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  5. Drug Trials Snapshot: LUPKYNIS
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Drug Trials Snapshot: LUPKYNIS

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the LUPKYNIS Package Insert for complete information.

LUPKYNIS (voclosporin)
(loop kye’ nis)
Aurinia Pharmaceuticals
Approval date: January 22, 2021

DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

LUPKYNIS is a drug used to treat patients with active lupus nephritis.

Lupus nephritis (LN) is an inflammation of the kidneys that is caused by systemic lupus erythematous (SLE) - a chronic, autoimmune disease.

How is this drug used?

LUPKYNIS is a capsule that is taken twice daily by mouth in combination with two other drugs (mycophenolate mofetil and corticosteroid).

What are the benefits of this drug?

In the clinical trial, a greater proportion of patients who received LUPKYNIS for one year, achieved a reduction in the kidney inflammation in comparison to patients who received placebo.

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

The table below summarizes the efficacy results for Trial 1. The primary endpoint was complete renal response at Week 52.

Table 1. Complete Renal Response at Week 52 in Trial 1.

 

LUPKYNIS
(N=179)

Placebo
(N=178)

Odds Ratio
 

Primary Endpoint

Complete Renal Response at Week 52 [n (%)]a

73 (40.8)

40 (22.5)

2.7 (95% CI:  1.6, 4.3);
p<0.001

Components of Primary Endpoint

UPCR ≤ 0.5 mg/mg [n (%)]

81 (45.3)

41 (23.0)

3.1 (95% CI:  1.9, 5.0)

eGFR ≥ 60 mL/min/1.73 m2 or no confirmed decrease
from baseline in eGFR of > 20% or no treatment- or
disease-related eGFR-associated adverse event b at time
of assessment [n (%)] [n (%)]

147 (82.1)

135 (75.8)

1.5 (95% CI:  0.8, 2.5)

eGFR = Estimated glomerular filtration rate, uPCR: Urine protein-creatinine ratio CI: Confidence interval,

  1. In order to be considered a responder, the patient must not have received more than 10 mg prednisone for ≥ 3 consecutive days or for ≥ 7 days in total during Weeks 44 through 52. Patients who received rescue medication or withdrew from the study were considered non-responders.
  2. Treatment- or disease-related eGFR-associated event is defined as blood creatinine increased, creatinine renal clearance decreased, glomerular filtration rate decreased, serum creatinine increased, renal impairment, renal failure, or renal failure acute.

LUPKYNIS Prescribing Information

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

  • Sex: LUPKYNIS worked similarly in men and women.
  • Race: LUPKYNIS worked similarly in White and Asian patients.
  • Age: The majority of patients were younger than 65 years of age, therefore the differences in how well LUPKYNIS worked between younger and older patients could not be determined.

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

The table below summarize subgroup results based on the primary endpoint analyses of LUPKYNIS compared with placebo in Trial 1.

Table 2. Effects of LUPKYNIS on Adjudicated Renal Response at Week 52, Stratified by Sex, Race, and Age Subgroups in Trial 1

Demographic Parameter

Response Rate %

Odds Ratio a

 

LUPKYNIS (N=179)

Placebo (N=178)

(95% CI)

Sex

Men

44.4%

19.2 %

4.1 (3.2, 5.1)

Women

40.4%

23.0 %

2.5 (2.2, 2.7)

Race

White

38.2 %

29.5 %

1.7 (1.3, 2.1)

Asian

41.5 %

17.9 %

4.0 (3.6, 4.5)

Other

43.1 %

19.7 %

3.7 (3.3, 4.2)

Age Group (years)

30 or younger

40.4

18.1

3.2 (2.1, 4.4)

Greater than 30

41.1

26.3

2.7 (2.3, 3.0)

a= Odds ratios and credible intervals include relevance of outcomes from other subgroups. In order to be considered a responder, the patient must not have received more than 10 mg prednisone for ≥ 3 consecutive days or for ≥ 7 days in total during Weeks 44 through 52. Patients who received rescue medication or withdrew from the study were considered non-responders.

Adapted from FDA Statistical Review

What are the possible side effects?

LUPKYNIS may cause serious side effects including increased risk of developing cancer, infection, kidney toxicity, high blood pressure, nervous system problems, high potassium, heart rhythm problems due to prolongation of heart electrical activity (QT prolongation), and low red blood cell count (anemia).

The most common side effects are kidney toxicity, high blood pressure, diarrhea, headache, anemia, cough, and urinary tract infection.

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

Below is the summary of the most common adverse reactions observed in patients treated with LUPKYNIS at the recommended dose or placebo in combined Trials 1 and 2.

Table 3. Adverse Reactions in ≥3% of Patients Treated with LUPKYNIS 23.7 mg Twice a Day and ≥2% Higher than Placebo in Trials 1 and 2

Adverse Reaction

 

LUPKYNIS
(n=267)

Placebo
(n=266)

Glomerular filtration rate decreased

26%

9%

Hypertension

19%

9%

Diarrhea

19%

13%

Headache

15%

8%

Anemia

12%

6%

Cough

11%

2%

Urinary tract infection

10%

6%

Abdominal pain upper

7%

2%

Dyspepsia

6%

3%

Alopecia

6%

3%

Renal Impairment

6%

3%

Abdominal pain

5%

2%

Mouth ulceration

4%

1%

Fatigue

4%

1%

Tremor

3%

1%

Acute kidney injury

3%

1%

Decreased appetite

3%

1%

LUPKYNIS Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The majority of patients were women. The differences in side effects between men and women were not analyzed.
  • Race: The occurrence of side effects was similar across racial groups.
  • Age: The majority of patients were younger than 65 years of age, therefore the differences in side effects between younger and older patients could not be determined.

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

The table below summarizes the occurrence of adverse events by race subgroups. Sex and age subgroups were not analyzed because the majority of patients were women and younger than 65 years of age.

Table 4. Subgroup Analysis of Treatment-Emergent Adverse Events (TEAE) by Race

Adverse Event

White

Asian

Black or African American

Other

LUPKYNIS

Placebo

LUPKYNIS

Placebo

LUPKYNIS

Placebo

LUPKYNIS

Placebo

Any TEAE, n/N (%)

83/98 (84.7)

79/103 (76.7)

101/105 (96.2)

89/92 (96.7)

29/29 (100)

22/24 (91.7)

31/35

(88.6)

42/47

(89.4)

Any Serious TEAE n/N (%)

18/98 (18.4)

22/103 (21.4)

31/105 (29.5)

15/92 (16.3)

7/29

(24.1)

8/24 (33.3)

5/35

(14.3)

5/47

(10.6)

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved LUPKYNIS based on evidence from two clinical trials (Trial 1/(NCT03021499), and Trial 2 /NCT02141672) of 533 patients with lupus nephritis. The trials were conducted at 221 sites in 47 countries including the United States.

The figure below summarizes how many men and women were in the clinical trials.

Figure 1. Demographics by Sex

Lupkynis Pie chart summarizing how many men and women were in the clinical trials.

Adapted from FDA Review

Figure 2 summarizes the percentage of patients by race in the clinical trials.

Figure 2. Demographics by Race

Pie chart summarizing how many patients of different races were in the clinical trial. In total, 201 patients were White (38%), 197 patients were Asian (37%), 53 patients were Black or African American (10%), and 82 patients were Other (15%).

Adapted from FDA Review

Figure 3 summarizes the percentage of patients by age in the clinical trials.

Figure 3. Demographics by Age

Pie chart summarizing how many individuals of certain age groups were in the clinical trial. In total, 530 patients were between 18-65 years old (99%) and 3 patients were older than 65 years old (1%).

Adapted from FDA Review

Figure 4 summarizes the percentage of patients by ethnicity in the clinical trials.

Figure 4. Demographics by Ethnicity

Pie chart summarizing how many individuals of certain ethnicity groups were in the clinical trial. In total, 137 patients were Hispanic or Latino (26%), and 395 patients were not Hispanic or Latino (74%), and 1 patient was unknown (1%).

Adapted from FDA Review

Who participated in the trials?

The table below summarize demographics of patients in pooled Trials 1 and 2.

Table 5. Trial Demographics (safety population)

 

LUPKYNIS
N=267

Placebo
N=266

TOTAL
N=533

Sex, n (%)

    Women

236 (88.4)

225 (84.6)

461 (86.5)

    Men

31 (11.6)

41 (15.4)

72 (13.5)

Race, n (%)

    Asian

105 (39.3)

92 (34.6)

197 (37.0)

    Black or African American

29 (10.9)

24 (9.0)

53 (9.9)

    White

98 (36.7)

103 (38.7)

201 (37.7)

    Other

35 (13.1)

47 (17.7)

82 (15.4)

Age, Median (Min, Max)

30 (18,66)

32 (18,72)

31 (18,72)

Age Group, n (%)

    18-65 years

266 (99.6)

264 (99.2)

530 (99.4)

    >65 years

1 (0.4)

2 (0.8)

3 (0.6)

Ethnicity, n (%)

    Hispanic or Latino

65 (24.3)

72 (27,1)

137 (25.7)

    Not Hispanic or Latino

202 (75.7)

193 (72.6)

395 (25.7)

    Unknown

0

1 (0.4)

1 (0.2)

Geographic Region, n (%)

    Asia

104 (38.9)

87 (32.7)

191 (35.9)

    Europe + South Africa

77 (28.8)

86 (32.3)

163 30.6)

    Americas

86 (32.3)

93 (35)

179 (33.6)

      United States

31 (11.6)

32 (12)

63 (11.8)

Adapted from FDA Review

How were the trials designed?

There were two trials that provided data for LUPKYNIS approval. Trials enrolled patients with lupus nephritis.

In Trial 1, patients were randomly assigned to receive by mouth LUPKYNIS or placebo for 52 weeks. Neither the patient nor the healthcare providers knew which medication was being given. The benefit of LUPKINYS in comparison to placebo was assess by proportion of patients who achieved a reduction in kidney inflammation. Data from this trial were also used for the assessment of side effects.

In Trial 2, patients were randomly assigned to receive by mouth one of two doses of LUPKYNIS or placebo for 48 weeks. Neither the patient nor the healthcare providers knew which medication was being given. Data from the trial were used for the assessment of side effects.

How were the trials designed?

There were two trials that provided data for LUPKYNIS approval in SLE patients with biopsy-proven active Class III or IV LN (alone or in combination with Class V LN) or Class V LN.

Trial 1 was a 52 week, double-blind, placebo-controlled trial in patients randomized in a 1:1 ratio to receive either LUPKYNIS 23.7 mg twice daily or placebo on background treatment with mycophenolate mofetil and corticosteroids.

The primary efficacy endpoint was the proportion of patients achieving complete renal response at Week 52. Complete renal response was defined as follows (both must be met):

  • UPCR of ≤0.5 mg/mg, and
  • eGFR ≥ 60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of > 20% or no treatment- or disease-related eGFR-associated event (defined as blood creatinine increased, creatinine renal clearance decreased, glomerular filtration rate decreased, serum creatinine increased, renal impairment, renal failure, or renal failure acute) at time of assessment.

In order to be considered a responder, the patient must not have received more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during Weeks 44 through 52. Patients who received rescue medication or withdrew from the study were considered non-responders.

Trial 2 was a 48 week, double-blind, placebo-controlled trial in patients randomized in a 1:1:1 ratio to receive either LUPKYNIS 23.7 mg twice daily, voclosporin 39.5 mg twice daily or placebo on background treatment with mycophenolate mofetil and corticosteroids. Data from this trial were used for safety assessment.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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