Chemistry:Dekavil

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Dekavil (also known as F8-IL10 or F8IL10) is an investigational immunocytokine developed by Philogen and currently licensed to Pfizer for the treatment of rheumatoid arthritis (RA).[1][2] The drug consists of a fully human fusion protein combining the F8 antibody, which targets the extra domain A (EDA) of fibronectin, with interleukin-10 (IL-10), an anti-inflammatory cytokine.[1] Dekavil is designed to selectively deliver IL-10 to sites of inflammation, thereby increasing the therapeutic index of the cytokine while minimizing systemic side effects.[1] The drug showed encouraging results in early clinical trials and, as of November 2025, remains in Phase 1 development under Pfizer's inflammation and immunology portfolio under investigation for the treatment of rheumatoid arthritis.[2]

Mechanism of action

Dekavil functioned as a targeted immunocytokine through a dual mechanism. The F8 antibody component specifically recognized and bound to the EDA domain of fibronectin, a protein that accumulates at sites of tissue remodeling and inflammation.[1] This antibody-mediated targeting allowed the fusion protein to selectively localize to inflamed synovial tissue in arthritic joints rather than distributing systemically throughout the body.

The IL-10 component provided the therapeutic effect. IL-10 is a potent immunoregulatory cytokine that inhibits the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interferon gamma (IFN-γ), while also suppressing antigen presentation and cell proliferation.[3] By concentrating IL-10 at the site of inflammation through antibody-mediated delivery, Dekavil aimed to enhance the anti-inflammatory effects while reducing the systemic exposure that limited the efficacy of recombinant IL-10 when administered alone.[1]

Medical uses

Dekavil was investigated as a potential treatment for patients with active rheumatoid arthritis who had failed to respond adequately to methotrexate (MTX) therapy and had previously failed at least one anti-TNF treatment.[4] This represented a particularly challenging patient population, as they had exhausted multiple lines of therapy and demonstrated resistance to conventional treatments.

Development history

The development of Dekavil emerged from comparative studies evaluating four different clinical-stage antibodies (L19, F16, G11, and F8) that target splice isoforms of fibronectin and tenascin-C for their ability to recognize synovial tissue changes in rheumatoid arthritis patients.[1] Among these candidates, the F8 antibody demonstrated the strongest and most homogeneous staining pattern in synovial biopsies from RA patients, making it the optimal choice for therapeutic development.[1]

The F8 antibody was fused to human IL-10 to create the immunocytokine. The fusion protein was produced in Chinese hamster ovary cells (CHO cells) and purified to homogeneity.[1] Both the antibody and cytokine components retained their biological activity after fusion, as demonstrated through binding assays on recombinant antigens and cell proliferation assays.[1]

Dekavil was originally developed by Philogen SpA, an Italian-Swiss biotechnology company based in Siena, Italy.[1] The clinical trials were conducted by Philogen,[2] and the product was subsequently licensed to Pfizer.[5] As of August 2025, Dekavil appears in Pfizer's clinical pipeline as a Phase 1 new molecular entity for rheumatoid arthritis within their inflammation and immunology portfolio.[2]

Clinical trials

Phase 1b study

A Phase 1b dose-escalation study was initiated to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of Dekavil in combination with methotrexate.[4] The study enrolled patients with active rheumatoid arthritis despite MTX therapy who had failed at least one anti-TNF treatment.[4][6]

The trial employed a standard 3+3 dose-escalation design with cohorts of 3 to 6 patients receiving escalating doses of Dekavil ranging from 6 μg/kg to 600 μg/kg, administered once weekly by subcutaneous injection for up to eight weeks, in combination with 10–15 mg of methotrexate.[7]

Dekavil demonstrated a favorable safety profile throughout the Phase 1b study. The drug was well tolerated up to the highest investigated dose of 600 μg/kg, and a maximum tolerated dose (MTD) was not reached.[7] Among 34 out of 35 patients treated in the study, no dose-limiting toxicity (DLTs), no serious adverse events (SAEs), and no suspected unexpected serious adverse reactions (SUSARs) were reported.[7]

Phase 2 study

Following the readout of Phase 1b results, a multicenter, randomized, double-blind, placebo-controlled Phase 2 trial was initiated.[7] The study enrolled patients with active RA despite MTX therapy who had failed anti-TNF treatment, consistent with the Phase 1b population.[8][9]

As of November 2025, this study has been terminated.

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 "Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine which inhibits the progression of collagen-induced arthritis". Arthritis Research & Therapy 11 (5). 2009. doi:10.1186/ar2814. PMID 19781067. 
  2. ↑ 2.0 2.1 2.2 2.3 "Pfizer Pipeline Q2 2025 Update". Pfizer. August 5, 2025. https://www.pfizer.com/science/drug-product-pipeline. 
  3. ↑ "Recent advances in dysphagia management". F1000Research 8: F1000 Faculty Rev–1549. 2019. doi:10.12688/f1000research.18688.1. PMID 31508201. 
  4. ↑ 4.0 4.1 4.2 "A phase IB clinical trial with Dekavil (F8-IL10), an immunoregulatory 'armed antibody' for the treatment of rheumatoid arthritis, used in combination wiIh methotrexate". The Israel Medical Association Journal 16 (10): 666. October 2014. PMID 25438467. https://www.ima.org.il/FilesUpload/IMAJ/0/95/47613.pdf. 
  5. ↑ "Delving into the Latest Updates on F8-IL10 with Synapse". https://synapse.patsnap.com/drug/c932383d8dcb4af180c9a51971a82032. 
  6. ↑ Philogen S.p.A. (2018-05-15). A Dose-finding, Pharmacokinetic Phase I Study of the Human Monoclonal Antibody-cytokine Fusion Protein F8IL10 (Dekavil) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis (Report). clinicaltrials.gov. https://clinicaltrials.gov/study/NCT02076659. 
  7. ↑ 7.0 7.1 7.2 7.3 "Update on the Clinical Phase 1 and Phase 2 Trials Investigating the Fully Human Immunocytokine Dekavil (F8IL10) in Patients with Rheumatoid Arthritis". American College of Rheumatology Annual Meeting. September 2017. https://acrabstracts.org/abstract/update-on-the-clinical-phase-1-and-phase-2-trials-investigating-the-fully-human-immunocytokine-dekavil-f8il10-in-patients-with-rheumatoid-arthritis/. 
  8. ↑ "FRI0118 Dekavil (F8IL10)–update on the results of clinical trials investigating the immunocytokine in patients with rheumatoid arthritis.". Annals of the Rheumatic Diseases. Annual European Congress of Rheumatology (EULAR) 77: 603–604. June 2018. doi:10.1136/annrheumdis-2018-eular.5550. https://www.researchgate.net/publication/330457402. 
  9. ↑ Philogen S.p.A. (2023-06-09). A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate Safety and Clinical Efficacy of Two Different Doses of F8IL10 (Dekavil) Administered Subcutaneously to Patients With Active Rheumatoid Arthritis Receiving Methotrexate. (Report). clinicaltrials.gov. https://clinicaltrials.gov/study/NCT02270632. 



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