Neil Solomons, MD, sits down to discuss his latest study, entitled “Aurinia Announces Publication of AURORA 1 Phase 3 Study Results with LUPKYNIS™ (voclosporin) in The Lancet,” which will be presented at EULAR 2021.
Rheumatology Network sat down with Neil Solomons, MD, to discuss his latest press release, entitled “Aurinia Announces Publication of AURORA 1 Phase 3 Study Results with LUPKYNIS™ (voclosporin) in The Lancet,” which will be presented at EULAR 2021. Solomons is the Chief Medical Officer at Aurinia Pharmaceuticals. We discuss the efficacy of voclosporin, the results of the research, as well as the clinical significance of the study.
Rheumatology Network: Hi, Dr Solomons. Thank you for joining me today. To begin, what sparked your interest in researching the efficacy of voclosporin in early disease intervention for patients with lupus nephritis?
Neil Solomons, MD: So, my team and I have been working on the development of drugs in lupus nephritis for almost 20 years now. And that started with a study called the ARMS trial, which was published in the New England Journal of Medicine in 2010. And that set the standard of care or treatment to lupus nephritis. The results were encouraging. But the only proportion of patients getting into a complete renal response was only about 20%, or even less in some cases. So myself and some of my fellow researchers, and some of the opinion leaders that I work with, felt there was an opportunity to do better than that, to choose new therapies, and to be able to reduce the amount of stories that patients are given and improve that complete renal response rates, which hopefully would lead to better long term outcomes in these patients. And we acquired a drug called voclosporin, or LUPKYNIS, and it was approved a few months ago for use in the US.
RN: Why do you believe lupus nephritis has been challenged with the lack of effective and safe treatment options?
NS: A couple of reasons. Obviously, this is a disease of young women of childbearing age. For the most part, 90% of subjects with lupus nephritis are women, most of those young, and the people of the patient population are very aware of the similar side effects of the drugs, for example, corticosteroids, and then want to reduce the amount of steroid that patients have. And of course, by reducing steroids, that can actually lead to a reduction in efficacy of the drug. So, the treatments that are given, we have to balance very carefully. The efficacy of a drug, how well a drug works with the safety of a drug, or the toxicities associated with that. And in addition, lupus nephritis or lupus, specifically, patients from a cocktail of drugs, are many of them doing slightly different things. It can be a difficult disease to actually monitor, it affects all parts of the body. We're specifically concentrating on the kidney manifestations, but there are other manifestations as well, such as skin and joint and things like that. And that also adds another layer of complexity.
RN: Can you tell me a little bit about the methods used to determine efficacy during the recent AURORA 1 and 2 studies?
NB: So, the main measure of advocacy is a measurement of proteinuria, which is protein in the urine. And that's assessed by taking out a urine sample. In the morning, void your urine sample, and measuring the amount of protein in the urine. What's been shown from previous work in the disease is that high levels of protein in the urine is associated with very high levels of disease activity. Also, reduction in protein in the urine is associated with a reduction activity. So, if you can give a drug that reduces the protein levels in the urine, or proteinuria, then you then it gives us an indication that the disease activity is reducing. So that's the main efficacy measure in our study.
RN: And what were the results of the studies?
NB: What's been shown is if you can get the urine proteinuria levels down to less than 0.5, that's approaching a normal level of proteinuria in the normal person with normal kidneys. And so that was the main goal of the trial was to get the protein urine levels down to 0.5. After a year of therapy, it's been shown from longer term studies that if you can do that, you increase the chances of better long term kidney outcome when you follow patients or prolong the time. So, if you can reduce the levels to 0.5, that's considered a good outcome. That was the primary endpoint of our trial, the proportion of patients on LUPKYNIS who achieved a 0.5 against the control arm.
RN: Were you surprised by the results of the study?
NS: No, I wasn't surprised. I mean, these types of drugs have been shown to be very effective in our phase 2 trial, but also, in some of the off-label work that's been done. I think the challenge we have, as with all clinical research is, is translating what we believe to be the case, what mechanistically is the case, what's been shown in small studies into bigger studies. And that's what we achieved.
RN: Were there any strengths or limitations that you'd like to expand upon?
NS: The main strengths of the AURORA trial is that pretty much all comers are included. So, we had patients who had very recent onset disease, patients who had disease are refractory to other therapies for patients who have very, very active disease, and patients who just had poorly treated disease as well. That's one of the strengths for a very broad range of patients who have come in. I think, amongst weaknesses, this is a clinical trial at a very rigid clinical trial setting. And one always has to be mindful when you present clinical trial data, what this actually means, in the clinic. Does this mirror what physicians do? And I think we tried to do that fairly closely. But I think treatment practices do vary across the United States. And so, I think there are probably some differences in the standard of care that physicians are required to perform.
RN: In your opinion, what is the clinical significance of this study?
NB: Clinical significance is that LUPKYNIS/voclosporin is effective in treating active lupus nephritis. And I think that the data are very, very clear. We've shown that in 2 consecutive clinical programs and we can do that with the safety profile as well.
RN: Is there anything else that you would like to add before we wrap up?
NS: You know, I think it's always a challenge during these clinical programs. Lupus nephritis is a devastating disease. And that affects a wide range of patients, specifically, patients from minority groups, as well as a company that we're very, very committed to helping these patients to get better outcomes in the disease. And I think that's probably the thing that drives me gets me up in the morning. And that brings me to work.
RN: Well, Dr. Solomons, thank you so much for taking the time to speak with me today. I really appreciate it.
NS: You're welcome.