodies and significantly prolonged survival; the unphosphorylated peptide did not. It was also recognised by antibodies from lupus patients.
HSC70 identified as its receptor
P140 bound the chaperone HSC70 on the cell surface and induced apoptosis of activated CD4 T cells from MRL/lpr mice. In treated mice it lowered counts of B cells and activated T cells through a mechanism that depended on gamma-delta T cells, and rapidly changed inflammation-linked gene expression.
Where it goes and what it blocks
In imaging studies the peptide accumulated mainly in the lungs and spleen of mice. It reduced T- and B-cell numbers in lupus-prone mice but not in normal mice, lowered HSC70 and stable MHC class II levels in B cells, and impaired HSC70's refolding activity, slowing autophagic flux.
Chaperone-mediated autophagy as the target
In B cells from lupus-prone mice, P140 inhibited chaperone-mediated autophagy and reduced LAMP2A, the rate-limiting component that is raised in these cells. Only the phosphorylated peptide reached the lysosome lumen by the endo-lysosomal route, where the authors propose it disturbs HSPA8 and destabilises LAMP2A.
Autophagy corrected inside the body
Given intravenously to MRL/lpr mice, P140 lowered chaperone-mediated autophagy at the step where substrates are taken up into lysosomes, and restored some defects of lysosomes isolated from the spleen and liver.
Autoreactive cells cleared in lupus mice
In P140-treated lupus-prone mice the T- and B-cell abnormalities of the disease were no longer seen in secondary lymphoid tissue or blood. The data point to removal of hyperactivated autoreactive cells rather than suppression of the immune system as a whole.
A contrary result in another lupus model
In B6 mice with imiquimod-induced lupus, P140 was followed by a heavy build-up of CX3CR1-positive macrophages in the lungs and by lung fibrosis, with more reactive oxygen species and citrullinated histone H3. The authors conclude it aggravated lupus in this model, a disease the antioxidant apocynin prevented.
Gout in mice
In mice injected with uric-acid crystals, P140 reduced pain sensitivity, neutrophil influx and inflammatory cytokines, increased the pro-resolving protein annexin A1, and lowered ATG5-ATG12 and HSPA8. It also acted on human neutrophils treated with the crystals.
Periodontitis and bone loss in mice
In mice with ligature-induced periodontitis, ten days of intraperitoneal P140 normalised several autophagy genes, reduced activated lymphocytes and inflammatory cytokines, and lessened jaw bone loss compared with a scrambled control peptide.
From P140 to Lupuzor
A review in a French pharmacy journal traces the peptide from its discovery in lupus-prone mice to the multicentre phase 2b trials, and notes that its future depended on whether a second phase 2b and a phase 3 trial confirmed the first.
The developers' account before phase 3
Written as phase 3 was about to begin, this review gives the phase 2b interim analysis: disease-activity improvement in 67.6% on the drug against 41.5% on placebo after three months, and 84.2% against 45.8% three months later. It describes P140 as a fine modulator of CD4 T cells, not an immunosuppressant.
Why lupus phase 3 trials fail
A review in the Annals of the Rheumatic Diseases examines phase 2 and 3 trials of epratuzumab, baricitinib, rigerimod (the P140 peptide) and ustekinumab, all of which failed to confirm in phase 3 the promise of their phase 2 results, and discusses why phase 2 can mislead.
Dosing Data
Forigerimod has no approved label anywhere. The rows below are the amounts given in the published lupus trials, always on top of patients' standard lupus treatment. The phase 3 trial registered on ClinicalTrials.gov (NCT02504645) gave the same 200 micrograms every four weeks, 13 doses over 48 weeks, and found no significant benefit over placebo.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Forigerimod is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
An arithmetic example, not a recommendation: a 5 mg vial mixed with 2 mL of bacteriostatic water holds 2,500 mcg per mL, so every 10 units on a U-100 insulin syringe hold 250 mcg. 200 mcg, the “Phase 2b, 149 patients: four-weekly arm” row is 8.0 units (0.080 mL). If your vial or water differ, the numbers change: use the reconstitution calculator.
Source: dose: Used in human trials, PMID 23172751 (Dosing Data below); vial and water: the calculator's default example, not a vial size we have a source for.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Forigerimod, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Forigerimod stays intact once mixed.
How it is taken
As it was given in human studies: Subcutaneous (Every 4 weeks (3 doses); Phase 2b, 149 patients: four-weekly arm).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Phase 2b, 149 patients: four-weekly arm: 12 weeks, followed to week 24; Phase 2b, 149 patients: two-weekly arm: 12 weeks; Open-label phase 2, 20 patients: two dose groups: About 4 weeks.
When effects appear: unknown; no source on this page gives a time to effect for Forigerimod. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Mild redness at the injection site was the commonest side effect in phase 2b (PMID 23172751); Local irritation at 1,000 micrograms, not at 200, in the first open-label trial (PMID 19035498); Phase 3: serious adverse events in 13 of 101 patients on forigerimod and 16 of 101 on placebo; no deaths (ClinicalTrials.gov NCT02504645); In one mouse model of lupus it was followed by lung fibrosis and worse disease (PMID 37922035). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Forigerimod. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials above and the posted phase 3 results”).
Interactions
Unknown: a PubMed search for human interaction studies of Forigerimod (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Forigerimod products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Forigerimod's expected mass, 2,638.9 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Not FDA Approved (Not approved anywhere we found: Drugs@FDA and the EMA medicines list hold no record (searched October 28, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the trials above and the posted phase 3 results.
Contraindications & Cautions
No approved label exists, so there are no official contraindications. Points from the evidence:
Legal Status
Forigerimod is investigational and has not been approved by any regulator we checked.
Frequently Asked Questions
?What is forigerimod?
A synthetic 21-amino-acid peptide, also called Lupuzor or P140, copied from the U1-70K spliceosome protein with a phosphate on serine 140. It was developed as a lupus treatment that acts on autophagy in immune cells.
?Did Lupuzor work in lupus?
A phase 2b trial reported 53.1% responders on the four-weekly dose against 36.2% on placebo at 12 weeks. The larger 52-week phase 3 trial then found 52.5% against 44.6%, which was not statistically significant, so it missed its main goal.
?Is it an immunosuppressant?
Its developers say no. In mice and human cells it damped an overactive autophagy pathway and the presentation of self-antigens rather than suppressing immune responses in general.
?What dose was used?
200 micrograms injected under the skin every four weeks in phase 3, and every two or four weeks in phase 2b, always with standard lupus treatment. These were trial amounts; there is no approved dose.
?Can I buy forigerimod?
It is not approved anywhere and has only been given in clinical trials. Anything sold under the name online has not been checked by any regulator.
References
- [other] PubChem CID 56841982, Forigerimod: formula C117H181N34O32PS, molecular weight 2638.9. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/56841982
- [clinical-trial] Zimmer R, et al. "Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial." Ann Rheum Dis, 2013;72(11):1830-5. PMID: 23172751.
- [clinical-trial] Muller S, et al. "Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial." Arthritis Rheum, 2008;58(12):3873-83. PMID: 19035498.
- [clinical-trial] Muller S. "Excipients: not so inert? When the excipient plays the role of an active substance, as exemplified by systemic lupus." Swiss Med Wkly, 2018;148:w14631. PMID: 29964292.
- [pubmed] Wilhelm M, et al. "Lupus Regulator Peptide P140 Represses B Cell Differentiation by Reducing HLA Class II Molecule Overexpression." Arthritis Rheumatol, 2018;70(7):1077-1088. PMID: 29499102.
- [pubmed] Maueröder C, et al. "Capability of Neutrophils to Form NETs Is Not Directly Influenced by a CMA-Targeting Peptide." Front Immunol, 2017;8:16. PMID: 28191006.
- [pubmed] Bendorius M, et al. "The Mitochondrion-lysosome Axis in Adaptive and Innate Immunity: Effect of Lupus Regulator Peptide P140 on Mitochondria Autophagy and NETosis." Front Immunol, 2018;9:2158. PMID: 30319621.
- [pubmed] Monneaux F, et al. "T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MR/lpr mice." Eur J Immunol, 2003;33(2):287-96. PMID: 12548559.
- [pubmed] Page N, et al. "The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells." PLoS One, 2009;4(4):e5273. PMID: 19390596.
- [pubmed] Page N, et al. "HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus." Ann Rheum Dis, 2011;70(5):837-43. PMID: 21173017.
- [pubmed] Macri C, et al. "Modulation of deregulated chaperone-mediated autophagy by a phosphopeptide." Autophagy, 2015;11(3):472-86. PMID: 25719862.
- [pubmed] Wang F, et al. "In Vivo Remodeling of Altered Autophagy-Lysosomal Pathway by a Phosphopeptide in Lupus." Cells, 2020;9(10). PMID: 33092174.
- [pubmed] Schall N, et al. "P140 Peptide Leads to Clearance of Autoreactive Lymphocytes and Normalizes Immune Response in Lupus-Prone Mice." Front Immunol, 2022;13:904669. PMID: 35720371.
- [pubmed] Zhong J, et al. "Phosphopeptides P140 cause oxidative burst responses of pulmonary macrophages in an imiquimod-induced lupus model." Mol Biomed, 2023;4(1):38. PMID: 37922035.
- [pubmed] Galvão I, et al. "The Therapeutic Effect of Phosphopeptide P140 Attenuates Inflammation Induced by Uric Acid Crystals in Gout Arthritis Mouse Model." Cells, 2022;11(23). PMID: 36496970.
- [pubmed] Akiyama K, et al. "Therapeutic effects of peptide P140 in a mouse periodontitis model." Cell Mol Life Sci, 2022;79(10):518. PMID: 36104457.
- [review] Muller S. "[Novel strategy in lupus therapy: from the peptide P140 to Lupuzor™]." Ann Pharm Fr, 2011;69(3):151-4. PMID: 21570539.
- [review] Schall N, et al. "Resetting the autoreactive immune system with a therapeutic peptide in lupus." Lupus, 2015;24(4-5):412-8. PMID: 25801884.
- [review] Lorenzo-Vizcaya A, et al. "Clinical trials in systemic lupus erythematosus: the dilemma-Why have phase III trials failed to confirm the promising results of phase II trials?." Ann Rheum Dis, 2023;82(2):169-174. PMID: 36202589.
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT02504645 (phase 3, completed), NCT01240694 (phase 3 long-term safety, terminated) and NCT01135459 (phase 2, completed).
- [registry] ClinicalTrials.gov NCT02504645 (ImmuPharma, IPP-201101/005), results posted April 11, 2019, read October 29, 2026: 202 patients treated (101 per arm), 200 mcg or placebo under the skin every 4 weeks for 48 weeks with standard of care; SLE Responder Index at week 52 52.5% versus 44.6%, p = 0.2631; serious adverse events 13 of 101 versus 16 of 101; no deaths. https://clinicaltrials.gov/study/NCT02504645
Sources & Citations
Studies were read from their PubMed records on October 29, 2026. The phase 3 results are from the results section of ClinicalTrials.gov record NCT02504645, posted by the sponsor ImmuPharma on April 11, 2019 and read October 29, 2026. Regulatory status comes from Drugs@FDA and the EMA medicines list, searched October 28, 2026. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.