- LUPKYNIS® achieved significantly earlier reductions in UPCR and
significantly higher renal response rates in lupus nephritis
patients with high proteinuria, compared to patients treated with
mycophenolate mofetil and low-dose steroids alone, in a pooled,
post-hoc analysis.1
- LUPKYNIS® was associated with a higher rate of renal secretion
and lower overall exposure to kidney tissue, which may be
associated with an improved safety profile, compared to
cyclosporine and tacrolimus, in an animal study.2
- LUPKYNIS® did not inhibit the kidney tubular reabsorption of
calcium and magnesium and therefore does not cause hypercalciuria
or hypomagnesemia, in contrast to tacrolimus, in an animal
study.3
Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the
Company) today announced three oral presentations at the Annual
Meeting of the European Renal Association (ERA), providing
additional support for the efficacy and safety of LUPKYNIS®
(voclosporin), a next generation calcineurin inhibitor (CNI)
approved in the U.S. and Europe for the treatment of adults with
active lupus nephritis (LN).
One oral presentation included results of a post-hoc, pooled
analysis of the Phase 2 AURA-LV (NCT02141672) and Phase 3 AURORA 1
(NCT03021499) studies showing that LUPKYNIS® taken with
mycophenolate mofetil (MMF) and low-dose steroids resulted in
significantly higher renal response rates and significantly earlier
reductions in UPCR in LN patients with high proteinuria (≥2 mg/mg),
compared to MMF and low-dose steroids alone.1 These findings are
meaningful, as recent post-hoc analyses with monoclonal antibody
therapies demonstrated limited efficacy in patients with LN and
moderate to high proteinuria (UPCR ≥2 to ≥3 mg/mg), potentially due
to an increase in renal antibody clearance.4-7
“Lupus nephritis is a common and serious manifestation of lupus
and can lead to significant kidney damage without appropriate
treatment. The findings presented at ERA this week show that
voclosporin achieved a 50% proteinuria reduction at 28 days,
compared to 57 days in the control arm (p<0.0001). Additionally,
the median time to achieving a UPCR of ≤0.5 mg/mg was 211 days in
the voclosporin arm, while less than 50% of patients in the control
arm ever achieved this endpoint,” said Dr. Greg Keenan, Chief
Medical Officer of Aurinia. “Additionally, in two pre-clinical
animal models, voclosporin showed a higher rate of renal secretion,
lower overall kidney exposure, and no associated hypercalciuria or
hypomagnesemia, compared to the legacy, first-generation CNIs.
These results are relevant, as they demonstrate important clinical
and mechanistic findings associated with voclosporin
treatment.”
An oral presentation of a study assessing kidney tissue in mice
treated with voclosporin (VCS), tacrolimus (TAC), and cyclosporine
(CSA) revealed differential retention and distribution of these
three therapies, consistent with their respective renal clearances
in humans. Higher drug exposure and >90% renal reabsorption was
observed for both CSA and TAC in this study, whereas the renal
handling of VCS suggested a significant component of tubular
secretion. The higher rate of secretion and lower overall exposure
of kidney tissue to VCS may be associated with an improved safety
profile when compared to the more diffuse distribution and greater
renal retention of CSA and TAC.2
Another oral presentation compared the effects of TAC and VCS on
calcium and magnesium levels in rats. Clinically, TAC frequently
causes hypercalciuria and hypomagnesemia by inhibiting kidney
tubular calcium and magnesium reabsorption. The study found that,
unlike TAC, VCS does not inhibit the kidney tubular reabsorption of
calcium and magnesium and therefore does not cause hypercalciuria
or hypomagnesemia. The data showed that the tubulotoxicity observed
with TAC is not apparent with VCS treatment at clinically relevant
doses.3
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, and 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
- Almaani S et al. Efficacy and Safety of Voclosporin in Patients
with Proteinuria ≥2 mg/mg: An Integrated Analysis of the AURA-LV
and AURORA 1 Studies. Presented at the European Renal Associate
Annual Meeting, 2023, Milan, Italy.
- Zhou S et al. Selective renal tissue disposition of the
calcineurin inhibitors voclosporin, cyclosporine, and tacrolimus.
Presented at the European Renal Associate Annual Meeting, 2023,
Milan, Italy.
- Wei Ky et al. Tacrolimus but not voclosporin inhibits kidney
tubular calcium and magnesium reabsorption in rats at clinically
therapeutic doses. Presented at the European Renal Associate Annual
Meeting, 2023, Milan, Italy.
- Furie RA et al. Ann Rheum Dis. 2022;81:100-107.
- Jayne D et al. Ann Rheum Dis. 2022;81(4):496-506.
- Liu T et al. Lupus. Apr 2022;31(4):424-432.
- Rovin BH et al. Kidney Int. Feb 2022;101(2):403-413.
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version on businesswire.com: https://www.businesswire.com/news/home/20230620508139/en/
Media Inquiries: Andrea Christopher, Corporate
Communications Director, Aurinia achristopher@aurinia.com
Investor Inquiries: Aurinia@westwicke.com
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