Dekavil at the 2017 EULAR Annual Meeting in Madrid

Dekavil (F8-IL10) is a fully human immunocytokine, composed of the antibody fragment F8 fused to the anti-inflammatory cytokine interleukin-10 (IL-10). I’ve come across dekavil for the first during the 2012 EULAR Annual Meeting in Berlin [1]. I’ve been quite mad after the 2013 EULAR Annual Meeting in Madrid [2]: “Please promise to publish more than promising data at the ACR 2013 at the next ACR meeting.”

M. Galeazzi and colleagues published a phase 2 study [3] titled: “SAFETY, TOLERABILITY AND INITIAL SIGNS OF EFFICACY OF THE FULLY HUMAN IMMUNOCYTOKINE DEKAVIL (F8IL10): A NOVEL THERAPEUTIC APPROACH FOR RHEUMATOID ARTHRITIS”. The abstract is difficult to read as it also looks at data from a phase 1b study. “As of January 2017, 22 out of 87 patients have been treated in the phase 2 clinical study and neither SUSAR [Suspected Unexpected Serious Adverse Reaction] nor treatment-related deaths were recorded.” Conclusions: “The currently available data suggest that Dekavil is a safe and promising novel therapeutic for the treatments of RA.” I don’t see such a conclusion. And yeah, there we are again – promising.

Adisinsight reports termination of a phase 1 trial in Inflammation (in volunteers) in the US in2016 and of a phase 2 clinical trials in rheumatoid arthritis in Italy in 2014 [4].

On the other hand this study “A Randomized, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Efficacy of F8IL10 (Dekavil) in Patients With Active RA Receiving MTX” is marked as “is currently recruiting participants” in Clinical Trials [5].

It’s hard to share the enthusiasm of the authors. The idea of getting IL-10 to where inflammation is raging is wonderful. I don’t want to sound like a merchant of doom, but I have my doubts about dekavil.

Links and References:

[1] http://rheumatologe.blogspot.de/2012/07/dekavil-at-eular-2012.html

[2] http://rheumatologe.blogspot.de/2013/06/dekavil-at-eular-2013.html

[3] DOI: 10.1136/annrheumdis-2015-eular.3889

[4] http://adisinsight.springer.com/drugs/800032511

[5] https://clinicaltrials.gov/ct2/show/NCT02270632

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Dekavil at the EULAR 2013

I’ve seen a poster on dekavil at the EULAR 2013 meeting. Let’s return to the ACR 2012 meeting for a moment. I’d written:
“Maybe we have to wait for a couple of years to evaluate dekavil. If the results are as good as shown in the abstract, then it could develop into a block buster. Philogen S.p.A. hasn’t rushed yet to large scale international multicenter studies and I interpret this as a hint, that the potential of this drug isn’t as high as the study of M. Galeazzi wants us to believe.”

M. Galeazzi and colleagues presented [SAT0108]: Dekavil (F8-IL10): a novel anti-inflammatory immunocytokine for the treatment of rheumathoid arthritis”. Conclusions: “The promising safety data regarding the clinical use of F8-IL10, together with preliminary positive signs of activity, suggest that the targeted delivery of IL10 to the site of inflammation may be beneficial to patients with RA. These results also warrant future developments of the product in randomized clinical trials. An update of clinical data will be presented.”

That’s not so different from the text presented at the ACR 2012: “The promising safety data regarding the clinical use of F8-IL10, together with preliminary positive signs of activity may be favored by the targeted delivery of IL10 to the site of inflammation. These results also warrant future developments of the product in randomized clinical trials, which are currently in planning. An update of clinical data will be presented at the ACR meeting.”
Please promise to publish more than promising data at the ACR 2013 at the next ACR meeting.

Links:

http://rheumatologe.blogspot.de/2012/12/dekavil-at-acr-2012-in-washington.html
http://rheumatologe.blogspot.de/2012/07/dekavil-at-eular-2012.html

Dekavil at the ACR 2012 in Washington

Dekavil - fibronectin-A-chain connected to IL-10 or as it is said in the abstract below: “F8-IL10 is a fusion protein in which the cytokine is fused with the antibody F8 specific to the alternatively-spliced EDA domain of fibronectin, a marker of angiogenesis.” Link to my blog post on the drug at the EULAR 2012: http://rheumatologe.blogspot.de/2012/07/dekavil-at-eular-2012.html  

The poster says it’s dekavil, but the name isn’t mentioned in the abstract! M. Galeazzi and colleagues presented: "A Phase Ib Clinical Trial with F8-IL10, an Anti-Inflammatory Immunocytokine for the Treatment of Rheumatoid Arthritis (RA), Used in Combination with Methotrexate (MTX)" (AbstractNo.1291). In this ongoing dose finding study, results are only clear for the low dosages (6 mg and 15 mg/kg body weight). On the poster achievements of ACR50 in 2 patients and ACR70 in 1 patient are shown. Maybe the drug is ao powerful, but maybe it’s simply an effect due to an unblinded study design. Conclusion: “These results also warrant future developments of the product in randomized clinical trials, which are currently in planning.”

Maybe we have to wait for a couple of years to evaluate dekavil. If the results are as good as shown in the abstract, then it could develop into a block buster. Philogen S.p.A. hasn’t rushed yet to large scale international multicenter studies and I interpret this as a hint, that the potential of this drug isn’t as high as the study of M. Galeazzi wants us to believe.

Dekavil at the EULAR 2012

Dekavil inhibits the progression of collagen-induced arthritis, which is a mouse model for rheumatoid arthritis. You can look at the whole article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787264/  
This immunocytokine is a combination of the F8 antibody (specific to a part of fibronectin) and interleukin-10 (IL-10). Predominantly monocytes produce IL-10, which effects immunoregulation and inflammation.
At the EULAR 2012 Meeting in Berlin Dekavil has been introduced in one study. M. Galeazzi and colleagues presented a phase Ib clinical trial with dekavil in combination with methotrexate. The study shows preliminary results, as it is still ongoing. Dekavil has been tolerated well. The authors report a surprising result of reaching ACR50 after 8 weeks.


[FRI0194] A PHASE IB CLINICAL TRIAL WITH DEKAVIL (F8-IL10), AN ANTI-INFLAMMATORY IMMUNOCYTOKINE FOR THE TREATMENT OF RHEUMATOID ARTHRITIS, USED IN COMBINATION WITH METHOTREXATE
M. Galeazzi1, C. Baldi1, K. Schwager2, D. Neri3, L. Giovannoni4, E. Selvi1. 1Rheumatology Unit, University of Siena, Siena, Italy; 2Philochem AG, Otelfingen; 3Swiss Federal Institute of Technology, Zurich, Switzerland; 4Clinical Research Unit, Philogen S.p.a., Sovicille, Italy
Conclusions: The promising safety data about the clinical use of DEKAVIL, together with emerging signs of potent activity in heavily pre-treated patients, warrants future developments of the product in randomized clinical trials, which are currently in planning. An update of clinical data will be presented at the EULAR meeting.


Preliminary results of an ongoing phase Ib study. We shouldn’t get too excited, but there is a need of further clinical trials. Other competitors have started with less!