At first glance, Aurinia Pharmaceutical’s lupus nephritis drug voclosporin is nothing special. It’s a modified version of the widely-used immunosuppressant cyclosporine A, separated from its predecessor by a single amino acid.
We’ve been there many times before, most recently with Marathon Pharmaceuticals. A tweaked drug makes it to the market with marginal benefits and a major price tag.
What’s the deal?
Based on fresh data from its Phase 2b trial, released Wednesday, it seems voclosporin can produce profound and meaningful results. Enough to see Aurinia shares jump over 50 percent following the news.
At 48 weeks, lupus nephritis patients on the lower dose of voclosporin achieved a complete remission (CR) rate of 49 percent. Granted, the disease does naturally fluctuate in severity and both arms of the study were also taking the current standard of care mycophenolate mofetil (CellCept) and a tapered dose of steroids.
But amidst the noise, the CR rate was twice that achieved in the placebo arm (24%). A further 68 percent on the lower dose also achieved partial remission, compared with 48 percent in the control arm.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Strangely, patients on the higher dose of voclosporin had lower rates of complete remission (40%) at 48 weeks, though the group still significantly outperformed the placebo group and did slightly better than both the placebo and low dose arms when it came to partial remissions (72%).
For lupus nephritis, that’s great.
Up to 1.5 million Americans are believed to have some form of systemic lupus erythematosus (SLE), though it remains poorly understood and very difficult to treat. Lupus nephritis, a kidney complication, arises in approximately 60 percent of all patients.
Despite it high prevalence, there are very few drugs approved for the condition. GlaxoSmithKline’s Benlysta was the first lupus-specific drug to be approved in many decades, however, it offers only marginal efficacy.
To fill the void, many different therapies are used off-label, including steroids and immunosuppressants. The standard of care in Aurinia’s trial, CellCept, was designed and approved for transplant patients as a tool to prevent organ rejection.
Many of the drugs carry severe side effects and a number are incompatible with pregnancy, including methotrexate and CellCept. Some 70-90 percent of lupus patients are female and the disease commonly hits during childbearing years. Yet another reason an alternative treatment would be well-received.
As part of the Aurinia news release, Joseph Vassalotti, chief medical officer at the National Kidney Foundation noted the benefits of the drug as a replacement for less targeted therapies.
“Lupus nephritis carries with it life-threatening complications, including kidney failure. The treatment of the disease is challenging, and steroid side-effects are often difficult for patients to endure. The National Kidney Foundation supports the development of steroid-sparing treatment options, and we look forward to following the results of the Phase III trial,” Vassalotti said.
Voclosporin is a calcineurin inhibitor (CNI) that works by blocking interleukin-2 expression and T-cell mediated immune responses. These mechanisms help drive the disease, which can affect almost every organ in the body.
The same is true for cyclosporine, but due to side effects such as increased lipids and insulin resistance, it remains a last resort for patients already battling a complex illness. Aurinia believes voclosporin, with its nuanced modification, will prove to be more potent and have fewer off-target effects due to a reduced metabolic load.
There is a long way to go, but by focusing on the kidney complications, Aurinia has a decent shot at showing efficacy where many others have failed. Eli Lilly has overseen several Phase 3 flops in what is a highly heterogeneous disease.
Crucially, Aurinia’s latest data readout included positive signs of safety and tolerability. The Canadian company’s stock took a beating in August last year when it revealed 13 patients has died in the active arm of this same Phase 2 trial.
In a phone interview late last year, then-CEO Charles Rowland Jr., said the patient deaths reflected the severity of the disease and the poor healthcare infrastructure at many of its trial sites in Sri Lanka and Bangladesh.
Aurinia expects to commence its AURORA Phase 3 trial in Q2 of 2017.
Photo: Dmitrii Guzhanin, Getty Images
