Artikel
DEKAVIL (F8IL10): A novel therapeutic approach for the treatment of rheumatoid arthritis
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Veröffentlicht: | 4. September 2017 |
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Background: The antibody-based targeted pharmacodelivery of cytokines by means of immunocytokines has the potential to enhance therapeutic activity at the site of disease while sparing healthy tissues. Dekavil (F8IL10) is a fully human immunocytokine composed of the vascular targeting antibody F8 (specific to EDA) fused to the cytokine interleukin-10. Dekavil is currently in phase 2 clinical development for the treatment of rheumatoid arthritis (RA).
Methods: Patients with active RA despite methotrexate therapy (MTX, stable doses of 10- 25 mg/week), who failed anti-TNF treatment receive a maximum of eight weekly subcutaneous injections of Dekavil. The recently completed phase 1 dose escalation study investigated safety and tolerability of Dekavil (6 – 600µg/kg) in combination with MTX. The ongoing double-blind, placebo-controlled phase 2 study assesses the therapeutic activity of Dekavil plus MTX over MTX alone by measuring the mean change from baseline of DAS28-CRP. In total, 87 patients are randomized into two treatment groups (Dekavil 30 or 160 μg/kg plus MTX) and one placebo group (plus MTX).
Results: Phase 1: Up to 600µg/kg, an MTD was not reached. Neither SADRs nor SUSARs have been reported. One out of 35 treated patients (450 μg/kg cohort) experienced a DLT (G2 purpura) and a SAE (G2 dyspnea, not drug related). Mild injection site reactions were observed in 60% of the patients. Two cases of drug related anemia (G2-G3) were reported. All adverse reactions resolved completely. After 8 cycles of treatment, 57.7% of evaluable patients (15/26) revealed ACR and/or EULAR responses. Two patients benefited from ACR70 responses for more than 12 months.
Phase 2: As of April 2017, 22 patients have been enrolled and treated. No SUSARs, SAEs or deaths were reported.
Conclusion: The currently available data suggest that Dekavil is a safe, well tolerated and promising novel therapeutic for the treatments of RA. An interim analysis in the placebo-controlled phase 2 trial after 45 patients will allow for a more thorough understanding of the efficacy of the treatment