Dr. Noa Schwartz

Saphnelo Review  |  29.05.22

 

Research Inquiry

Review the recently approved drug Saphnelo (anifrolumab-fnia). This review will address indications, contra-indication, efficacy evidence, real-world reports, and additional relevant data.

 

Results

This report contains data and information as published by AstraZeneca, the regulatory authorities, and the scientific medical journals. As this drug was authorized in august 2021 there is still no real-world usage efficacy data that can provide new insights on top of the latest phase 3 clinical trial results published recently (2020) in the New England Journal Of Medicine. This report will provide summarized data regarding the topics mentioned in the research goals.

 

1 Introduction

On Aug. 2, 2021, AstraZeneca announced that FDA approved Saphnelo (anifrolumab-fnia), a type I interferon (type I IFN) receptor antagonist, for treating moderate to severe systemic lupus erythematosus (SLE) in adult patients who are receiving standard therapy. Anifrolumab-fnia is a human IgG1κ monoclonal antibody that binds to subunit 1 of the type I interferon receptor (IFNAR) with high specificity and affinity. This binding inhibits type I IFN signaling, thereby blocking the biologic activity of type I IFNs. 

 

Anifrolumab-fnia also induces the internalization of IFNAR1, thereby reducing the levels of cell surface IFNAR1 available for receptor assembly. Blockade of receptor-mediated type I IFN signaling inhibits IFN responsive gene expression as well as downstream inflammatory and immunological processes. Inhibition of type I IFN blocks plasma cell differentiation and normalizes peripheral T-cell subsets. 

 

Type I IFNs play a role in the pathogenesis of SLE. Approximately 60-80% of adult patients with active SLE express elevated levels of type I IFN inducible genes.

 

Indications

SAPHNELO is indicated for the treatment of adult patients with moderate to severe SLE, who are receiving standard therapy.

The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of SAPHNELO is not recommended in these situations.

 

Contraindications

SAPHNELO is contraindicated in patients with a history of anaphylaxis with  anifrolumab-fnia.

 

Due to anifrolumab’s side effect profile, clinicians should exercise caution in patients with an active infection or a history of herpes zoster.

Efficacy

 

Approval

The safety and efficacy of SAPHNELO were evaluated in three 52-week treatment period, multicenter, randomized, double-blind, placebo-controlled studies:

Trial 1 [MUSE; NCT01438489] published in 2018 in Lupus Science & Medicine]

Trial 2 [TULIP-1; NCT02446912] and Trial 3 [TULIP-2; NCT02446899] were published together in 2020 in The New England Journal Of Medicine

 

Patients were diagnosed with SLE according to the American College of Rheumatology classification criteria. All patients were ≥18 years of age and had moderate to severe disease, with an SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥6 points, organ level involvement based on the British Isles Lupus Assessment Group (BILAG) assessment, and a  Physician’s Global Assessment [PGA] score ≥1, despite receiving standard SLE therapy consisting of either one or any combination of oral corticosteroids (OCS), antimalarials and/or immunosuppressants at baseline. 

 

Patients continued to receive their existing SLE therapy at stable doses during the clinical trials, with the exception of OCS (prednisone or equivalent) where tapering was a component of the protocol. Patients who had severe active lupus nephritis and patients who had severe active central nervous system lupus were excluded. The use of other biologic agents and cyclophosphamide was not permitted during the trials; Patients received anifrolumab-fnia or placebo, administered by intravenous infusion, every 4 weeks. 

 

Efficacy of SAPHNELO was established based on the assessment of clinical response using the composite endpoints, the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) and the SLE Responder Index (SRI-4). 

BICLA response at Week 52, was defined as improvement in all organ domains with moderate or severe activity at baseline:

Reduction of all baseline BILAG A to B/C/D and baseline BILAG B to C/D, and no BILAG worsening in other organ systems, as defined by ≥1 new BILAG A or ≥2 new BILAG B;

No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of >0 points in SLEDAI-2K;

No worsening from baseline in patients’ lupus disease activity, where  worsening is defined by an increase ≥0.30 points on a 3-point PGA VAS;

No discontinuation of treatment;

No use of restricted medication beyond the protocol-allowed threshold. 

SRI-4 response was defined as meeting each of the following criteria at Week 52 compared with baseline:

Reduction from baseline of ≥4 points in the SLEDAI-2K

No new organ system was affected as defined by 1 or more BILAG A or 2 or more BILAG B items compared to baseline

No worsening from baseline in the patients’ lupus disease activity was defined by an increase ≥0.30 points on a 3-point PGA visual analog scale (VAS);

No discontinuation of treatment;

No use of restricted medication beyond the protocol-allowed threshold.

Overall results summary for the trials we:

 

 

A post hoc analysis, published in The Lancet Rheumatology Journal in February 2022 evaluated the efficacy of anifrolumab on organ domain-specific SLE disease activity. The analysis showed greater activity of anifrolumab in patients with musculoskeletal, mucocutaneous, and immunological systems involvement. Further information is available in the original article and in the response by prof. Martin Aringer published as well in The Lancet Rheumatology Journal in April 2022.




Real-world reporting

This section contains real-world reports and testimonials from patients as they were published in social media and patient forums:

 

Reports from patients on www.inspire.com:

User WolfSLE reports no substantial improvement in symptoms after 3 infusions of Saphnelo and no side effects.

User KristinMe described her response as “a miracle” after 4 infusions (“ didn’t notice the full effect until the 3rd infusion”). She feels energetic and mentions no side effects.

 

Reports on www.facebook.com

In a post from 26.5.22 in the Facebook group “Lupus Warriors” a user reports on “a lot of side effects” after the first Sphnelo infusion.

In a reply to the previously mentioned post, the user Cindy Martinez-Weaver mentioned she has been on Saphnelo for 4 months with no improvement.

User Lynett Marie posted on 3.5.22; “I saw significant improvements in 72 hours. My energy levels had improved; my joints were not as sore; the mouth sores healed. Since my first treatment in January, I have been receiving this medication every four weeks with my last treatment in April with no side effects.”

 

Repurposing

Anifrolumab is currently being investigated to extend indications.

 

A phase 2 study of anifrolumab for the treatment of patients with primary Sjögren’s Syndrome (NCT05383677).

A phase 3 Study of anifrolumab in patients with active proliferative lupus nephritis (NCT05138133).

A phase 2 study on anifrolumab in rheumatoid arthritis patients with a high IFN signature (NCT03435601)

 

References

Casey, Kerry A. “Type I interferon receptor blockade with anifrolumab corrects innate and adaptive immune perturbations of SLE.” Lupus Science & Medicine, vol. 5, no. 1, 2018, https://lupus.bmj.com/content/5/1/e000286.long.

 

Morand, Eric F F. “Trial of Anifrolumab in Active Systemic Lupus Erythematosus.” The New England Journal Of Medicine, vol. 383, 2020, pp. 211-221, https://www.nejm.org/doi/10.1056/NEJMoa1912196?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.

 

“Saphnelo (anifrolumab) approved in the US for moderate to severe systemic lupus erythematosus.” AstraZeneca, 2 August 2021, https://www.astrazeneca.com/media-centre/press-releases/2021/saphnelo-approved-in-the-us-for-sle.html. Accessed 27 May 2022.

 

“SAPHNELO Full Precribing Information.” sephanel, http://www.azpicentral.com/pi.html?product=saphnelo. Accessed 27 May 2022.

 

https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00317-9/fulltext

 

https://www.thelancet.com/pdfs/journals/lanrhe/PIIS2665-9913(21)00370-2.pdf#articleInformation