Fresh from a US$52-million private placement, Aurinia Pharmaceuticals (TSX-V:AUP) hopes to treat its first lupus patient at the end of April in a Phase 2b clinical trial with its voclosporin immunosuppressant in combination with CellCept®, the standard of care for treating lupus nephritis (LN), the most severe form of lupus.
“We are now well capitalized to drive our clinical program,” CEO, Stephen Zaruby, says in an interview with BioTuesdays.com. “Our Phase 2b data should provide significant near-term value inflection.”
High-caliber U.S. institutional investors led the private placement, which will also be used to move Aurinia to the Toronto Stock Exchange and to obtain a NASDAQ listing within the next 12 months.
British Columbia-based Aurinia was created through a reverse merger with Isotechnika Pharma in September. Isotechnika originally developed voclosporin, a calcineurin inhibitor (CNI), for the treatment of kidney transplant rejection and several other indications, including psoriasis and uveitis, an eye condition. Voclosporin has been tested in more than 2,600 patients and is well characterized.
Mr. Zaruby says the merger was designed to recapture all the IP that Isotechnika had licensed to other companies and put it back into one company, Aurinia, as a stepping-stone to move voclosporin into a new indication, LN. There are no approved therapies for LN outside of Japan, which represents a significant unmet medical need and market opportunity.
“We have a substantially de-risked development pathway,” Mr. Zaruby contends, noting that the efficacy of a multi-targeted cocktail of CellCept and another CNI, tacrolimus, has been established in Asia. However, the use of tacrolimus has been associated with an increased risk of developing Type 1 diabetes and tremors.
“We believe voclosporin is potentially the best-in-class CNI, with patent protection until 2029,” he adds.
Lupus is an inflammatory disease that attacks the body’s organs. There are 500,000 to 1.5 million people in the U.S. with systemic lupus erythematosus (SLE), 40% to 70% of whom will develop LN, an inflammation of the kidneys. If left untreated or inadequately treated, LN can lead to end-stage renal disease and dialysis. Some 90% of patients suffering from lupus are women of childbearing age.
The core team behind Aurinia is from the former Aspreva Pharmaceuticals, which went on to conduct one of the largest LN studies in history, called the Aspreva Lupus Management Study (ALMS). The data from the study resulted in the emergence of CellCept as a new standard treatment for LN. Many of the clinical sites in the Aspreva study will be participating in Aurinia’s Phase 2b trial.
Although CellCept is the standard of care for LN, more than 90% of LN patients taking it fail to achieve complete remission. Additionally, recent chart reviews have indicated that even when treated with CellCept, the condition flares up in patients on average 1.7 times per year. “Patients are really sick at this point,” Mr. Zaruby points out.
“The immunology of lupus supports treating LN patients with a similar approach to transplant patients, using a multi-targeted therapy,” he adds.
According to Mr. Zaruby, CNIs in combination with CellCept are already considered standard of care for the prevention of solid organ transplantation rejection and more than 90% of transplant patients continue to receive life-long CNI therapy on top of CellCept. That’s the same multi-targeted approach that Aurinia is considering for the treatment of LN: CellCept plus CNI plus steroids.
In an abstract presented at the 2012 meeting of the American Society of Nephrology, researchers in China reported that they had achieved a 44% complete response rate with a cocktail containing CellCept and tacrolimus, as well as a 49% partial response rate.
Mr. Zaruby says Aurinia’s Phase 2b trial will seek to enroll 258 LN patients in approximately 20 countries. It will be a randomized, controlled, double-blinded study, comparing the efficacy of voclosporin against placebo in achieving remission in patients with active LN. All patients will receive CellCept and an oral corticosteroid as background therapy.
There will be a primary analysis to determine complete remission at week 24, with target disclosure in the fourth quarter of 2015, and secondary analyses of various biomarkers and markers of non-renal SLE at week 48, with a target disclosure in the third quarter of 2016.
The study is designed to demonstrate that voclosporin can induce a rapid and sustained reduction of proteinuria in the presence of extremely low steroid exposure.
“In this study, we hope to show that using voclosporin on top of the established standard of care can increase the frequency of remission, induce a more rapid remission and produce a more durable remission, enabling an overall reduction of steroid burden in these very sick patients” Mr. Zaruby says.
He thinks that regulators will require two adequate and well-controlled trials to consider voclosporin for marketing approval. “Depending on the results, we expect the Phase 2b to satisfy one of those trials,” he adds.
A Datamonitor SLE Pipeline study in 2010 pegged the lupus market to be approximately $3-billion by 2019 in the U.S. and Europe.
Aurinia estimates that there are more than 150,000 patients in the U.S. now receiving CellCept for the treatment of their lupus symptoms, of which some 70% have LN.
Mr. Zaruby says CellCept usage has been growing, especially since the drug went generic several years ago and the ALMS data were published in the Journal of the American Society of Nephrology and The New England Journal of Medicine.
In addition, CellCept has recently been incorporated into the American College of Rheumatology’s guidelines as a first-line immunosuppressive therapy for the treatment of LN.
“The greater the rate of CellCept use prior to any launch of voclosporin, the greater the opportunity,” Mr. Zaruby says. “We’re going to ask physicians to layer voclosporin on top of what they are already doing. This is a simple therapeutic proposition that should be well received once we reach market.”
According to Mr. Zaruby, there are a limited number of products in development for LN. “Voclosporin is the first and only small molecule in development. There’s competition in the space for sure, but we are unique in having a potential oral, flat-dosed treatment.”