Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the
Company) today announced that full results from the Phase 3,
double-blind, placebo-controlled AURORA 2 extension study were
published online in Arthritis & Rheumatology, the official
peer-reviewed journal of the American College of Rheumatology.
As part of the AURORA Clinical Program, the AURORA 2 extension
study assessed the long-term safety and tolerability of LUPKYNIS®
(voclosporin), compared with placebo, in combination with
mycophenolate mofetil and low-dose glucocorticoids, to treat active
lupus nephritis (LN) in adult patients who completed one year of
treatment in the Phase 3 AURORA 1 clinical trial.
Voclosporin was well tolerated with no new or worsening safety
signals in the extension study. Clinical efficacy over three years
of treatment was maintained, as observed by maintenance of urine
protein creatinine ratio (UPCR) reductions, sustained complete
renal response (CRR) and preserved kidney function, suggesting a
positive benefit-risk profile for voclosporin in LN patients.
“Proteinuria, a defining part of the characterization of chronic
kidney disease, often precedes a decline in kidney function and is
associated with progression to kidney failure. Reductions in
proteinuria are critical for slowing or stopping progression to
end-stage kidney disease and improving long-term outcomes for LN
patients. Notably, in this extension study, kidney preservation,
sustained renal response, and reductions in steroid use were
achieved with voclosporin. These findings demonstrate the critical
importance of voclosporin in the management of LN to improve
patient outcomes,” said lead study author Amit Saxena, MD, Division
of Rheumatology, New York University Grossman School of
Medicine.
Estimated glomerular filtration rate (eGFR), an important
measurement of kidney function, remained stable throughout the
extension study. The slope of the change in eGFR over the extension
study period at month 36 demonstrated kidney function preservation
in the voclosporin group (-0.2 mL/min/1.73m2), compared with a
decline in function after one year in the control group (-5.4
mL/min/1.73m2).
There was a significant increase in achievement of CRR in LN
patients treated with voclosporin, compared to patients in the
control group, at nearly every time point in the AURORA Clinical
Program. At month 12, CRR occurred in 52.6% of patients who
received voclosporin, compared to 34.0% in the control group,
largely driven by achieving a proteinuria reduction in UPCR to ≤0.5
mg/mg. At month 36, CRR occurred in 50.9% of patients who received
voclosporin, compared to 39.0% of patients in the control group.
CRR was defined as UPCR of ≤0.5 mg/mg, eGFR ≥60 ml/min/1.73 m2 or
no confirmed decrease from pretreatment baseline in eGFR of
>20%, no rescue medication received for LN, and not receiving
more than 10 mg of glucocorticoids for ≥3 consecutive days or for
≥7 days in total during the eight weeks prior to renal response
assessment.
These results were achieved with most patients in both groups
(>75%) maintaining glucocorticoid tapering throughout the study
and receiving doses of ≤2.5 mg/day at the end of the extension
study.
Of those who experienced adverse events (AEs) in the extension
study, most were mild or moderate (86% in the voclosporin group vs.
81% in the control group). Across three years of treatment,
infections were the most common type of AE (69.8% in the
voclosporin group vs. 72.0% in the control group), with low rates
of serious infections in both groups (12.9% in the voclosporin
group vs. 17.0% in the control group). Most adverse events declined
annually over the study period, with 86.1% of patients completing
the two-year extension.
“The results of this extension study reinforce the long-term
safety and effectiveness of LUPKYNIS to stabilize kidney function
in those diagnosed with LN, a debilitating, yet common complication
that occurs in about half of people with lupus,” said Dr. Greg
Keenan, Chief Medical Officer of Aurinia. “Together, AURA-LV,
AURORA 1, and AURORA 2 represent one of the largest and longest
placebo-controlled clinical programs evaluating the treatment of
LN. We are proud of our sustained research in autoimmune diseases
like lupus and remain committed to helping improve kidney health
for people living with lupus nephritis.”
About the AURORA Clinical Program In AURORA 1
(NCT03021499), a 12-month, phase 3, double-blind,
randomized-controlled pivotal study, the efficacy and safety of
voclosporin was compared with a control group in achieving CRR in
patients with LN. AURORA 1 demonstrated the clinical superiority of
voclosporin with mycophenolate mofetil (MMF) and low-dose
glucocorticoids compared to MMF and low-dose glucocorticoids alone.
Significantly more patients in the voclosporin group achieved a CRR
at 52 weeks of treatment and did so significantly faster than those
in the control group. The safety profile in AURORA 1 was comparable
between treatment groups, in line with previous studies; no new
safety concerns were observed. Results from the completed Phase 3
randomized, double-blind, placebo-controlled, multicenter AURORA 1
study were published in The Lancet.
AURORA 2 (NCT03597464) is a Phase 3, double-blind, extension
study to assess the long-term safety and tolerability of
voclosporin, in addition to MMF and low-dose glucocorticoids, for
the treatment of patients with active LN. Patients who completed 12
months of treatment in the Phase 3 AURORA 1 study were eligible to
enroll in the AURORA 2 extension study with the same randomized
treatment of voclosporin or placebo, in combination with MMF
(target dose of 2 g/day) and low-dose glucocorticoids (target dose
of ≤2.5 mg/day), for an additional 24 months.
A total of 216 LN patients continued into the extension study,
with 116 patients in the voclosporin group and 100 patients in the
control group; 90 and 78 patients, respectively, received 36 months
of total treatment at the completion of the study. Study drug dose
changes decreased over time.
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. Food and Drug
Administration and European Commission-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.
References: Saxena A., Ginzler E., Gibson K., Satirapoj
B., Santillán A., Levchenko O., Navarra S., Atsumi T., Yasuda S.,
Chavez-Perez N., Arriens C., Parikh S., Caster D., Birardi V.,
Randhawa S., Lisk L., Huizinga R., Teng O. (2023), Safety and
Efficacy of Long-Term Voclosporin Treatment for Lupus Nephritis in
The Phase 3 AURORA 2 Clinical Trial. Arthritis Rheumatol. Accepted
Author Manuscript:
https://onlinelibrary.wiley.com/doi/abs/10.1002/art.42657
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version on businesswire.com: https://www.businesswire.com/news/home/20230719522419/en/
Media Inquiries: Andrea Christopher, Corporate
Communications Director, Aurinia achristopher@auriniapharma.com
Investor Inquiries: Aurinia@westwicke.com
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