Voclosporin: A New Lupus Medication?

Voclosporin is a new immunosuppressant drug used to combat the symptoms of lupus nephritis. Aurinia, the maker of the medication, announced the submission of a FDA New Drug Application.

Voclosporin is a medication produced by Aurina Pharmaceuticals. It is similar to Cyclosporine, another calcineurin inhibitor that is sometimes used to treat lupus. Calcineurin inhibitors block calcineurin, an immune system messenger that activates T-cells, the pathogen-hunters of the body.

These cells are also responsible for the symptoms of lupus. Preventing their activation also prevents the symptoms of lupus, at the cost of leaving the body vulnerable to disease.

Voclosporin was also designed to be an improvement over cyclosporine. Although similar in its chemical structure, it binds to a different part of the calcineurin molecule. Specifically designed for kidney disease control, the medication is less likely than other calcineurin inhibitors to damage the podocytes in the kidneys. Podocytes are an important layers that filter the bloodstream.

In clinical studies, the medication less likely than a different competing medication, tacrolimus, to cause diabetes problems.

Research and Studies

Voclosporin was granted Fast Track designation by the FDA in 2016. In small exploratory studies (2013 case, with 33 subjects) Voclosporin appeared to be safe to administer to patients with severe renal impairment (kidney failure).

Further studies, such as the randomized, controlled, double-blind Phase 2 AURA-LV study (with 265 subjects) indicated that lower doses of Voclosporin, added to a normal medication regimen could lead to better kidney-related outcomes. The “normal medication regimen described included mycophenolate mofetil and corticosteroids)

The Phase 3 AURORA trial (or, the “Aurinia Renal Response in Active Lupus With Voclosporin”) was completed in 2019. Aurina announced that the trial “met its primary endpoint.” That is, the company considers it safe and effective.

The phase III study:

• Included 357 participants involved for 52-weeks
• Was a double blinded, randomly controlled trial (RCT) with an active control group
• Measured renal response rate after 52-weeks
  • UPCR (urine protein to creatinine ratio) of <= 0.5 mg/mg
  • eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%
  • Presence of sustained, low dose steroids (<= 10 mg Prednisone from week 44-52)
  • No administration of rescue medications
• Administered 23.7 mg BID (2x per day) of the medication

The announcement was made at the National Kidney Foundation 2020 Spring Clinical Meetings. You can see the presentation here.

You can read more about how clinical studies work, here.

The company announced it submitted a New Drug Application to the FDA for approval.

How Well does Voclosporin Work?

The chances of achieving renal response according to the phase III trial were 2.65x that of the control group. Significant improvements were found on the primary endpoint as well as secondary endpoints.

The latest data on Voclosporin is that it works well with the “gold standard” of Mycophenolate mofetil. It is more potent than other calcineurin inhibitors while not having as intense side effects. Studies, including the 6-month open label, randomized parallel PROMISE study, found that Voclosporin was more effective than tacrolimus. Tacrolimus is considered to be the standard of care among immunosuppressive medications.

The structure of Voclosporin is similar to Cyclosporin A. But, it is different in key places. These changes are responsible for its different effects and, potentially, better immune system suppression.

Chemical interactions are complicated, and we do not know everything about how they work in the body. However, when Voclosporin attaches to calcineurin, it changes the structure of calcineurin in a way that makes the messenger molecule less able to trigger T-cells.

Calcineurin inhibitors – including Voclosporin – are also used, with some success, for other inflammation conditions, including atopic dermatitis and plaque psoriasis. This could indicate some use of Voclosporin for cutaneous lupus or for systemic lupus or lupus nephritis with co-ocurring skin symptoms. You can read more about cutaneous symptoms of lupus, here.

Calcineurin Inhibitors and Side Effects of Voclosporin

As an immune suppressant drug, Voclosporin leaves the body vulnerable to infection. Calcineurin inhibitors also can also affect the ability of blood vessels to constrict or expand, increasing blood pressure.

Normally, this class of medication would not be recommended to reduce autoimmune symptoms in people who still have their damaged kidneys. This is because the side effect of high blood pressure can strain these already-stressed organs and damage them further.

However, Voclosporin works somewhat differently and the trials were specifically evaluated participants with lupus nephritis.

The AURA-LV study found higher rates of adverse effects when using the medication (including death in the low-dose Voclosporin group). However, the phase-3 AURORA trial did not have this increased mortality effect.

Phase 3 Trial

According to the larger and longer phase-3 AURORA study, Voclosporin was “well-tolerated,” and “no safety signals were observed.” By this, they mean that they did not see side effects that they felt were caused by the drug and not by the person’s lupus.

Adverse events were reported by 91% of study participants and by 88% of control participants (people who did not receive the medication). In both study groups, 4.5% people experienced serious adverse events related to the treatment.

Still, if you have high blood pressure and cardiovascular issues, your treatment team might be more reluctant to prescribe this new medication to you. Always speak with your lupus treatment team about medications and share your current treatments to minimize interaction effects.