Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the
Company) today announced the results of a post-hoc, pooled analysis
of the Phase 2 AURA-LV (NCT02141672) and Phase 3 AURORA 1
(NCT03021499) studies, which found that LUPKYNIS® with
mycophenolate mofetil (MMF) and low-dose steroids resulted in
earlier and greater reductions in proteinuria in lupus nephritis
(LN) patients with high proteinuria across biopsy classes, races,
and ethnicities. These data were presented at the European Congress
of Rheumatology, EULAR 2023, in Milan, Italy.
Consistent with results from the overall pooled study
population, patients with urine protein creatinine ratio (UPCR) ≥2
g/g at baseline treated with LUPKYNIS® achieved significantly
higher renal response rates than patients treated with MMF and
low-dose steroids alone, regardless of baseline demographics or
clinical characteristics.
“Proteinuria is a common manifestation of LN that can lead to
progressive kidney damage. Early reductions in UPCR have been shown
to be predictive of improved long-term outcomes in LN. Yet, there
remains the need for safe and effective therapies for patients with
high proteinuria, especially given that monoclonal antibody
therapies have demonstrated limited efficacy in LN patients with
moderate to high proteinuria. These findings for voclosporin, a
novel calcineurin inhibitor, are clinically relevant and can help
improve renal outcomes for LN patients,” said lead study author
Emily Littlejohn, D.O., M.P.H., Cleveland Clinic Main Campus,
Rheumatologic and Immunologic Disease, Cleveland, Ohio.
“We are pleased to present these findings that further support
the efficacy and safety of a voclosporin-based treatment regimen
across diverse LN patient populations. In this analysis, complete
response rates favored voclosporin regardless of sex, race,
ethnicity, baseline UPCR or baseline renal function. Patients who
achieved complete renal response with voclosporin experienced
stable renal function while undergoing a rapid steroid taper as
part of the study. These findings further differentiate LUPKYNIS, a
next-generation CNI, from legacy, first-generation CNIs,” said Dr.
Greg Keenan, Chief Medical Officer of Aurinia.
About the Analysis
To further characterize the efficacy and safety of voclosporin
in patients with high proteinuria, outcomes were analyzed in
various subpopulations of patients with UPCR ≥2 g/g at baseline
using the pooled dataset from the Phase 2 AURA-LV and Phase 3
AURORA 1 studies.
Both studies enrolled patients with biopsy-proven LN (Class III,
IV, or V ± III/IV) within 6 months (or up to 2 years in AURORA 1)
and proteinuria ≥1.5 g/g (≥2 g/g for Class V). Patients were
randomized to voclosporin (23.7 mg BID) or placebo and treated for
up to one year (48 weeks in AURA-LV and 52 weeks in AURORA 1). All
patients received MMF and low-dose steroids. Protocol-defined
glucocorticoid taper included intravenous methylprednisolone on
Days 1 and 2. Oral glucocorticoid was initiated on Day 3 with 20-25
mg/day prednisone and tapered to a target dose of 2.5 mg/day at
Week 16 and thereafter.
For the analysis, complete renal response (CRR) rates were
evaluated in patients with baseline UPCR ≥2 g/g. CRR was defined as
UPCR ≤0.5 g/g with stable renal function, low-dose steroids, and no
rescue medication. Subgroup analyses were based on sex, age, race,
ethnicity, biopsy class, and estimated glomerular filtration rate
(eGFR) at baseline. Adverse events (AEs) and mean eGFR levels over
time were also assessed.
Of the 268 and 266 patients included in the voclosporin and
control arms of the pooled analysis, respectively, 217 and 215
patients had a baseline UPCR ≥2 g/g (mean [SD], 5.1 [3.3] vs. 4.6
[2.8] g/g, respectively). At one year, the change from baseline in
least squares mean UPCR was -3.8 (0.1) g/g in the voclosporin arm,
compared to -3.1 (0.2) g/g in the control arm (difference vs.
control, -0.7; p=0.0003).
A significantly greater percentage of voclosporin-treated
patients achieved CRR at one year compared to the control arm
(41.0% vs. 21.9%; odds ratio [OR] 2.48). Across biopsy classes, the
highest rates of CRR were observed in Class III patients treated
with voclosporin (50% vs. 16.1% in control, p=0.0126), followed by
Class IV (44% vs. 23.8%, p=0.0019), Class V with III or IV lesions
(37.7% vs. 17% p=0.0306), and Class V (31.3% vs. 28.6%,
p=0.81).
CRR rates were numerically greater in subgroups of
voclosporin-treated patients, including both sexes and across all
ages, races, ethnicities, biopsy classes, and eGFR levels assessed,
as indicated with OR>1.
Similar rates of AEs were reported in both arms and mean eGFR
levels were similar and stable over one year of treatment.
About Lupus Nephritis
Lupus Nephritis is a serious manifestation of systemic lupus
erythematosus (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 lupus nephritis at the
time of their SLE diagnosis. About 50 percent of all people with
SLE may develop lupus nephritis. If poorly controlled, lupus
nephritis can lead to permanent and irreversible tissue damage
within the kidney. Black and Asian people with SLE are four times
more likely to develop lupus nephritis and Hispanic people are
approximately twice as likely to develop the disease compared to
White people with SLE. Black and Hispanic people with SLE also tend
to develop lupus nephritis earlier and have worse outcomes,
compared to White people with SLE.
About LUPKYNIS®
LUPKYNIS® is the first U.S. FDA- and EC-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 with high unmet medical needs that are impacted by
autoimmune, kidney and rare diseases. In January 2021, the Company
introduced LUPKYNIS® (voclosporin), the first FDA-approved oral
therapy dedicated to the treatment of adult patients with active
lupus nephritis. The Company’s head office is in Edmonton, Alberta,
its U.S. commercial office is in Rockville, Maryland. The Company
focuses its development efforts globally.
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.
Reference
Littlejohn E et al. Efficacy and Safety of Voclosporin across
Patient Subgroups with Proteinuria ≥2 mg/mg: An Integrated Analysis
of the AURA-LV and AURORA 1 Studies. Presented at EULAR 2023.
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version on businesswire.com: https://www.businesswire.com/news/home/20230601005393/en/
Media Inquiries: Andrea Christopher, Corporate
Communications Director, Aurinia achristopher@aurinia.com
Investor Inquiries: Aurinia@westwicke.com
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