- A propensity analysis of AURORA 1 suggested that initial
therapy with LUPKYNIS® plus standard of care improved safety and
demonstrated earlier reductions in proteinuria when compared to a
conventional regimen consisting of higher doses of both
mycophenolate mofetil and glucocorticoids alone.
- Patients treated with LUPKYNIS® in a repeat kidney biopsy
sub-study achieved improvement in histologic activity with stable
chronicity scores and no evidence of chronic injury.
- A post-hoc, pooled analysis of Phase 2 and 3 studies showed
LUPKYNIS® achieved significantly higher complete renal response in
lupus nephritis patients with proteinuria >=2 g/day compared to
patients treated with MMF and low-dose glucocorticoids alone.
- A post-hoc analysis showed Black patients experienced improved
outcomes and better complete renal response when using
LUPKYNIS®.
- Additional poster presentations provided insights into the
ongoing lupus nephritis registry Enlight-LN and the disposition of
LUPKYNIS® compared to first-generation calcineurin inhibitors in
renal tissue.
Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the
Company), announced today the presentation of five studies (one
oral and four posters) at the annual American College of
Rheumatology Convergence 2023 taking place in San Diego, CA,
November 10-15. The data reinforce previous findings on the safety
and effectiveness of LUPKYNIS® (voclosporin), a second generation
calcineurin inhibitor (CNI), for the treatment of adult patients
with active lupus nephritis (LN), as shown in the AURORA Clinical
Program, comprised of the Phase 3 AURORA 1 clinical trial and the
Phase 3 AURORA 2 extension study.
An oral presentation demonstrated that initial therapy with
LUPKYNIS® plus standard of care reduced proteinuria and patient
exposure to toxicities, compared to a conventional regimen
consisting of higher doses of both mycophenolate mofetil (MMF) and
glucocorticoids alone. Safety and efficacy outcomes for
propensity-matched patients with active LN from the Aspreva Lupus
Management Study (ALMS) and the AURORA 1 study were assessed at
three and six months. In ALMS, MMF was dosed to a target of 3 g/day
with oral glucocorticoids initiated at a maximum dose of 60 mg/day
and tapered every two weeks to 10 mg/day. In AURORA 1, patients
received LUPKYNIS® 23.7 mg BID in combination with MMF (target dose
2 g/day) and oral glucocorticoids (starting dose of 25 mg/day
tapered to 2.5 mg/day by Week 16). The data showed an improved
safety profile over the first six months of treatment with
LUPKYNIS® in combination with low-dose glucocorticoids and
lower-dose MMF without compromising efficacy.
“The findings from the propensity analysis of the ALMS and
AURORA 1 studies support the use of a triple immunosuppressive
regimen containing LUPKYNIS® for the treatment of active LN.
Conventional therapeutic regimens for LN have incomplete efficacy
and significant toxicities. This study adds to the growing body of
data supporting the evolving treatment paradigm for LN,” said lead
study author Maria Dall’Era, M.D., Chief and Professor of Medicine
in the Division of Rheumatology, University of California, San
Francisco.
A post-hoc, pooled analysis of the Phase 2 AURA-LV and Phase 3
AURORA 1 studies found that LUPKYNIS® with MMF and low-dose
glucocorticoids resulted in earlier and greater reductions in
proteinuria in LN patients with proteinuria >=2 g/day and
greater numeric achievement of complete renal response across
biopsy classes, races, and ethnicities. 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 complete renal response
rates at one year than patients treated with MMF and low-dose
steroids alone, regardless of baseline demographics or clinical
characteristics.
“The research presented at ACR this week further supports the
importance of a LUPKYNIS-based treatment regimen to help preserve
kidney function in LN patients by producing earlier and greater
reductions in proteinuria while allowing patients to maintain
stable renal function. 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,” said
Dr. Greg Keenan, Chief Medical Officer of Aurinia.
To characterize the long-term renal impact of LUPKYNIS® at the
histologic level, researchers analyzed repeat kidney biopsies from
a subset of patients in AURORA 2, including 16 patients in the
active treatment arm who received LUPKYNIS® in combination with MMF
and low-dose glucocorticoids and 10 patients in the control arm
treated with MMF and low-dose glucocorticoids alone. Histologic
changes from baseline to approximately 18 months post-treatment
were assessed. Across both study arms, activity scores, which
measured active inflammation in LN, improved to a similar degree,
while the chronicity scores, a measure of irreversible kidney
injury, remained stable. These results confirmed the safety profile
of LUPKYNIS® showing no associated chronic injury with use.
Importantly, patients treated with LUPKYNIS® in the overall AURORA
2 cohort maintained stable renal function over the last two years
of the study, as measured by eGFR slope analysis, and experienced
numerically greater mean reductions in UPCR, compared to patients
in the control arm. These results were also recently presented at
the annual American Society of Nephrology Kidney Week 2023.
In a subset analysis of three years of data from the AURORA
Clinical Program, 44.4% of Black patients treated with LUPKYNIS®
experienced an improvement in complete renal response at 36 months
(n=18) compared to 14.3% of Black patients who achieved complete
renal response when treated with MMF and glucocorticoids alone (n=
7 OR: 4.17 (Ci; 0.41, >9.99), p=0.22). These findings among
Black patients, a population that often experiences worse outcomes
and lower responses to LN treatment, are consistent with the
treatment response seen across all racial and ethnic groups treated
with LUPKYNIS® in the AURORA Clinical Program. These results were
also recently presented at the annual American Society of
Nephrology Kidney Week 2023.
Additional data assessed the disposition of cyclosporine (CSA),
tacrolimus (TAC), and voclosporin (VCS) in mouse kidneys relative
to its systemic drug exposure. The study found differential
retention and distribution of the three therapies in mice,
consistent with findings from a literature review of their systemic
and renal clearance in humans. The assessment of mouse kidneys
showed that CSA and TAC had higher drug exposure, while the
literature review showed ˃90% renal reabsorption in humans for CSA
and TAC. Comparatively, renal handling of VCS suggested significant
tubular secretion. The higher rate of secretion and lower overall
renal exposure to VCS may be associated with improved safety when
compared to more diffuse distribution and greater renal retention
of CSA and TAC.
Following is the complete guide to Aurinia’s presentations at
ACR 2023:
ACR 2023 Oral and Poster
Presentations:
Title: Comparison of
Dual-immunosuppressive Therapy with a Voclosporin-based,
Triple-immunosuppressive Regimen for Lupus Nephritis in the ALMS
and AURORA 1 Studies Authors: Maria Dall’Era, Ernie
Yap, Matt Truman, Lucy Hodge, Neil Solomons Date: Sunday,
November 12, 2023 Time: 2:00 p.m. – 3:30 p.m. PT Oral
Session: Abstracts: SLE-Treatment I: Renal
Title: Selective Disposition of
Voclosporin, Cyclosporine, and Tacrolimus in Renal Tissue
Authors: Simon Zhou, Krishani Kumari Rajanayake, Miao He, Bo
Wen, Ankhbayar Lkhagva, Ernie Yap, Duxin Sun, Jennifer Cross, Kory
Engelke, Robert B. Huizinga Date: Sunday, November 12, 2023
Time: 9:00 a.m. – 11:00 a.m. PT Session:
SLE-Treatment Poster I
Title: Long-term Safety and
Efficacy of Voclosporin in Black Patients with Lupus Nephritis:
Results from the AURORA 1 and AURORA 2 Studies
Authors: Gabriel Contreras, Matt Baker, Lucy Hodge, Ernie
Yap Date: Monday, November 13, 2023 Time: 9:00 a.m. –
11:00 a.m. PT Session: SLE-Treatment Poster II
Title: Efficacy and Safety of
Voclosporin in Patients with Proteinuria > 2 G/g
Authors: Emily Littlejohn, Salem Almaani, Vanessa Birardi,
Ernie Yap, Christopher Collins Date: Tuesday, November 14,
2023 Time: 9:00 a.m. – 11:00 a.m. PT Session:
SLE-Treatment Poster III
Title: Paired Kidney Biopsies from
the AURORA 2 study of Voclosporin in Active Lupus Nephritis
Authors: Samir Parikh, Salem Almaani, Arnon Arazi, Huijuan
Song, Pearlly Yan, Estela Puchulu-Campanella, Clint Abner, Ernie
Yap, Krista Piper, Robert B. Huizinga, Henry Leher Date:
Tuesday, November 14, 2023 Time: 9:00 a.m. – 11:00 a.m. PT
Session: SLE-Treatment Poster III
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
INDICATION 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
- Dall’Era M. et al. Comparison of Dual-immunosuppressive Therapy
with a Voclosporin-based, Triple-immunosuppressive Regimen for
Lupus Nephritis in the ALMS and AURORA 1 Studies. Presented at the
American College of Rheumatology Convergence, 2023, in San Diego,
CA.
- Zhou S. et al. Selective Disposition of Voclosporin,
Cyclosporine, and Tacrolimus in Renal Tissue. Presented at the
American College of Rheumatology Convergence, 2023, in San Diego,
CA.
- Contreras G. et al. Long-term Safety and Efficacy of
Voclosporin in Black Patients with Lupus Nephritis: Results from
the AURORA 1 and AURORA 2 Studies. Presented at the American
College of Rheumatology Convergence, 2023, in San Diego, CA.
- Littlejohn E. et al. Efficacy and Safety of Voclosporin in
Patients with Proteinuria > 2 G/g. Presented at the American
College of Rheumatology Convergence, 2023, in San Diego, CA.
- Parikh S. et al. Paired Kidney Biopsies from the AURORA 2 study
of Voclosporin in Active Lupus Nephritis. Presented at the American
College of Rheumatology Convergence, 2023, in San Diego, CA.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231107509867/en/
Media Inquiries: Andrea Christopher, Corporate
Communications Director, Aurinia achristopher@auriniapharma.com
Investor Inquiries: ir@auriniapharma.com
Aurinia Pharmaceuticals (NASDAQ:AUPH)
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Aurinia Pharmaceuticals (NASDAQ:AUPH)
過去 株価チャート
から 11 2023 まで 11 2024
