Tuesday, November 5, 2013

Mavrilimumab at the ACR 2013 Meeting in San Diego

Mavrilimumab is a human MAB for the treatment of rheumatoid arthritis. It targets the GM-CSF receptor-alpha. More at: http://en.wikipedia.org/wiki/Mavrilimumab
Usually we are talking about T and B cells in rheumatoid arthritis or maybe dendritic cells, but now neutrophils and macrophages come into focus. GM-CSF controls activation, differentiation, and survival of macrophages and neutrophils.
I've just been to an ACR review/update course here in Germany and the colleagues were very much in favour of this new drug.

There have been three studies on mavrilimumab at the ACR 2013 Meeting in San Diego.

G.-R. Burmester and colleagues presented the following study [Abstract #1733]: "Early and Sustained Improvement In Pain and Physical Function As Measured By Visual Analog Scale and Short Form-36 Physical Component Summary Score In Rheumatoid Arthritis Patients Treated With Mavrilimumab, An Investigational Anti-GM-CSFR-Alpha Monoclonal Antibody, In a Phase 2a Study." Conclusion: "Treatment with mavrilimumab 100mg resulted in an early onset and sustained improvement in pain relief and physical functioning as measured by VAS and SF-36 PCS, respectively, in moderate-severe RA patients. These findings are consistent with improvement in the disease activity (DAS28-CRP) and support further investigation of the blockade of the GM-CSF receptor with mavrilimumab in Phase 2b studies conducted in both DMARD-IR and TNF-IR patients."

W. White and colleagues presented the second study [Abstract #2377]: "Biomarkers Associated With Rheumatoid Arthritis Disease Activity Including Joint Damage Correlate With Changes In Clinical Response In Subjects Treated With Mavrilimumab At Doses Above 10 Mg." Conclusion: "Promising clinical safety and efficacy results of mavrilimumab support further clinical development at doses greater than 10 mg. Mechanistically, the drug suppressed both acute phase and inflammatory blood markers. Tracking of disease activity by MBDA showed a clear biomarker-based dose-response relationship. The association of MBSD decline with radiographic damage will be assessed in an on-going phase 2b study."
But there hasn't been any data on radiographic changes up to now.

P.C. Ryan and colleagues resented a study on monkeys [Abstract #2378]: "Safety Of Mavrilimumab In Cynomolgus Monkeys: Relevance Of Nonclinical Findings In Lung To Human Safety." Conclusion: "These results suggest that suppressing macrophage activity by targeting GM-CSF receptor alpha may be a novel approach with an acceptable safety profile for the treatment of RA."
Interestingly in "results" the results of a study published at the EULAR 2012 Meeting in Berlin has been quoted: "In EARTH,
mavrilimumab demonstrated good clinical activity with no clinically significant or persistent changes in the lung function tests performed. Likewise, the serum biomarkers of lung damage, SP-D and KL-6, showed no clinically significant changes following mavrilimumab treatment." The study at the EULAR 2012 had been by S. Spitz and colleagues [Abstract AB0576]; "Evaluation Of Surfactant Protein-D And Kl-6 As Potential Pulmonary Safety Biomarkers During Mavrilimumab Treatment".
It is like in a detective story - the inspector frowns if someone gives an alibi without being asked for it. Though as macrophages are involved the side effects on the lung should be monitored.

The recent data looks much better than what has been presented last year, but still we lack a study of longer duration with data on radiographic progression. And as the studies EARTH explorer 1 and 2 look at other dosages (also 150 mg) and test against golimumab for 24 weeks, results on radiographic progression still have a long way to come.

Summing it up: it looks better for mavrilimumab than a year ago, but still we don't know if there's going to be a new drug.


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