Since the approval of the monoclonal antibody Benlysta in 2011 (the ONLY medication ever designed specifically for lupus), scientists have been investing time and focus on new treatments for systemic lupus and lupus nephritis. This year has brought forth two FDA approvals out of this tireless research, with the market advancement of Saphnelo™ for SLE and Lupkynis™ for LN.
This blog will break down what each of these new therapies do, the benefits/side effects, and hopefully provide you with helpful information that you can take back to your doctor and have an open conversation about if these new medications may work for you in the future.
HOW LUPUS AFFECTS THE IMMUNE SYSTEM
In order for us to understand how these medications work, it is important to have a general knowledge of how our immune systems function, and malfunction if you have systemic lupus and/or lupus nephritis.
Lupus is defined as a chronic inflammatory disorder where your body's own immune system (your natural defense system) produces antibodies that attack your healthy cells by mistake. When this happens, it causes a process that may result in inflammation and tissue damage, and if it's not treated appropriately, may cause organ failure and death.
The immune system is constantly communicating between cells, informing each cell which cells are safe and which cells are not safe or are “invaders” like viruses, bacteria or foreign material. The cells that relay those messages are called interferons or IFN’s for short. There are different types of interferons, and they fall under the category of cells that doctors and scientists call “cytokines.” Cytokines are a variety of proteins secreted by the immune system that have an effect on other cells (interferons are one type of cytokines). They are not only what trigger your immune system to work - they are the first line of defense against infections!
They are the regulators, and if you are wondering why the word “cytokine” may sound familiar, here’s your answer. There is a growing body of data that suggests that a cytokine storm is associated with aggressive COVID-19. There is not an exact answer as to why this happens in some COVID cases, however; this flurry of cells going into attack mode causes inflammation in the lungs that leads to severe respiratory distress that can very quickly spill over into other systemic infections, causing worsening patient outcomes and even death.
Okay, sorry for that somber detail - now back to lupus. It has been discovered thanks to the Lupus Research Program, Lupus Research Alliance, the NIH and more research labs (like LFA) that this excessive type I interferon (cytokine) signature is found in up to 80% of adults with lupus and as many as 90% of children with the disease. This type of response is associated with the risk for more severe lupus manifestations (aka disease activity). So just like with the cytokine storm in COVID-19 that causes a flurry of inflammation in the lungs, these proteins can cause an inflammatory process in lupus, but in varying forms and severity, all over the body.
HOW SAPHNELO WORKS
Now that we have an understanding of the interferons and cytokines - let’s get to the good news.
As of August 2, 2021 The U.S. Food and Drug Administration (FDA) has approved Saphnelo™ (otherwise known as anifrolumab) as a treatment for adults with moderate to severe systemic lupus erythematosus who are receiving standard therapy (HCQ and corticosteroids). Saphnelo™ is now the third therapy for lupus to receive approval since 2011. As mentioned above, Benlysta was approved to treat SLE 2011, and later approved this year for the treatment of lupus nephritis. In January 2021, Lupkynis (voclosporin) was approved for lupus nephritis (we will get more into that later), and now Saphnelo™.
Developed by AstraZeneca, Saphnelo™ is a monthly 30 minute infusion that is the first therapy that specifically targets those overactive interferons (cytokines) that cause increased disease activity.
In clinical trials, Saphnelo™ showed benefits on overall lupus disease manifestations, including skin lupus, and joint involvement. It also displayed the ability to allow patients to taper down off steroids and patients saw lupus symptom improvement in as little as two months.
This is GREAT NEWS. However, with any new therapy there are things you need to know. First, Saphnelo™ has not been studied in combination with other biologic therapies, such as Benlysta, so if you are on Benlysta, you can’t take it (for now). It has not been tested on children with SLE and is also not for people who have severe active lupus nephritis or severe active central nervous system lupus.
The main side effects people experienced in the trials were cold-like symptoms. Additionally, a few patients came down with shingles; however, they were not serious enough to stop therapy and withdraw from the trial.
And the question that I am sure is on everyone's mind is how much is the new candy bar (sorry the name shouts CANDY BAR to me) gonna cost? Unfortunately, that is TBD. There’s no information out there yet on the clinical cost. However, AtraZeneca does have a co-pay assistance program for some of their medications, so here’s hoping it will work for this new therapy as well.
HOW LUPKYNIS WORKS
With lupus and other autoimmune diseases, the immune system is overactive or in “hyperdrive.” This immune response can lead to inflammation, and damage to organ tissue. When inflammation occurs in the kidneys, the outcome is a condition called lupus nephritis.
Lupus nephritis is one of the most serious disease complications of SLE, and can occur in 50-60% of patients with the disease. The treatments currently available for lupus nephritis include strong corticosteroids, anti-rejection medications, and toxic immunosuppressants.
Those that do not tolerate these treatments, often have to endure dialysis. For patients and doctors alike, this has simply not been enough. “For the last several years the community of lupus researchers in collaboration with the pharmaceutical industry have been engaged in finding more effective therapies for LN, but success has been difficult to achieve,” said Brad Rovin, MD, FASN, Director of Nephrology and Vice Chairman of Research for the Department of Internal Medicine at the Ohio State University Wexner Medical Center.
Enter Lupkynis™ (voclosporin) onto the scene. Lupkynis™ is an immunosuppressant medication that was originally developed in British Columbia by the scientists at Aurinia Pharmaceuticals. This therapy was created to help with near and long-term outcomes in patients with lupus nephritis when added to standard medication protocols. It works by inhibiting a specific protein that activates immune T-cells against the kidneys. By reducing the amount of chemical messengers traveling through an organ, voclosporin decreases inflammation in the kidneys and can halt further damage from occurring.
In a 2016 study, a total of 32.6% of individuals with active lupus nephritis that were given low-dose Lupkynis ™ along with standard-of-care lupus nephritis treatment achieved COMPLETE remission in 24 weeks (protein/creatinine ratio of 0.5 mg or less as well as normal renal function and GFR). High-dose also had significantly higher rates of partial remission at week 24 (69.7%) compared to placebo. "These preliminary results show great promise and could potentially change the current treatment paradigm for lupus nephritis," said chief investigator Mary Anne Dooley, MD, a rheumatologist in Chapel Hill, N.C. "The remission rates show a meaningful improvement over the current standard of care."
Besides the benefits it may provide to those living with lupus nephritis, it can also be helpful with treating another lupus overlap condition, noninfectious autoimmune uveitis, as well as skin conditions like psoriasis. It is also a PILL! No long infusion or needle pricks are necessary (except for your follow-up labs). Additionally, in some cases it can be used WITH Benlysta!
The most common side effects noted in clinical trials were gastrointestinal issues and an increased risk of infection.
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We hope this information is helpful to you in furthering discussions with your doctor about your treatment plan. As always, MTL will be the first to bring you the latest lupus news presented through the lenses of lupus patients.
Kelli (Casas) Roseta