dm+d

Unassigned

New Medicines

SaphneloSystemic lupus erythematosus (SLE)

Information

Saphnelo
New molecular entity
AstraZeneca
MedImmune

Development and Regulatory status

PIII
Pre-registration (Filed)
Launched
Aug 21Launched in the US [20]
Aug 21Approved in US [19].
Dec 20Has also been filed in the US [16].
Nov 20Regulatory decisions from the EMA and FDA are expected H2 2021 [18].
Nov 20Filed in EU via centralised procedure [15].
Dec 19EU and US filing expected for H2 2020. Fast Track Designation in US [13].
May 19EU & US filings planned for 2020 [10].
Dec 17Still on track for filing in 2019 according to AZ pipeline updated 9/11/17 [5]
Dec 16EU &US filings still planned for 2019 [4]
Nov 15US FDA recently assigned anifrolumab Fast Track designation [1].
Nov 15A PI subcutaneous administration study is anticipated to begin in H2 2015 [1].
Sep 15EU &US filings planned for 2019 [3].
Jul 15PIII programme including the TULIP study begins [1].

Category

First-in-class fully human monoclonal antibody that binds to subunit 1 of the Type I IFN receptor, inhibiting the activity of all Type I IFNs including IFN-α, IFN-β and IFN-ω.
The UK prevalence of SLE is 25-28 per 100,000 population; over 90% develop arthralgia and myalgia.
Systemic lupus erythematosus (SLE)
Intravenous

Further information

Yes

Trial or other data

Mar 21PII 3yr extension study (NCT01753193, n=218) found the rate and pattern of adverse effects were consistent with those reported at 1yr and few discontinued owing to adverse effects. Clinical improvements at 1yr were reported to be sustained at 3yrs [17].
Dec 19PIII TULIP SLE2 (NCT02446899; n=362) is published in the NEJM; it found monthly administration of anifrolumab (300mg IV), a monoclonal antibody to type I interferon receptor subunit 1, resulted in higher response rate at week 52 than placebo (47.8 vs. 31.5%; p=0.001), in contrast to previous trial with different primary end point [14].
Nov 19Outcome data from PIII TULIP 2 trial (n=365) available in which pts received either i.v. anifrolumab 9300mg) or placebo every month. The primary endpoint (as measured by the British Isles Lupus Assessment Group-based Composite Lupus Assessment [BICLA] composite measure) at week 52 was acheived by 47.8% of pts receiving anifrolumab vs. 31.5% on placebo (reported as statistically significant). In addition, 51.5% of anifrolumab pts on oral steroids (OCS) showed a sustained reduction in OCS use vs. 30.2% with placebo and 49% on anifrolumab showed improved skin symptoms at week 12 vs. 25% on placebo.[12]
Aug 19AstraZeneca announce PIII TULIP 2 trial meets primary endpoint of statistically-significant and clinically-meaningful reduction in disease activity measured using the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) at week 52 [11].
Aug 18Phase III trial results from the TULIP 1 study in adult patients with moderate-to-severe systemic lupus erythematosus (SLE) found that the primary endpoint of a statistically-significant reduction in disease activity in patients with SLE as measured by the SLE Responder Index 4 (SRI4) at 12 months was not met [8].
Feb 18Results expected from TULIP SLE2 in H2 19 [9].
Dec 17Data expected H2 18 from TULIP SLE1 (NCT02446912) and TULIP SLE2 (NCT02446899) [7].
Dec 17NCT02547922 due to complete May 2019 [6]
Nov 15PIII TULIP-LN1 (NCT02547922) will recruit 150 pts from 71 sites in the US, EU (including UK) and other countries worldwide. Primary outcome data collection should complete Apr 18 [2].
Nov 15The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) programme includes two PIII clinical trials that will evaluate the efficacy and safety of anifrolumab versus placebo in patients with moderately to severely active, autoantibody-positive SLE, while receiving standard of care treatment. The programme will assess the effect of anifrolumab in reducing disease activity (as measured by the SRI), decreasing use of OCS, improving skin manifestations (as measured by CLASI) and reducing flares [1].
Nov 15AstraZeneca & Medimmune announce that a PII trial met its primary endpoint of difference in percentage of patients who achieved response as measured by the SLE Responder Index 4 (SRI4) at day 169, along with a sustained reduction of oral corticosteroid (OCS) use between day 85 and day 169. Responses occurred for 34.4% of patients receiving anifrolumab 300mg IV and for 28.8% of patients receiving anifrolumab 1,000mg IV every four weeks versus 17.6% of patients receiving placebo. The trial also met both secondary efficacy endpoints measuring responses at day 365, with even greater effect. Over 50 percent (51.5) of patients receiving anifrolumab 300mg and 38.5% of patients receiving anifrolumab 1,000mg achieved SRI4 response at day 365 with sustained reduction of OCS, compared with 25.5% of patients receiving placebo. The trial also met its other secondary endpoint of a reduction of OCS use to ≤7.5 mg/day by day 365 in those patients taking ≥10 mg/day of OCS at baseline [1].

Evidence based evaluations