Aurinia Presents Breadth of Data from AURORA Clinical Program Underscoring Value of LUPKYNISⓇ (voclosporin) for Patients with Lupus Nephritis at ACR 2023

• 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.

ROCKVILLE, Md. & EDMONTON, Alberta--(BUSINESS WIRE)-- 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

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.

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