Use of LUPKYNIS was safe and well tolerated in
patients for up to three years of treatment, with no new safety
signals
In AURORA 2, long-term treatment with LUPKYNIS
led to a clinically relevant preservation of kidney function in LN
patients
A pooled analysis from the AURA-LV and AURORA 1
studies, also presented at ERA, showed early treatment response to
LUPKYNIS with reductions in proteinuria across lupus nephritis
biopsy classes
Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH) (Aurinia or the
Company), a biopharmaceutical company committed to delivering
therapeutics that change the course of autoimmune disease, today
presented for the first time the results of the AURORA 2
continuation study evaluating the long-term safety and tolerability
of LUPKYNIS™ (voclosporin) for the treatment of adults with active
lupus nephritis (LN), a serious complication in patients with
systemic lupus erythematosus (SLE). The results were presented
during an oral session at the 59th European Renal Association (ERA)
Congress, held in Paris and virtually May 19-22, 2022.
The AURORA 2 study assessed long-term safety and tolerability of
voclosporin compared to placebo (both taken in combination with
mycophenolate mofetil (MMF) and low-dose oral steroids) in patients
with LN receiving treatment for an additional 24 months following
completion of one year on treatment in the AURORA 1 study. The
primary endpoint was safety and included assessments of adverse
events, deaths, and hematological assessments. Secondary endpoints
include renal response, renal flare, renal outcomes, and changes in
urine protein to creatinine ratio (UPCR) and estimated glomerular
filtration rate (eGFR).
“Lupus nephritis is a severe complication of lupus that will
occur in up to half of patients diagnosed with SLE,” said Y.K. Onno
Teng, M.D., Ph.D., Leiden University Medical Center, Leiden, The
Netherlands, presenting author of the AURORA 2 ERA presentation and
principal study investigator. “These results demonstrated that
patients on long-term voclosporin therapy continue to experience
clinically relevant benefits, including significant preservation of
kidney function long-term, with no unexpected, new safety
signals.”
Voclosporin was well tolerated during the study period with a
similar safety profile to control and no unexpected safety signals.
Specific findings included:
- Overall rates of serious adverse events were similar in both
the control (28.0%) and voclosporin (26.0%) arms and there was no
increase in infectious events.
- Generally adverse events were low and decreased over time on
treatment.
- Significant and meaningful reductions in proteinuria achieved
in AURORA 1 were maintained.
- In AURORA 2, there was a significant difference in eGFR slope
in favor of voclosporin (-0.2 mL/min/1.73 m2) compared to control
arm (-5.4 mL/min/1.73 m2).
- There was a small, expected, and early decrease in mean eGFR in
the first four weeks of treatment in AURORA 1, after which eGFR
remained stable through the end of AURORA 2.
- The mean UPCR was lower in the voclosporin-treated groups at
all time points during the three years.
- There were four deaths in the active control group during
AURORA 2, while none in the voclosporin-treated group.
“When treating patients with lupus nephritis, the ultimate goal
is to preserve kidney function,'' said Neil Solomons, M.D., Chief
Medical Officer at Aurinia. “We’re thrilled to build out the body
of data that reinforces voclosporin as a safe and effective
treatment option for lupus nephritis patients over the long
term.”
A post-hoc analysis of pooled data from the AURA-LV and AURORA 1
studies was also presented during an oral session at the ERA
Congress and examined the impact of voclosporin on the time to
proteinuria reduction by biopsy class. The analysis reviewed pure
class III, class IV, and class V biopsy groups and showed patients
treated with voclosporin in addition to MMF and low dose steroids
achieved earlier reductions in proteinuria across biopsy classes.
These results support the efficacy results observed in the AURA-LV
and AURORA 1 trials respectively, indicating a faster time to
response when voclosporin is added to MMF and low-dose steroid
treatment.
“The breadth of the AURORA clinical program provides important
insights demonstrating the efficacy of voclosporin for the
treatment of lupus nephritis across varying patient types," said
Anca Askanase, M.D., M.P.H., Columbia University Medical Center and
presenting author of the AURA-LV and AURORA 1 pooled analysis.
"This analysis strengthens the clinical evidence supporting
voclosporin as an important option that physicians can use in
addition to the current standard of care treatment regimen to
rapidly control lupus nephritis and protect kidney function.”
AURORA 2 Study Design
AURORA 2 (NCT03597464) is a Phase 3 randomized, double-blind,
placebo-controlled clinical trial to assess the long-term safety
and tolerability of voclosporin, in addition to MMF/steroids.
Patients who completed 12 months of treatment in the Phase 3 AURORA
1 study were eligible to enroll in the AURORA 2 continuation study
with the same randomized treatment of voclosporin at 23.7 mg twice
daily or placebo, in combination with MMF at 1 g twice daily with
low-dose oral steroids, for up to an additional 24 months. A total
of 216 LN patients continued into AURORA 2, with 116 patients in
the voclosporin-treated group and 100 patients in the active
control group.
About AURORA 1
The AURORA 1 study was a 52-week study designed to evaluate the
efficacy and safety of LUPKYNIS (23.7 mg twice daily) when added to
background therapy of MMF and corticosteroids tapered to a low
dose, compared to background therapy alone in an ethnically and
racially diverse patient population with active LN. Three hundred
fifty-seven patients with a diagnosis of SLE and LN according to
the American College of Rheumatology criteria and a kidney biopsy
within two years that showed Class III, IV and/or V LN were
enrolled. AURORA 1 met its primary endpoint, achieving
statistically superior complete renal response rates of 41% in the
LUPKYNIS group versus 23% in the control group (odds ratio [OR]
2.65, 95% confidence interval [CI] 1.64-4.27; p < 0.0001).
LUPKYNIS also achieved statistical significance in all
pre-specified hierarchical secondary endpoints, including reduced
time to 50% reduction from baseline in UPCR and time to UPCR
<0.5 mg/mg compared to control. The primary endpoint was
complete renal response at 52 weeks defined as urine protein
creatinine ratio (UPCR) ≤0.5 mg/mg, with stable renal function
(defined as estimated glomerular filtration rate [eGFR] ≥60
mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of
>20%), no administration of rescue medication, and no more than
10 mg prednisone equivalent per day for three or more consecutive
days or for seven or more days during Weeks 44 through 52. LUPKYNIS
was well tolerated with no unexpected safety signals. Serious
adverse events (SAEs) were reported in 21% of those treated with
LUPKYNIS and in 21% of those in the control group. Results from the
completed AURORA 1 study (NCT03021499) were published in May 2021
in The Lancet.
About AURA-LV
The AURA–LV study (Aurinia Urinary protein Reduction in Active
Lupus with Voclosporin) was a 48-week study comparing the efficacy
of two doses of voclosporin added to current standard of care of
MMF against standard of care with placebo in achieving CR in
patients with active LN. All arms also received low doses of
steroids as background therapy. 265 patients were enrolled at
centers in 20 countries worldwide. On entry to the study, patients
were required to have a diagnosis of LN according to established
diagnostic criteria (American College of Rheumatology) and clinical
and biopsy features indicative of highly active nephritis. The
24-week primary and secondary endpoints were released in Q3 2016
where the primary and all secondary endpoints were met. Complete
remission (CR) is a composite endpoint that includes: confirmed
UPCR of ≤0.5 mg/mg; normal, stable renal function (≥60
mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of
≥20%); presence of sustained, low dose steroids (≤10mg prednisone
from week 16-24); and no administration of rescue medications.
Partial remission (PR) in the trial is measured by a ≥50% reduction
in UPCR with no concomitant use of rescue medication.
About Lupus Nephritis
LN is a serious manifestation of SLE, a chronic and complex
autoimmune disease. About 200,000-300,000 people live with SLE in
the U.S. and about one-third of these people are diagnosed with LN
at the time of their SLE diagnosis. About 50 percent of all people
with SLE may go on to develop LN. If poorly controlled, LN can lead
to permanent and irreversible tissue damage within the kidney,
resulting in kidney failure. Black and Asian individuals with SLE
are four times more likely to develop LN and individuals of
Hispanic ancestry are approximately twice as likely to develop the
disease when compared with Caucasian individuals. Black and
Hispanic individuals with SLE also tend to develop LN earlier and
have poorer outcomes when compared to Caucasian individuals.
About LUPKYNIS
LUPKYNIS™ is the first FDA-approved oral medicine for the
treatment of adult patients with active LN. LUPKYNIS is a novel,
structurally modified calcineurin inhibitor (CNI) with a dual
mechanism of action, acting as an immunosuppressant through
inhibition of T-cell activation and cytokine production and
promoting podocyte stability in the kidney. The recommended
starting dose of LUPKYNIS is three capsules twice daily with no
requirement for serum drug monitoring. Dose modifications can be
made based on Aurinia’s proprietary personalized eGFR-based dosing
protocol. Boxed Warning, warnings and precautions for LUPKYNIS are
consistent with those of other CNI-immunosuppressive
treatments.
About Aurinia
Aurinia Pharmaceuticals is a fully integrated biopharmaceutical
company focused on delivering therapies to treat targeted patient
populations that are impacted by serious diseases with a high unmet
medical need. In January 2021, the Company introduced LUPKYNIS™
(voclosporin), the first FDA-approved oral therapy for the
treatment of adult patients with active lupus nephritis (LN). The
Company’s head office is in Victoria, British Columbia, its U.S.
commercial hub is in Rockville, Maryland, and the Company focuses
its development efforts globally.
Investor and Media:
INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATIONS
LUPKYNIS is indicated in combination with a background
immunosuppressive therapy regimen for the treatment of adult
patients with active LN. Limitations of Use: Safety and efficacy of
LUPKYNIS have not been established in combination with
cyclophosphamide. Use of LUPKYNIS is not recommended in this
situation.
IMPORTANT SAFETY INFORMATION
BOXED WARNINGS: MALIGNANCIES AND SERIOUS INFECTIONS
Increased risk for developing malignancies and serious
infections with LUPKYNIS or other immunosuppressants that may lead
to hospitalization or death.
CONTRAINDICATIONS
LUPKYNIS is contraindicated in patients taking strong CYP3A4
inhibitors because of the increased risk of acute and/or chronic
nephrotoxicity, and in patients who have had a serious/severe
hypersensitivity reaction to LUPKYNIS or its excipients.
WARNINGS AND PRECAUTIONS
Lymphoma and Other Malignancies: Immunosuppressants, including
LUPKYNIS, increase the risk of developing lymphomas and other
malignancies, particularly of the skin. The risk appears to be
related to increasing doses and duration of immunosuppression
rather than to the use of any specific agent.
Serious Infections: Immunosuppressants, including LUPKYNIS,
increase the risk of developing bacterial, viral, fungal, and
protozoal infections (including opportunistic infections), which
may lead to serious, including fatal, outcomes.
Nephrotoxicity: LUPKYNIS, like other CNIs, may cause acute
and/or chronic nephrotoxicity. The risk is increased when CNIs are
concomitantly administered with drugs associated with
nephrotoxicity.
Hypertension: Hypertension is a common adverse reaction of
LUPKYNIS therapy and may require antihypertensive therapy.
Neurotoxicity: LUPKYNIS, like other CNIs, may cause a spectrum
of neurotoxicities: severe include posterior reversible
encephalopathy syndrome (PRES), delirium, seizure, and coma; others
include tremor, paresthesia, headache, and changes in mental status
and/or motor and sensory functions.
Hyperkalemia: Hyperkalemia, which may be serious and require
treatment, has been reported with CNIs, including LUPKYNIS.
Concomitant use of agents associated with hyperkalemia may increase
the risk for hyperkalemia.
QTc Prolongation: LUPKYNIS prolongs the QTc interval in a
dose-dependent manner when dosed higher than the recommended lupus
nephritis therapeutic dose. The use of LUPKYNIS in combination with
other drugs that are known to prolong QTc may result in clinically
significant QT prolongation.
Immunizations: Avoid the use of live attenuated vaccines during
treatment with LUPKYNIS. Inactivated vaccines noted to be safe for
administration may not be sufficiently immunogenic during treatment
with LUPKYNIS.
Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA)
have been reported in patients treated with another CNI
immunosuppressant. If PRCA is diagnosed, consider discontinuation
of LUPKYNIS.
Drug-Drug Interactions: Avoid co-administration of LUPKYNIS and
strong CYP3A4 inhibitors or with strong or moderate CYP3A4
inducers. Reduce LUPKYNIS dosage when co-administered with moderate
CYP3A4 inhibitors. Reduce dosage of certain P-gp substrates with
narrow therapeutic windows when co-administered.
ADVERSE REACTIONS
The most common adverse reactions (>3%) were glomerular
filtration rate decreased, hypertension, diarrhea, headache,
anemia, cough, urinary tract infection, abdominal pain upper,
dyspepsia, alopecia, renal impairment, abdominal pain, mouth
ulceration, fatigue, tremor, acute kidney injury, and decreased
appetite.
SPECIFIC POPULATIONS
Pregnancy/Lactation: May cause fetal harm. Advise not to
breastfeed.
Renal Impairment: Not recommended in patients with baseline eGFR
≤45 mL/min/1.73 m2 unless benefit exceeds risk. Severe renal
impairment: Reduce LUPKYNIS dose.
Mild and Moderate Hepatic Impairment: Reduce LUPKYNIS dose.
Severe hepatic impairment: Avoid LUPKYNIS use.
Please see Prescribing Information, including Boxed
Warning, and Medication Guide for LUPKYNIS
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220520005341/en/
Media: Dana Lynch Corporate Communications, Aurinia
dlynch@auriniapharma.com
Investors: aurinia@westwicke.com
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