REVIEW: LUPKYNIS (voclosporin capsule)

 Lupkynis (voclosporin): This immunosuppressant medication, approved in 2021, features a microemulsion formulation that improves oral bioavailability. It's used for preventing rejection in kidney transplant recipients. Its applicant holder is Aurinia Pharmaceuticals. Inc, and application number is N213716. It has one strength, and it is 7.9 mg. 

Orange Book Patents

Lupkynis is covered by 3 orange book patents - 7332472 (exp. in 2024), 10286036 (exp. in 2037) and 11622991 (exp. in 2037). 7332472 claims "A composition comprising an isomeric mixture of a cyclosporine analogue modified at the 1-amino acid residue with a 1,3-diene substituent, wherein the isomeric mixture comprises about 90% to about 95% of the E-isomer and about 10% to about 5% of the Z-isomer, wherein the isomers are the isomers E- and Z", see below:"

7332472 has another independent claim also about isomers.

10286036 claims a pharmacodynamic method to treat a proteinuric kidney disease which method comprises administering to a subject diagnosed with said disease a predetermined daily dosage of an effective amounts of voclosporin over a projected treatment period of at least 24 weeks, said pharmacodynamic method further comprising: (a) assessing the estimated Glomerular Filtration Rate (eGFR) of said subject at at least a first time point and a second time point on different days of said treatment period, and (b) (i) if the eGFR of said subject decreases by more than a target % in the range of 20-45% to below a predetermined value in the range of 50-90 ml/min/1.73 m² between said first and second time points, reducing the daily dosage by increment(s) of 7.9 mg BID or stopping the administering of voclosporin to said subject; (ii) if the eGFR of said subject decreases by less than said target % between said first and second time points, continuing administering the same predetermined daily dosage of voclosporin to said subject.

11622991 claims a method of treating lupus nephritis (LN) in a subject, the method comprising:

a) selecting for treatment a subject having LN, the selecting comprising determining the subject's estimated Glomerular Filtration Rate (eGFR) at a first time point prior to initiating administering step b); b) administering to the subject voclosporin, mycophenolate mofetil (MMF), and corticosteroids, wherein the administering comprises administering the voclosporin at a starting dose of 23.7 mg administered orally twice daily (BID); c) assessing the subject's eGFR at a second time point after initiating the administering step b); and d) administering to the subject a reduced dose of 15.8 mg BID or 7.9 mg BID voclosporin to treat LN in the subject if, between the first and the second time points, the subject's eGFR decreases in the range of >20% to <30% below the subject's eGFR at the first time point to below 60 ml/min/1.73 m².

Sales

Aurinia issued a press release that Aurinia increased its net product revenue guidance to a range of $150 - $160 million for net product sales of LUPKYNIS. The guidance range was based on assumptions regarding PSF run rates, consistent conversion rates, time to convert, persistency, and pricing. (1)

LUPKNIS - API and Product Ingredients

LUPKYNIS (voclosporin) capsules is available for administration as soft gelatin capsules containing 7.9 mg voclosporin per capsule. Inactive ingredients include alcohol, Vitamin E polyethylene glycol succinate (NF), polysorbate 40 (NF), medium-chain triglycerides (NF), gelatin, sorbitol, glycerin, iron oxide yellow, iron oxide red, titanium dioxide, and water.

Voclosporin appears as white to off-white solid matter. At ambient temperature, voclosporin is freely soluble in acetone, acetonitrile, ethanol, and methanol, and practically insoluble in heptanes (USP). Voclosporin is practically insoluble (less than 0.1 g/L at 20ºC) in water and melts above 144ºC with decomposition.  

LUPKNIS - PK data

• With a twice daily dosing regimen, voclosporin achieves steady-state after 6 days and the accumulation is approximately 2-fold. 
• The median T max of voclosporin is 1.5 hours when administered on an empty stomach. 
• Co-administration of voclosporin with food decreased both the rate and extent of absorption: with meals, C max and AUC of voclosporin were reduced by 29% to 53% and 15% to 25%, respectively. 
• Protein binding of voclosporin is 97%. Voclosporin partitions extensively into red blood cells, and half-life is about 30 hours. 
• Voclosporin is predominantly metabolized by CYP3A4. CYP3A4 is a crucial enzyme in drug metabolism and detoxification, primarily resides in two key locations - liver and small intestine. 
• Following single oral administration of radiolabeled voclosporin 70 mg, 92.7% of the radioactivity was recovered in feces.

Adverse Reactions 

For details, please check with the product insert of LUPKNIS. 

Reference 

(1) Aurinia Pharmaceuticals Reports Second Quarter and Six Months 2023 Financial and Operational Results, Biospace.com, Aug 03, 2023.