Sarilumab

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Sarilumab
Monoclonal antibody
Type Whole antibody
Source Human
Target IL-6R
Clinical data
Trade names Kevzara
AHFS/Drugs.com Multum Consumer Information
Routes of
administration
Subcutaneous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 80%
Metabolism likely proteases
Elimination half-life 21 days (steady-state, estimated)
Identifiers
CAS Number
PubChem SID
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6388H9918N1718O1998S44
Molar mass 144.13 kg/mol
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Sarilumab (trade name Kevzara) is a human monoclonal antibody against the interleukin-6 receptor.[1] Regeneron and Sanofi developed the drug for the treatment of rheumatoid arthritis (RA), for which it received US FDA approval on 22 May 2017 and European Medicines Agency approval on 23 June 2017.[2]

Development in ankylosing spondylitis has been suspended after the drug failed to show clinical benefit over methotrexate in a phase II trial.[3]

Medical uses[edit]

Sarilumab is used for the treatment of moderately to severely active rheumatoid arthritis in people who have not responded to, or did not tolerate, more conventional treatments. It can be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs).[4][5]

Contraindications[edit]

In Europe, sarilumab is contraindicated in people with active, severe infections.[4] While this is not listed as a contraindication under the US FDA approval, there is a boxed warning that recommends testing for hidden tuberculosis infection before treatment and monitoring for signs of an infection during therapy with sarilumab.[5]

Side effects[edit]

The MONARCH trial suggested a significantly higher incidence of neutropenia in patients receiving 200 mg sarilumab every 2 weeks, compared to patients being treated with adalimumab (13.6% vs 0.5%). However, infection rates were similar between both groups (28.8% vs 27.7%).[6]

Other common side effects that occurred in 1% to 10% of patients included thrombocytopenia (low platelet count), infections of the upper respiratory tract and the urinary tract, oral herpes, hyperlipidaemia, and reactions at the injection site.[4]

Clinical trials[edit]

Rheumatoid arthritis[edit]

On May 15, 2013, both companies announced that 2 new trials were starting (COMPARE and ASCERTAIN) and the first patients had already been enrolled.[7]

In June 2015, a phase 3 trial (with methotrexate) for RA reported meeting its three coprimary endpoints.[8]

In Nov 2015, the SARIL-RA-TARGET trial reported good results (meeting both its coprimary end points).[9]

In Nov 2016, the MONARCH phase III trial comparing sarilimab to adalimumab (an anti-TNF) found sarilumab superior at reducing the DAS28-ESR score in patients with RA after 24 weeks.[6]

History[edit]

In October 2016 the US FDA refused approval (for RA) due to GMP violations.[6] The drug was eventually approved by the FDA on 22 May 2017.

See also[edit]

References[edit]

  1. ^ "Statement On A Nonproprietary Name Adopted By The USAN Council: Sarilumab" (PDF). ama-assn.org. American Medical Association. (Subscription required (help)).
  2. ^ "Kevzara: Authorisation details". European Medicines Agency. Retrieved 28 September 2017.
  3. ^ "Sanofi and Regeneron Report Positive Phase 2b Trial Results with Sarilumab in Rheumatoid Arthritis". regeneron.com (Press release). Paris & Tarrytown, New York: Regeneron. July 12, 2011.
  4. ^ a b c "Kevzara: EPAR – Product Information" (PDF). European Medicines Agency. 2017-09-26.
  5. ^ a b Drugs.com: Sarilumab Monograph. Accessed 2017-11-29.
  6. ^ a b c Burmester GR, Lin Y, Patel R, van Adelsberg J, Mangan EK, Graham NM, et al. (May 2017). "Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial". Annals of the Rheumatic Diseases. 76 (5): 840–847. doi:10.1136/annrheumdis-2016-210310. PMC 5530335. PMID 27856432.
  7. ^ Sanofi and Regeneron Announce Patient Enrollment in Two Phase 3 Trials with Sarilumab in Rheumatoid Arthritis (RA). May 2013
  8. ^ Genovese MC, Fleischmann R, Kivitz AJ, Rell-Bakalarska M, Martincova R, Fiore S, et al. (June 2015). "Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study". Arthritis & Rheumatology. 67 (6): 1424–37. doi:10.1002/art.39093. PMID 25733246.
  9. ^ Walker T. "Sarilumab effective in broad range of RA patients: Study". Formulary Watch. Archived from the original on 21 November 2015.

Further reading[edit]