SAPHNELO FAQ

What is SAPHNELO and how does it work?
SAPHNELO is a first-in-class type I interferon (IFN) receptor antagonist, a human monoclonal antibody that binds to subunit 1 of the type I IFN receptor, blocking the activity of type I IFNs.1 Type I IFN are cytokines (cell signaling proteins) involved in a key pathway in lupus pathogenesis.2 Up to 80% of adult patients with moderate-to-severe systemic lupus erythematosus (SLE) have an elevated type I IFN gene signature, which can be associated with increased disease activity and severity.3-8

The approval by the US Food and Drug Administration (FDA) was based on efficacy and safety data from the SAPHNELO clinical development program, including two TULIP Phase III trials and the MUSE Phase II trial, in which treatment with SAPHNELO resulted in a reduction in overall disease activity across organ systems, including skin and joint, and sustained reduction in oral corticosteroid use, compared to placebo, with both groups receiving standard therapy. In addition, while not statistically significant, more patients in the clinical trials who were treated with SAPHNELO experienced less SLE flares over 52 weeks compared to placebo.1,9-11

How is SAPHNELO administered?
In the US, the recommended dose of SAPHNELO is 300 mg, administered as an intravenous infusion over a 30-minute period, every four weeks.1 SAPHNELO should be used as directed by a healthcare provider.

What makes SAPHNELO different from other lupus treatments?
As there are no head-to-head data, no direct comparisons can be made to other lupus treatments. However, SAPHNELO is a first-in-class SLE treatment that targets type I IFN signaling, which AstraZeneca believes offers a different way of treating this complex disease.1 Treatment with SAPHNELO resulted in a reduction in overall disease activity across organ systems, including skin and joint, and sustained reduction in oral corticosteroid use, compared to placebo, with both groups receiving standard therapy.1,9-11

In addition, while not statistically significant, more patients in the clinical trials who were treated with SAPHNELO experienced less SLE flares over 52 weeks compared to placebo.1,10

Who should take SAPHNELO? Will it work for everyone?
SAPHNELO is indicated in the US for the treatment of adult patients with moderate to severe SLE, who are receiving standard therapy.1 The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use is not recommended in these situations.1 SAPHNELO should not be used by patients with a history of anaphylaxis with the product.1

Importantly, data from TULIP-2, a Phase III trial, demonstrated a consistent response for patients treated with SAPHNELO irrespective of disease severity, baseline OCS use, age, gender, and race.1,10

Are patients with the highest interferon levels to benefit most from treatment with SAPHNELO?
SAPHNELO is indicated for the treatment of adult patients with moderate to severe SLE, who are receiving standard therapy.1 The approval of SAPHNELO is not limited by type I IFN levels.1

In SAPHNELO clinical trials, up to 80% of adult patients with moderate to severe SLE had an elevated IFN gene signature.12 Data from TULIP-2, a Phase III trial, showed that patients with both a high and low IFN gene signature had greater reductions in disease activity than placebo.13 There is no test for type I IFN levels or IFN gene signature required prior to starting treatment with SAPHNELO.1

Did you observe any efficacy differences in certain patient populations using SAPHNELO?
Overall, the treatment effect of SAPHNELO relative to placebo in TULIP-2, a Phase III trial, was consistent across subgroups, including race and ethnicity, disease severity, and baseline oral corticosteroid (OCS) use.1,10

Will there be any further clinical trials on SAPHNELO?
SAPHNELO continues to be evaluated in the TULIP SLE Phase III long-term extension trial.14 Additionally, subcutaneous anifrolumab is being evaluated in a Phase III trial in SLE.15

AstraZeneca will continue to explore SAPHNELO for other indications in which this first-in-class medicine could potentially benefit patients with an unmet medical need, including trials in lupus nephritis (LN) and cutaneous lupus erythematosus (CLE), myositis and pediatric patients with SLE.16,17

Are there any co-pay or patient assistance programs available for SAPHNELO?
AstraZeneca believes in supporting the many forms of access (i.e., medical coverage, resources, etc.) for all patients. A patient’s access and out-of-pocket costs are determined by their individual coverage. For eligible, commercially insured patients, AstraZeneca provides co-pay savings programs to help with costs at the pharmacy. And for patients without coverage and Medicare/Medicaid patients who need extra help paying for SAPHNELO, their healthcare provider’s office should contact Access 360 at [1-833-360-HELP] to determine what options may be available.

If there is a concern about a patient paying for SAPHNELO, their healthcare provider’s office should contact Access 360 at [1-833-360-HELP] to determine what options may be available.

What are the most common side effects of SAPHNELO?
The most common side effects of SAPHNELO include upper respiratory infections, bronchitis, infusion reactions, shingles and cough.1

IMPORTANT SAFETY INFORMATION
• Do not use SAPHNELO if you are allergic to anifrolumab-fnia or to any of the ingredients
• Before you receive SAPHNELO, tell your healthcare provider about all of your medical conditions, including if you:

• think you have an infection or have an infection that keeps coming back
• are scheduled to receive a vaccination or if you think you may need a vaccination. You should not receive live vaccines during treatment with SAPHNELO
• have or have had cancer
• are receiving other biologic medicines or monoclonal antibodies
• are pregnant or plan to become pregnant. It is not known if SAPHNELO will harm your unborn baby. Tell your healthcare provider if you are, might be, or plan to become pregnant during treatment with SAPHNELO
  • A pregnancy exposure registry monitors pregnancy outcomes in women exposed to SAPHNELO. You can find out more information about the registry by calling AstraZeneca at 1-877-693-9268
• are breastfeeding or plan to breastfeed. It is not known if SAPHNELO passes into your breast milk

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. SAPHNELO may affect the way other medicines work, and other medicines may affect how SAPHNELO works.

SAPHNELO may cause serious side effects, including:
• Serious infections: SAPHNELO can lower the ability of your immune system to fight infections. You may be at a higher risk of developing respiratory infections and shingles (herpes zoster) during treatment with SAPHNELO. Infections could be serious, leading to hospitalization or death
• Allergic (hypersensitivity) reactions, including anaphylaxis: Serious allergic reactions can happen during or after you get your SAPHNELO infusion. Tell your healthcare provider or get emergency help right away if you have any of the following symptoms of a serious allergic reaction:

• swelling of your face, mouth and tongue
• breathing problems
• fainting, dizziness
• feeling lightheaded (low blood pressure)
  • Cancer: SAPHNELO may reduce the activity of your immune system. Medicines that affect the immune system may increase your risk of certain cancers

The most common side effects of SAPHNELO include:

• Upper respiratory infections
• Bronchitis
• Infusion reactions
• Shingles (herpes zoster)
• Cough

Infusion reactions can happen at the time of the infusion or shortly after, symptoms may include headache, nausea, vomiting, feeling tired or weak (fatigue), and dizziness.

These are not all of the possible side effects of SAPHNELO. Call your healthcare provider for medical advice about side effects.

What is SAPHNELO?
SAPHNELO is a prescription medicine used to treat adults with moderate to severe systemic lupus erythematosus (SLE or lupus) who are receiving other lupus medicines.

It is not known if SAPHNELO is effective in patients with severe active lupus nephritis or severe active central nervous system lupus. It is not known if SAPHNELO is safe and effective in patients under 18 years of age.

Please see full Prescribing Information, including Patient Information.

References

1. SAPHNELO™ [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021.
2. Crow MK, Olferiev M, Kirou KA. Type I interferons in autoimmune disease. Annu Rev Pathol Mech Dis. 2019;14:369–93.
3. Hoffman, RW, Merrill, JT, et al. Gene Expression and Pharmacodynamic Changes in 1,760 Systemic Lupus Erythematosus Patients From Two Phase III Trials of BAFF Blockade With Tabalumab. Arthritis Rheumatol. 2017;69(3): 643–654. https://doi.org/10.1002/art.39950.
4. Becker, AM, Dao, KH, et al. SLE peripheral blood B cell, T cell and myeloid cell transcriptomes display unique profiles and each subset contributes to the interferon signature. PloS one. 2013;8(6), e67003. https://doi.org/10.1371/journal.pone.0067003.
5. Crow M. Type I interferon in the pathogenesis of lupus. J Immunol. 2014;192(12):5459-5468. doi:10.4049/jimmunol.1002795.
6. Lauwerys BR, Ducreux J, Houssiau FA. Type I interferon blockade in systemic lupus erythematosus: where do we stand? Rheumatology (Oxford). 2014;53(8):1369-1376.
7. Jefferies CA. Regulating IRFs in IFN driven disease. Front Immunol. 2019;10:325.
8. Mai L, Asaduzzaman A, Noamani B, et al. The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus. Arthritis Res Ther. 2021;23:29.
9. Furie R, et al. Anifrolumab, an Anti–Interferon‐α Receptor Monoclonal Antibody, in Moderate‐to‐Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017;69(2):376-386.
10. Morand E, et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020;382(3):211-221.
11. Furie R, et al. Anifrolumab: Type I Interferon Inhibition in Active Systemic Lupus Erythematosus in TULIP-1, a Phase 3, Randomized Controlled Trial. Lancet Rheumatol. 2019;1(4):e208-e219.
12. Tanaka Y, Tummala R. Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials. Modern Rheumatology. 2021;31(1):1-12.
13. Morand EF, Furie R, Tanaka Y, et al; TULIP-2 Trial Investigators. Trial of anifrolumab in active systemic lupus erythematosus. Supplementary appendix. N Engl J Med. 2020;382(3):211-221.
14. ClinicalTrials.gov. Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus (TULIP SLE LTE). NCT Identifier: NCT02794285. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02794285. Last accessed: July 2021.
15. ClinicalTrials.gov. Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus (Tulip SC). NCT Identifier: NCT04877691. Available at: https://clinicaltrials.gov/ct2/show/NCT04877691. Last accessed: July 2021.
16. AstraZeneca. H1 2021 Results. Available at: https://www.astrazeneca.com/content/dam/az/PDF/2021/h1-2021/H1_2021_results_presentation.pdf. Last accessed: July 2021.
17. U.S. Food and Drug Administration. SAPHNELO NDA Approval Letter. Available at: [insert link, once live on FDA website]. Last accessed: July 2021.