In the summer of 2016, when Victoria, British Columbia-based Aurinia Pharmaceuticals Inc. offered phase IIb results with its calcineurin inhibitor voclosporin in lupus nephritis (LN), Wall Street ignored the otherwise-positive results and zeroed in on the trial’s death rate: 13 casualties across three arms of the 265-subject Aura-LV study.
Shares (NASDAQ:AUPH) were pummeled that day, closing at $1.81, down $2.28, or 55.7%, on volume more than 152 times the average, as investors were not persuaded by efficacy findings. What might have been a telltale factor – that 11 of the deaths took place in Asia, where access to health care is subpar in some regions – seemed to fall by the wayside.
But now Aurinia’s fortunes have turned around, with the company reporting data from the phase III experiment called Aurora, testing voclosporin in combination with mycophenolate and low-dose corticosteroids, in the treatment of LN. The study hit the primary as well as all prespecified hierarchical secondary endpoints, and voclosporin proved well-tolerated with no unexpected safety signals. Serious adverse events were reported in 20.8% of voclosporin patients vs. 21.3% in the control arm, Aurinia said. The stock ended Thursday at $15, up $6.61, or 79%.
Aurinia’s “concerted efforts in quality site selection and trial execution, particularly avoiding problematic sites in southeast Asia,” helped the outcome, noted SVB Leerink analyst Joseph Schwartz. He pointed to the low overall mortality rate (six patients), of which five were reported in the control group compared to a single death in the voclosporin group. “With a clear mortality advantage in favor of voclosporin treatment, we think the safety controversy will take a permanent backseat,” he said in a report.
The global, 357-patient Aurora study met its primary endpoint of renal response (RR) rates of 40.8% for voclosporin vs. 22.5% for the control (overall response 2.65; p < 0.001). All prespecified hierarchical secondary endpoints achieved statistical significance in favor of voclosporin, which included RR at 24 weeks, partial RR at 24 and 52 weeks, time to achieve urinary protein-to-creatinine ratio (UPCR) ≤ 0.5, and time to 50% reduction in UPCR. The robustness of the data was also supported by all prespecified subgroup analyses (age, sex, race, biopsy class, region, and prior mycophenolate mofetil [Cellcept, Roche Holding AG] use) favoring voclosporin.
Schwartz also cited Aurinia’s solid intellectual property position in LN, with composition of matter and method of use patents not expiring until 2027 and 2037, respectively. He modeled peak sales of about $1.6 billion by around 2029, before sales and market penetration begin to dip in the following year or so.
CEO Peter Greenleaf said during a conference call with investors that “the level of customer intimacy we intend to put together in the U.S. market in terms of our patient-care support services, etcetera, we hope will get us to a point where patients value our services commercially.” He added that voclosporin “isn't an immaterial drug to manufacture, and there are only a very few manufacturers who can produce all the steps in the process. Our goal would be to find the most reputable one and continue to set up a long-term agreement that would hopefully make it difficult for others to penetrate both on a full supply-chain side and commercially. But [we’ll have] more to come as we roll out our commercial strategy.”
An Aurinia cheerleader for some time, Leerink’s Schwartz in October pointed out that CEO Greenleaf “has been associated with significant shareholder value creation at other biopharma companies,” including Sucampo Pharmaceuticals Inc., of Rockville, Md., and Medimmune, the biologics arm of Cambridge, U.K.-based Astrazeneca plc. “Despite this promising set-up, in our view, Aurinia has been an underappreciated name for institutional investors,” he wrote in a report. “Part of this may be due to its Canadian domicile, and a lengthy development path that has been punctuated by controversial clinical data announcements for voclosporin.”
LN has proved a tough nut to crack for developers, although in systemic lupus erythematosus (SLE), Benlysta (belimumab, Glaxosmithkline plc), a monoclonal antibody against B-cell activating factors, gained FDA clearance during the first quarter of 2011. Threats to voclosporin in LN include Benlysta, currently in a phase III trial called Bliss-LN, with 448 subjects randomized to receive either the drug or placebo. All patients are on standard-of-care therapy (SOC) of steroids plus cyclophosphamide or steroids plus Cellcept). The primary endpoint is RR rates at 104 weeks, with a study completion data of next March.
Also in the LN mix is the anti-CD20 monoclonal antibody Gazyva (obinutuzumab), from Basel, Switzerland-based Roche Holding AG, which recently completed a randomized, double-blind, placebo-controlled phase II trial called Nobility that compared Gazyva plus SOC and placebo plus SOC in 125 LN patients. The primary endpoint was complete RR at 52 weeks. Key secondary endpoints included overall RR (complete or partial RR) and serologic markers of disease activity. In September, Roche said Gazyva plus SOC met primary and key secondary endpoints. Gazyva was first approved in November 2013 for chronic lymphocytic leukemia.
LN is a frequent complication in people with SLE, and occurs when lupus autoantibodies affect structures in the kidneys that filter waste, which causes kidney inflammation and may lead to blood in the urine, protein in the urine, high blood pressure, impaired kidney function or even kidney failure.