What are the benefits of this drug (results of trials used to assess efficacy)?

Table 1 below summarizes the efficacy results for individual trials 1, 2, and 3. Efficacy was assessed by comparing the proportion of patients who achieved BICLA response at Week 52 between SAPHNELO and placebo.

Table 1. Summary of Efficacy Results

Source: Adapted from FDA Review

Reported percentages for BICLA response rate are adjusted
Reported percentages of components are unadjusted
Abbreviations: BICLA, British Isles Lupus Assessment Group–based Composite Lupus Assessment; BILAG, British Isles Lupus Assessment Group; PGA, physician global assessment; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Figure 1 below shows the subgroup results, based on shrinkage analyses, for sex and race from the pooled results of Trials 1, 2, and 3. Most patients were younger than 65 years of age, therefore, the analysis by age was not performed.

Figure 1. Subgroup Analyses: Pooled Trials 1, 2, and 3

What are the possible side effects (results of trials used to assess safety)?

Table 2. Adverse Reactions Occurring in ≥2% of Patients on SAPHNELO 300 mg (Trials 1, 2, and 3) at 52 Weeks

Source: Adapted from FDA Review

All patients received standard therapy

^* Upper respiratory tract infections (including Upper respiratory tract infections, Nasopharyngitis, Pharyngitis)
^† Bronchitis (including Bronchitis, Bronchitis viral, Tracheobronchitis)
^ǂ Respiratory tract infection (including Respiratory tract infection, Respiratory tract infection viral, Respiratory tract infection bacterial)

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 3 below summarizes the occurrence of adverse events by race subgroups in the Phase 3 studies. Sex and age subgroups were not analyzed because the majority of patients were female and younger than 65 years of age.

Table 3. Subgroup Analysis of Treatment-Emergent Adverse Events by Race (Trials 2 and 3)

Source: Adapted from FDA Review

Abbreviations: TEAE, treatment-emergent adverse event

Who participated in the trials?

Table 4. Trial Demographics (Safety Population)

Source: Adapted from FDA Review

How were the trials designed?

There were three trials that provided data for SAPHNELO approval in SLE adult patients with moderate to severe disease despite receiving standard therapy. Patients were diagnosed with SLE according to the American College of Rheumatology (1982 revised) classification criteria. All patients were ≥18 years of age and had moderate to severe disease, with a SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥6 points, organ level involvement based on 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.

The safety and efficacy of SAPHNELO were evaluated in three 52-week treatment period, multicenter, randomized, double-blind, placebo-controlled studies (Trial 1/NCT01438489, Trial 2/NCT02446912 and Trial 3/NCT02446899). Patients continued to receive their existing SLE therapy at stable doses during the clinical trials, with the exception of 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 were not permitted during the trials.

Efficacy of SAPHNELO was established based on assessment of clinical response using the composite endpoints: the British Isles Lupus Assessment Group (BILAG)-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 per the following criteria:

• 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 visual analogue scale (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 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 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.

Trial 1 randomized 305 patients (1:1:1) who received SAPHNELO, 300 mg or 1000 mg, or placebo for up to 52 weeks. The primary endpoint was a combined assessment of the SRI-4 and the sustained reduction in daily prednisone (or prednisone equivalent) measured at Week 24, and a key secondary endpoint was BICLA at Week 52

Trials 2 and 3 were similar in design. Trial 2 randomized 457 patients who received SAPHNELO, 150 mg or 300 mg, or placebo (1:2:2). Trial 3 randomized 362 patients (1:1) who received SAPHNELO 300 mg or placebo. The primary endpoints were improvement in disease activity evaluated at 52 weeks, measured by SRI-4 in Trial 2 and BICLA in Trial 3.

Data from all three trials were used for safety assessment.