Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH) (Aurinia or the Company), a biopharmaceutical company committed to delivering therapeutics that change the course of autoimmune disease, today announced positive topline results from the AURORA 2 continuation study evaluating the long-term safety and tolerability of LUPKYNIS™ (voclosporin) for the treatment of adults with active lupus nephritis (LN), a serious complication in patients with systemic lupus erythematosus (SLE). In combination with background immunosuppressive therapy, LUPKYNIS is the first and only FDA-approved medicine with three years of pivotal trial results, including long-term safety data, within LN.
“Up to half of patients with systemic lupus erythematosus will develop lupus nephritis, that can result in severe and permanent damage to the kidneys and, in some cases, renal failure,” said Amit Saxena, M.D., assistant professor, department of medicine at NYU Langone Medical Center and an investigator in the AURORA 2 study. “These highly anticipated long-term results, of voclosporin in adult patients with LN, show consistent safety with the phase 3 AURORA 1 study and a benign impact on eGFR even after up to three years of treatment while maintaining the impressive reductions in proteinuria seen in AURORA 1.”
“We are pleased by the final results of the AURORA 2 continuation study evaluating LUPKYNIS for the treatment of lupus nephritis, which supports the long-term safety and tolerability for up to three years,” said Neil Solomons, M.D., Chief Medical Officer of Aurinia. “Furthermore, we observed that efficacy was maintained in combination with MMF and low-dose steroids.”
Highlights of topline results from AURORA 2:
- In the 116 subjects in the voclosporin-treated group who enrolled in AURORA 2, mean estimated glomerular filtration rate (eGFR) was stable over 36 months.
- Compared to the active control group, the voclosporin-treated group showed an increase from baseline eGFR at the end of the studies of +2.7 mL/min.
- The drug was well tolerated with no unexpected safety signals observed. There were comparable serious adverse events (SAEs) rates in both arms (19% voclosporin vs. 24% control).
- The active control group had a higher percentage of withdrawals compared to the voclosporin-treated group, 15.0% vs. 12.9% respectively.
- There were four deaths during AURORA 2 in the active control group, none in the voclosporin-treated group.
- The mean Urine Protein Creatinine Ratio (UPCR) was lower in the voclosporin-treated groups at all time points during the three years.
“Aurinia’s LN clinical program, including AURA-LV and both the AURORA trials, represents the largest successful LN program to date. The latest results, featuring consistent outcomes over three years, serve to reinforce LUPKYNIS as a safe and effective, important treatment option for patients living with lupus nephritis,” said Peter Greenleaf, President and CEO of Aurinia. “On behalf of Aurinia, I extend our deepest gratitude to the participants, their families, and the health care providers involved in these studies.”
Aurinia also announced the initiation of ENLIGHT-LN, a U.S.-based prospective, observational registry of adult patients with LN treated with LUPKYNIS. The registry is intended to support the interests of patients, clinicians, regulatory bodies, payers and industry by obtaining longitudinal data on LUPKYNIS. The Company aims to initiate approximately 75 sites across the U.S. Additional details regarding this registry will be provided in 2022.
Aurinia will host a conference call on Thursday, December 9 at 8:30 am EST to review these AURORA 2 topline results. The audio webcast can be accessed under "News/Events” through the “Investors” section of the Aurinia corporate website at www.auriniapharma.com or by dialing +1-877-407-9170 (Toll-free U.S. & Canada).
AURORA 2 Study Design
AURORA 2 (NCT03597464) is a Phase 3 randomized, double-blind, placebo-controlled clinical trial to assess the long-term safety and tolerability of voclosporin, in addition to MMF/steroids. Patients who completed 12 months of treatment in the Phase 3 AURORA 1 study were eligible to enroll in the AURORA 2 continuation study with the same randomized treatment of voclosporin at 23.7 mg twice daily or placebo, in combination with MMF at 1 g twice daily with low-dose oral steroids, for up to an additional 24 months. A total of 216 LN patients out of 357 who were enrolled in the AURORA 1 study continued into AURORA 2, with 116 patients in the voclosporin-treated group and 100 patients in the active control group. 90 and 78 patients, respectively, received 36 months of total treatment at the completion of the study. Results from the completed Phase 3 randomized, double-blind, placebo-controlled, multicenter AURORA 1 study (NCT03021499) were recently published in The Lancet.
About Lupus Nephritis
LN is a serious manifestation of SLE, a chronic and complex autoimmune disease. About 200,000-300,000 people live with SLE in the U.S. and approximately up to half of these individuals develop LN. If poorly controlled, LN can lead to permanent and irreversible tissue damage within the kidney, resulting in kidney failure. Black and Asian individuals with SLE are four times more likely to develop LN and individuals of Hispanic ancestry are approximately twice as likely to develop the disease when compared with Caucasian individuals. Black and Hispanic individuals with SLE also tend to develop LN earlier and have poorer outcomes when compared to Caucasian individuals.
LUPKYNIS is the first FDA-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.
Aurinia is a fully integrated biopharmaceutical company focused on delivering therapies to treat targeted patient populations that are impacted by serious diseases with a high unmet medical need. In January 2021, the Company introduced the first FDA-approved oral therapy indicated for the treatment of adult patients with active lupus nephritis (LN). Aurinia’s head office is in Victoria, British Columbia; its U.S. commercial hub is in Rockville, Maryland; and the Company focuses development efforts globally. Follow us on Twitter at @AuriniaPharma and on LinkedIn.
INDICATION AND IMPORTANT SAFETY INFORMATION
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.
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.
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.
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.