Last updated Feb. 6, 2023, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD
What is Saphnelo for Lupus?
Saphnelo (anifrolumab-fnia) is an injectable treatment approved to treat moderate to severe systemic lupus erythematosus (SLE), the most common form of lupus. It’s sold by AstraZeneca.Â
How does Saphnelo work?
Lupus is caused by the immune system launching an attack that damages the body’s own healthy tissues. Interferons, a group of pro-inflammatory signaling molecules, are known to play a role in this attack. In most SLE patients, interferon activity is upregulated.Â
Saphnelo is a monoclonal antibody that works by binding to the receptors immune cells use to detect interferons, blocking the pro-inflammatory signaling pathways that drive lupus and reducing disease activity.
Who can take Saphnelo?
Saphnelo was approved in the U.S. in 2021 to treat adults with moderate to severe SLE who are on standard background therapy, such as corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). It has also been approved in Canada, Japan, and the EU.
Who should not take Saphnelo?
Saphnelo has not been evaluated in patients with severe active kidney inflammation (lupus nephritis), or central nervous system involvement (severe active central nervous system lupus). It’s not recommended for use in these situations.Â
The medication should not be given to anyone with a known allergy history to its active ingredient and should not be used in combination with other biologic therapies.Â
How is Saphnelo administered?
Saphnelo is administered directly into the bloodstream (intravenously) via an infusion that lasts about 30 minutes. Infusions are given every every four weeks and the approved dose is 300 mg per infusion.Â
Saphnelo in clinical trials
MUSE trial
The Phase 2 MUSE trial (NCT01438489) Â included 305 adults with SLE with moderate to severe disease, defined as having a score of six or higher on the SLE Disease Activity Index 2000 (SLEDAI-2K), despite receiving standard therapy. Nearly all were female (93%) and almost half (42%) were white. Participants were a mean age of 40.
Patients were randomly assigned to receive Saphnelo at one of two doses (300 or 1,000 mg) or a placebo, every four weeks for about a year.Â
The study’s main goal was to assess the proportion of patients considered respondents on the SLE Responder Index (SRI-4). A response on the SRI-4 means disease severity has decreased with no evidence of new disease activity. Another measure called the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) was also assessed. To be considered a responder on BICLA, patients had to show improvements in every organ that had moderate or severe disease activity at the study’s start and show no signs of disease worsening in other measures.Â
After a year, the SRI-4 response rate was significantly higher — by 24% — for those on 300 mg of Saphnelo compared with those given a placebo (62.8% vs. 38.8%). The BICLA response rate also was higher, by more than 28% in Saphnelo-treated patients (54.6% vs. 25.8%).
TULIP trials
The Phase 3 clinical trials TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) tested the safety and effectiveness of Saphnelo against a placebo in more than 800 people with moderate to severe SLE. Demographics were generally comparable to the MUSE trial, although the proportion of white patients was somewhat higher (71% in TULIP-1, 60% in TULIP-2), while there were fewer Hispanic patients (19% in TULIP-1, and 30% in TULIP-2).Â
In TULIP-1, 457 patients were randomly assigned to receive Saphnelo at a dose of 150 or 300 mg, or a placebo. In TULIP-2, 362 patients were randomized to be given 300 mg of Saphnelo or a placebo. Both trials lasted a year and assessed the effect of treatment on SRI-4 and BICLA response rates.Â
In both trials, the BICLA response rate was significantly higher for those on 300 mg of Saphnelo compared to a placebo (47.1% vs. 30.2% in TULIP-1; 47.8% vs. 31.5% in TULIP-2). The SRI-4 response rate was significantly higher for 300 mg Saphnelo than a placebo in TULIP-2 (55.5% vs. 37.3%), while in TULIP-1 the SRI-4 response rate was higher for Saphnelo-treated patients, but the difference did not reach statistical significance (49% vs. 43%).
Ongoing trials
AstraZeneca is sponsoring a Phase 3 clinical trial (NCT04931563) to assess the safety and effectiveness of Saphnelo against a placebo in Asian patients with active SLE. The study is ongoing at several locations in China, Korea, Hong Kong, Thailand, Taiwan, and the Philippines.Â
The company is also conducting multiple studies to collect data on Saphnelo’s efficacy in real-world clinical practice, including an observational study called ASTER (NCT05637112) and a post-marketing surveillance study in Japan (NCT05141201).Â
Another Phase 3 trial called IRIS (NCT05138133) is evaluating the safety and efficacy of Saphnelo against a placebo in people with active proliferative lupus nephritis. It intends to enroll 360 participants at locations around the globe and its main goal is to evaluate the proportion of patients whose kidney function is within or close to normal limits after one year. Â
AstraZeneca is also developing a formulation of Saphnelo designed to be administered subcutaneously (under-the-skin). An ongoing Phase 1 study (NCT05339100) is comparing the pharmacological properties of the therapy in healthy volunteers when administered with an autoinjector or an accessorized pre-filled syringe.
A Phase 3 trial (NCT04877691) is comparing the effectiveness of subcutaneous Saphnelo against a placebo in people with moderate to severe SLE. This study aims to enroll about 360 patients and its main goal is to compare BICLA response rates after one year.
Common side effects of Saphnelo
The most common side effects of Saphnelo include:Â
- the common cold (nasopharyngitis)Â
- upper respiratory tract infections
- bronchitis
- infusion related reactions, most commonly headache, nausea, vomiting, fatigue, and dizziness
- shingles (herpes zoster)
- cough
Infections and vaccinations
Because Saphnelo reduces the activity of the immune system, it may increase the risk of infections, including respiratory infections and herpes zoster. Serious and fatal infections have occurred in patients who were on the therapy.Â
Patients with an active infection should not be started on Saphnelo and if an infection develops on the therapy, pausing treatment should be considered. In patients with chronic infections, the benefits and risks of Saphnelo should be carefully considered.Â
Patients on Saphnelo should not be given vaccines that contain a live virus.
Allergic reactions
Serious allergic reactions to Saphnelo have been reported, including anaphylaxis — a sudden onset of severe symptoms like swelling, lightheadedness, dizziness, and breathing problems, which can be life-threatening. If an allergic reaction occurs, treatment with Saphnelo should be stopped immediately and appropriate therapy to manage the reaction should be given as soon as possible.Â
Potential cancer risk
In addition to fighting off viruses, the immune system helps destroy rogue cells that have the potential to become cancerous. As such, many medicines that suppress the immune system can increase cancer risk, though it’s not yet known whether Saphnelo is associated with an increased cancer risk. In patients with cancer or in those who are at an increased risk of developing it, the potential benefits and risks of Saphnelo should be carefully weighed.Â
Use in pregnancy and breastfeeding
Saphnelo’s safety in pregnancy has not been thoroughly studied in humans. Experiments done in nonhuman primates have not shown any substantial toxicity for the developing fetus or the pregnant mother when Saphnelo is administered during pregnancy. A registry is collecting data on women who are exposed to Saphnelo during pregnancy. It can be contacted by calling AstraZeneca at 1-877-693-9268.
There is currently no data about whether Saphnelo passes to human breast milk or whether using it while breastfeeding could pose any risks to the infant. The potential risks should be weighed against the benefits of treatment when deciding whether to use Saphnelo during pregnancy or breastfeeding.
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