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Mavrilimumab

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Mavrilimumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetGM-CSF receptor alpha chain
Clinical data
ATC code
  • none
Identifiers
CAS Number
IUPHAR/BPS
ChemSpider
  • none
UNII
Chemical and physical data
FormulaC6706H10438N1762O2104S54
Molar mass143.2 kg/mol g·mol−1
 ☒NcheckY (what is this?)  (verify)

Mavrilimumab is a human monoclonal antibody designed for the treatment of rheumatoid arthritis.[1] It is an inhibitor of human granulocyte macrophage colony-stimulating factor receptor (GM-CSF-R).[2]

Mavrilimumab was discovered as CAM-3001 by Cambridge Antibody Technology and is being developed by MedImmune, Inc.[3]

It has so far shown positive results in phase 1[2] and phase 2a clinical trials.[4] A phase 2a trial which studied mavrilimumab doses of up to 100 mg, reported that 55.7% of subjects met the primary endpoint of "a ≥1.2 decrease from baseline in Disease Activity Score (DAS28-CRP) at week 12" (vs. only 34.7% of placebo subjects).[4] Two further clinical studies are reported to be underway in rheumatoid arthritis patients to investigate these effects further.[5]

Preliminary results, from a phase IIb study investigating doses of 30, 100 and 150 mg mavrilimumab over 24 weeks, were presented at a rheumatology conference in Rome, in August 2015. At week 24, 40.15% of patients in the top dose group achieved an ACR50 response compared to 3.7% in the placebo group. Rates of remission and low disease activity were reported to be significantly higher in the 150-mg group.[6] Patients who completed this and a second US clinical study were enrolled into an open-label extension study to evaluate the longer term efficacy and safety of mavrilumumab for up to 74 weeks of treatment, presented at a rheumatology conference in San Francisco in November 2015. The authors concluded that 150 mg mavrilimumab was optimal for patients who had prior inadequate response to non-biological DMARDs compared to a dose of 100 mg every other week which had produced positive results in patients still receiving methotrexate.[7]

References

  1. ^ "Statement On A Nonproprietary Name Adopted By The USAN Council: Mavrilimumab" (PDF). American Medical Association.
  2. ^ a b Gerd R Burmester, Eugen Feist, Matthew A Sleeman, Bing Wang, Barbara White and Fabio Magrini (1 September 2011). "Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-α, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study". Ann. Rheum. Dis. 70 (9): 1542–1549. doi:10.1136/ard.2010.146225. PMC 3147227.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ http://www.ama-assn.org/resources/doc/usan/mavrilimumab.pdf
  4. ^ a b Gerd R Burmester; Michael E Weinblatt; Iain B McInnes; Duncan Porter; Olga Barbarash; Mykola Vatutin; Istvan Szombati; Ehsanollah Esfandiari; Matthew A Sleeman; Christopher D Kane; Guy Cavet; Bing Wang; Alex Godwood; Fabio Magrini; the EARTH Study Group. "Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis". Ann Rheum Dis. 72 (9): 1445–1452. doi:10.1136/annrheumdis-2012-202450. PMC 3756523. {{cite journal}}: Unknown parameter |last-author-amp= ignored (|name-list-style= suggested) (help)
  5. ^ Manuela Di Franco; Maria Chiara Gerardi; Bruno Lucchino; Fabrizio Conti (12 March 2014). "Mavrilimumab: an evidence based review of its potential in the treatment of rheumatoid arthritis". Core Evidence. 9: 41–48. doi:10.2147/CE.S39770. PMC 3958547. {{cite journal}}: Unknown parameter |last-author-amp= ignored (|name-list-style= suggested) (help)CS1 maint: unflagged free DOI (link)
  6. ^ Nancy Walsh (15 June 2015). "Targeting GM-CSF Succeeds in RA - Primary endpoints met in phase IIb study of mavrilimumab". MedPageToday. Retrieved 24 February 2016.
  7. ^ G Burmester, IB McInnes, JM Kremer, P Miranda, J Vencovský, A Godwood, M Albulescu, D Close and Michael Weinblatt (29 September 2015). "Abstract Number 3111: Long-term Safety and Efficacy of Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor-α (GM–CSFR-α) Monoclonal Antibody, in Patients with Rheumatoid Arthritis (RA) [abstract]". Arthritis Rheumatol. 67 (suppl 10). American College of Rheumatology.{{cite journal}}: CS1 maint: multiple names: authors list (link)