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 |
|
| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C6388H9918N1718O1998S44 |
| Molar mass | 144.13 kg/mol g·mol−1 |
  (what is this?) (verify) | |
Sarilumab (trade name Kevzara) is a human monoclonal antibody against the interleukin-6 receptor.[2] 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.[3]
Development in ankylosing spondylitis has been suspended after the drug failed to show clinical benefit over methotrexate in a phase II trial.[4]
Medical uses
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).[5][6]
Contraindications
In Europe, sarilumab is contraindicated in people with active, severe infections.[5] 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.[6]
Side effects
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%).[7]
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.[5]
Clinical trials
Rheumatoid arthritis
On May 15, 2013, both companies announced that 2 new trials were starting (COMPARE and ASCERTAIN) and the first patients had already been enrolled.[8]
In June 2015, a phase 3 trial (with methotrexate) for RA reported meeting its three coprimary endpoints.[9]
In Nov 2015, the SARIL-RA-TARGET trial reported good results (meeting both its coprimary end points).[10]
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.[7]
History
In October 2016 the US FDA refused approval (for RA) due to GMP violations.[7] The drug was eventually approved by the FDA on 22 May 2017.
See also
- Anti-IL-6 anti-inflammatories
References
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ "Statement On A Nonproprietary Name Adopted By The USAN Council: Sarilumab" (PDF). ama-assn.org. American Medical Association.
{{cite web}}: Unknown parameter|subscription=ignored (|url-access=suggested) (help) - ^ "Kevzara: Authorisation details". European Medicines Agency. Retrieved 28 September 2017.
- ^ "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.
- ^ a b c "Kevzara: EPAR – Product Information" (PDF). European Medicines Agency. 2017-09-26.
- ^ a b Drugs.com: Sarilumab Monograph. Accessed 2017-11-29.
- ^ a b c Burmester, Gerd R; Lin, Yong; Patel, Rahul; et al. (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 – via bmj.com.
- ^ Sanofi and Regeneron Announce Patient Enrollment in Two Phase 3 Trials with Sarilumab in Rheumatoid Arthritis (RA). May 2013
- ^ "Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study". Arthritis Rheumatol. 67 (6): 1424–37. 2015. doi:10.1002/art.39093. PMID 25733246.
- ^ Sarilumab effective in broad range of RA patients: Study