Shots:

• Volker spoke about the granting of marketing authorization by EC to treat adults with active lupus nephritis.The approval was based on the results of the P-III AURORA study 
• Volker also talked about the collaboration between Aurinia and Otsuka Pharmaceutical for the development and commercialization of LUPKYNIS
• The interview gives an understanding of how Aurinia is developing therapies for patient populations with serious diseases

Smriti: Tell us in detail about LUPKYNIS (MOA, ROA, formulations, etc.)

Volker Knappertz: LUPKYNIS^® (voclosporin) is the first U.S. FDA- and EC-approved oral medicine for the treatment of adult patients with active lupus nephritis (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. What makes LUPKYNIS different from previous CNIs is that therapeutic drug monitoring is not needed while patients are taking it. We also see other benefits when compared to older drugs in this category. For example, there was no observation of negative impact on metabolic parameters such as glucose and lipids as well as electrolyte handling by the kidneys (namely Mg++) in the voclosporin LN development program. All of these issues are known to be associated with older-generation CNIs which limited their clinical utility. The recommended starting dose of LUPKYNIS is three capsules twice daily with no requirement for therapeutic drug monitoring - which is unique among the CNI drug class. Also unique to LUPKYNIS is the patented eGFR pharmacodynamic dosing protocol on the FDA-approved label, which allows for tailored dose adjustments to address individual patient needs. Boxed Warning, warnings, and precautions for LUPKYNIS are consistent with those of other CNI-immunosuppressive treatments. 

Smriti: What are the results of the P-III AURORA 1 study and the AURORA 2 continuation?

Volker Knappertz: AURORA 1 results demonstrated that voclosporin helps to control LN and protect the kidneys from further damage without the use of high-dose steroids. At one year, voclosporin-based treatment regimen was more than twice as effective at achieving a complete renal response versus the standard care LN treatment regimen alone. Clinically and statistically significant improvements were seen in all pre-planned secondary endpoints, including time to renal response, partial response, and improvements in subjects’ urinary protein-to-creatinine ratios compared to standard care alone. This treatment benefit with voclosporin was observed across diverse patient subpopulations in its LN development, regardless of age, sex, race, and ethnicity as well as disease severity at baseline. 

AURORA 2 continuation study results demonstrated that voclosporin was well tolerated with a similar safety profile to control and no unexpected safety signals. Reductions in proteinuria achieved in AURORA 1 were maintained and the mean UPCR was lower in the voclosporin-treated groups at all time points during AURORA 1 and AURORA 2 studies highlighting the durability of the treatment response of a voclosporin-based treatment regimen for up to 3 years.  There was also a significant difference in eGFR slope in favor of voclosporin (-0.2 mL/min/1.73 m²) compared to the standard of care arm (-5.4 mL/min/1.73 m²) suggesting that renal function was better preserved with the addition of voclosporin to standard care.

Integrated data from the AURA-LV and AURORA clinical trials represent the largest LN data set, longest follow-up among currently FDA-approved therapies, and fastest remission rates for the management of active lupus nephritis.  

Smriti: Can we talk about the sales of LUPKYNIS? Besides US & EU what other locations are approved and expected to be approved in the next 6mos?

Volker Knappertz: The net revenue for Q3 of 2022 was $55.8 million; including a $30.0 million milestone from Otsuka related to the EC-approval of LUPKYNIS. Aurinia’s net revenues primarily consisted of the milestone from Otsuka, coupled with an increase in product sales to the company’s two main customers for LUPKYNIS, which was driven predominantly by further penetration in the lupus nephritis market. There were approximately 1,354 patients on LUPKYNIS therapy on September 30, 2022, compared with 1,274 at June 30, 2022.

A marketing authorization application (MAA) for LUPKYNIS was submitted to the UK Medicines and Healthcare products Regulatory Agency and to the Swiss Agency for Therapeutic Products (Swissmedic). Both submissions are currently under review with the timing to be determined. 

Smriti: Tell us about your collaboration with Otsuka Pharmaceutical for the development and commercialization of LUPKYNIS.

Volker Knappertz: Aurinia and Otsuka entered a collaboration and licensing agreement in December 2020 for the development and commercialization of oral voclosporin in the EU, Japan, the United Kingdom, Russia, Switzerland, Norway, Belarus, Iceland, Liechtenstein, and Ukraine. The agreement leverages Otsuka’s well-recognized expertise in rare kidney diseases to underscore Aurinia’s commitment to expanding access to voclosporin for the treatment of LN. Working together, Aurinia and Otsuka have prepared and submitted an MAA to the European Medicines Agency (EMA), which was approved in September, and the companies are continuing to work together to bring LUPKYNIS to market in Otsuka’s other territories, with applications under review in the UK and Switzerland, and a Japanese NDA in preparation.

Smriti: As per the Aurinia pipeline, the Aurinia team is developing other formulations of voclosporin. Can you please tell us more about that? (i.e. is it under LCM strategy or something else?

Volker Knappertz: Voclosporin is currently under Lead ID & optimization for additional formulations. 

Smriti: What are the upcoming drugs in your pipeline?

Volker Knappertz: AUR200 is a recombinant Fc fusion protein designed to specifically block B-cell Activating Factor (BAFF), and A Proliferation-Inducing Ligand, known as APRIL. BAFF and APRIL play important roles in regulating B cell survival and differentiation and have been shown to play a prominent role in the pathogenesis of certain autoimmune and nephrology conditions.

AUR300 is a novel peptide therapeutic that modulates M2 macrophages (a type of white blood cell) via the macrophage mannose receptor CD206. Dysregulation of M2 macrophages drives fibrosis. Unlike AUR200 and VCS which target B-cells and T-cells activity of the adaptive immune response, AUR300 targets the innate part of the immune system specifically M2 macrophages. There is growing recognition that the innate immune system plays a more prominent role in autoimmune disease pathogenesis than may have been previously appreciated.  AUR300 acts to reduce M2 dysregulation and decrease inflammatory cytokines

and therefore may have significant clinical applications for autoimmune and fibrotic diseases.

Both of these programs are rooted in strong science and at the leading edge of approaches for the treatment of autoimmune, fibrotic, and kidney diseases. Significant research has been done to date in both BAFF/APRIL inhibition and macrophage modulation and the Aurinia team is confident both of these approaches offer high potential across multiple autoimmune diseases.

Smriti: AUR200 is BAFF/APRIL. So is Aurinia planning to assess this molecule in autoimmune nephrological disorders?

AUR200 is under development as a next-generation therapeutic for B cell-mediated diseases. 

Source: Ayushman Hospital and Health Services

About the Author:

Dr. Volker Knappertz is the Executive Vice President of Research & Development at Aurinia Pharmaceuticals. He leads the entirety of Aurinia’s R&D effort, including pre-clinical research and pharmacology, clinical development, patient safety, medical affairs, regulatory affairs, and all other R&D functions. Dr. Knappertz is a recognized leader in the drug development community and has achieved numerous INDs and product approvals. Dr. Knappertz received his magna cum laude doctorate and Medical Degree from Cologne University.
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