Sarilumab

Last updated
Sarilumab
Monoclonal antibody
Type Whole antibody
Source Human
Target IL-6R
Clinical data
Trade names Kevzara
AHFS/Drugs.com Monograph
MedlinePlus a617032
License data
Routes of
administration
Subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 80%
Metabolism likely proteases
Elimination half-life 21 days (steady-state, estimated)
Identifiers
CAS Number
  • 1189541-98-7 X mark.svgN
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6388H9918N1718O1998S44
Molar mass 144164.28 g·mol−1
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Sarilumab, sold under the brand name Kevzara, is a human monoclonal antibody medication against the interleukin-6 receptor. [1] Regeneron Pharmaceuticals 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]

Contents

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

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. [4] It can be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs). [5] [6]

Contraindications

In the European Union, 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 III trial (with methotrexate) for RA reported meeting its three coprimary endpoints. [9]

In November 2015, the SARIL-RA-TARGET trial reported good results (meeting both its coprimary end points). [10]

In November 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]

In July 2019, a multi-center trial was launched to study 'Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis.' [11]

History

In October 2016, the U.S. Food and Drug Administration (FDA) refused approval for marketing as a treatment for rheumatoid arthritis due to good manufacturing practice (GMP) violations. [7] The drug was eventually approved by the FDA on 22 May 2017.

Research

COVID-19

A study of 420 patients was halted in September 2020, due to lack of demonstrated effectiveness in treating COVID-19 symptoms. [12]

On January 7, 2021, following a REMAP-CAP trial, Tocilizumab and Sarilumab were added to the UK recommended list for COVID-19 treatment, the number needed to treat is 12, meaning for every 12 intensive care unit patients treated 1 additional person survives compared to treatment as normal, also speeding up patients' recovery and reducing the length of time that critically-ill patients need to spend in intensive care by about a week [13]

Related Research Articles

Rheumatology is a branch of medicine devoted to the diagnosis and therapy of rheumatic diseases. Physicians who have undergone formal training in rheumatology are called rheumatologists. Rheumatologists deal mainly with immune-mediated disorders of the musculoskeletal system, soft tissues, autoimmune diseases, vasculitides, and inherited connective tissue disorders.

Infliximab

Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals.

Adalimumab Pharmaceutical drug

Adalimumab, is a disease-modifying antirheumatic drug and monoclonal antibody that works by inactivating tumor necrosis factor-alpha (TNFα). It is sold under the brand name Humira, among others. It is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis, hidradenitis suppurativa, uveitis, and juvenile idiopathic arthritis. Use is generally only recommended in people who have not responded to other treatments. It is administered by injection under the skin.

Anakinra

Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein. It is marketed by Swedish Orphan Biovitrum. Anakinra is administered by subcutaneous injection.

Leflunomide

Leflunomide, sold under the brand name Arava among others, is an immunosuppressive disease-modifying antirheumatic drug (DMARD), used in active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.

Regeneron Pharmaceuticals American biotechnology company

Regeneron Pharmaceuticals, Inc. is an American biotechnology company headquartered in Westchester County, New York, about 25 miles north of Midtown Manhattan. The company was founded in 1988. Originally focused on neurotrophic factors and their regenerative capabilities, giving rise to its name, the company then branched out into the study of both cytokine and tyrosine kinase receptors.

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

Biological therapy for inflammatory bowel disease

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

Belimumab

Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States, Canada, and the European Union to treat systemic lupus erythematosus (SLE).

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis, a severe form of arthritis in children. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

Anti-interleukin-6 agents are a class of therapeutics. Interleukin 6 is a cytokine relevant to many inflammatory diseases and many cancers. Hence, anti-IL6 agents have been sought. In rheumatoid arthritis they can help patients unresponsive to TNF inhibitors.

Tofacitinib medication

Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.

Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony-stimulating factor receptor (GM-CSF-R).

Namilumab is a human monoclonal antibody that targets granulocyte macrophage-colony stimulating factor (GM-CSF)/colony stimulating factor 2 (CSF2) and is currently being researched for application in rheumatoid arthritis (RA) and psoriatic arthritis. Clinical trials investigating the therapeutic utility of Namilumab have include phase I and phase II clinical trials to establish the safety, tolerability and preliminary therapeutic utility of the antibody in plaque psoriasis and rheumatoid arthritis.

Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. It is a human monoclonal antibody that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety.

Baricitinib

Baricitinib, sold under the brand name Olumiant among others, is a drug for the treatment of rheumatoid arthritis (RA) in adults whose disease was not well controlled by tumor necrosis factor (TNF) inhibitors. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2. The drug is approved for medical use in the European Union and in the United States.An important side effect of JAK inhibitors is serious bacterial, mycobacterial, fungal and viral infections.

Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody used for allergic diseases such as eczema, asthma and nasal polyps which result in chronic sinusitis.

Filgotinib

Filgotinib, sold under the brand name Jyseleca, is a medication used for the treatment of rheumatoid arthritis (RA). It was developed by the Belgian-Dutch biotech company Galapagos NV.

Upadacitinib Chemical compound (medication)

Upadacitinib, sold under the brand name Rinvoq, is a Janus kinase (JAK) inhibitor medication for the treatment of moderately to severely active rheumatoid arthritis in adults where methotrexate did not work well or could not be tolerated. It was approved for medical use in the United States and in the European Union in 2019, and was developed by the biotech company AbbVie.

Antiarthritics

An antiarthritic is any member of the group of drugs used to relieve or prevent arthritic symptoms, such as joint pain and joint stiffness. Depending on the antiarthritic drug class, it can be responsible for managing pain, reducing inflammation and/or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the type/nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.

References

  1. "Statement On A Nonproprietary Name Adopted By The USAN Council: Sarilumab" (PDF). ama-assn.org. American Medical Association.
  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. Boyce EG, Rogan EL, Vyas D, Prasad N, Mai Y (Feb 2018). "Sarilumab: Review of a Second IL-6 Receptor Antagonist Indicated for the Treatment of Rheumatoid Arthritis". Annals of Pharmacotherapy. 52 (8): 780–791. doi:10.1177/1060028018761599. PMID   29482351. S2CID   3580054.
  5. 1 2 3 "Kevzara: EPAR – Product Information" (PDF). European Medicines Agency. 2017-09-26.
  6. 1 2 Drugs.com: Sarilumab Monograph . Accessed 2017-11-29.
  7. 1 2 3 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.
  8. Sanofi and Regeneron Announce Patient Enrollment in Two Phase 3 Trials with Sarilumab in Rheumatoid Arthritis (RA). May 2013
  9. 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.
  10. Walker T. "Sarilumab effective in broad range of RA patients: Study". Formulary Watch. Archived from the original on 21 November 2015.
  11. "More Information". Sarcoidosis Program. Retrieved 2019-08-09.
  12. Sanofi halts tests of arthritis drug for use as a COVID-19 treatment
  13. Roberts, Michelle (2021-01-07). "Two more life-saving Covid drugs discovered". BBC News. Retrieved 2021-01-07.

Further reading