New York, NY, November 9, 2020 — Results of clinical trials testing potential lupus treatments were highlighted at the American College of Rheumatology’s annual meeting ACR Convergence 2020. These studies include phase I trials, which test for side effects and a safe dosage; larger phase II trials, which test for effectiveness and further gauge safety; and large phase III trials, which confirm effectiveness, monitor side effects, compare it to commonly used treatments and collect information to allow the potential drug to be used safetly.
The LRA is proud to share results presented at the conference that were conducted, in part, through the Lupus Clinical Investigators Network (LuCIN) of Lupus Therapeutics, an affiliate of the Lupus Research Alliance (LRA). In addition, following summarizes results of key studies of interest to our lupus community looking for new treatment options:
A Cancer Drug Branches Out A drug that is also being tested against cancer reduces disease severity, according to a phase II, randomized trial sponsored by Bristol-Myers Squibb and conducted in part by LRA’s Lupus Clinical Investigators Network (LuCIN) managed by Lupus Therapeutics. The drug, iberdomide, works differently from other potential lupus treatments because it helps destroy two proteins that may spur immune cells to malfunction in lupus. The study tested iberdomide in 288 patients and found that 54% of the patients who got the highest dose of the drug showed significant improvement in their symptoms, versus 35% among patients who received a placebo.
BIIB059 and VIB7734 Promise to Rein In Rogue Cells The immune system molecules called type I interferons are one of the main culprits in lupus. Two drugs that target a major source of type I interferons decrease joint pain and ease skin symptoms, two independent trials showed.
In patients with lupus, immune cells called plasmacytoid dendritic cells that normally keep watch for bacteria and viruses begin releasing large amounts of type I interferons. Researchers have been testing a drug called BIIB059 that latches onto these destructive cells and curbs their release of type I interferons. In one new phase II, randomized study sponsored by Biogen, scientists measured the effects of the drug in patients with skin rashes and tender or painful joints. They discovered that after 24 weeks patients who received the drug had fewer sore joints. A second part of the study focused on cutaneous lupus, which affects the skin, and also found that BIIB059 was beneficial.
A separate phase I, randomized trial, sponsored by Viela Bio, tested a different drug, VIB7734, that reduces levels of type I interferons by killing plasmacytoid dendritic cells. Researchers gauged how well the drug worked in patients with cutaneous lupus and found that it decreased the amount of type I interferons in the blood and reduced skin inflammation. Viela Bio is now planning a larger study to further investigate the drug.
More Positive Results for Anifrolumab Anifrolumab also targets type I interferons. At the ACR meeting, researchers presented further evidence that the drug can be beneficial, and provided more detail on one of its side effects.
Three presentations combined results from the phase III Tulip-1 and Tulip-2 trials. One presentation suggested that the drug enables patients to reduce their steroid use while avoiding flares. A second analysis found that the drug produced long-term reductions in the severity of skin symptoms. Patients who received anifrolumab were most likely to show improvements in the skin, mucous membranes, skeleton, and muscles, the third study revealed. A fourth study also incorporated data from the phase II MUSE trial and found that patients treated with anifrolumab were more likely to develop shingles, although it usually only affected the skin.
Voclosporin Shows Kidney Benefits Voclosporin is a potential treatment for lupus nephritis, the kidney inflammation that affects about half of patients with lupus. The drug quashes potentially harmful T cells and prevents certain kidney cells from dying. Combined results from the phase II AURA-LV trial and the phase III AURORA 1 trial showed that voclosporin lessens the amount of protein in the urine of patients who are taking low doses of steroids, affirming that the drug reduces kidney damage.
New Uses for Belimumab and Obinutuzumab in Lupus Nephritis Belimumab made history in 2011 as the first new lupus drug approved in 50 years with four trials showing its effectiveness in SLE. Now, a phase III clinical trial has provided further support that the drug also protects against lupus nephritis . The two-year study found that patients who received belimumab had less kidney damage and their kidneys worked better while lowering the need for corticosteroids.
Obinutuzumab, a drug approved for treating leukemia and lymphoma, might curtail lupus nephritis symptoms by killing B cells. These cells cause damage in lupus by releasing proteins called antibodies that attack patients’ own cells and often their DNA. The latest results from a phase II clinical trial of obinutuzumab indicate that after two years, patients with lupus nephritis had less protein and blood in their urine, indicating less kidney damage. They also had fewer of the antibodies that target DNA, which may promote lupus nephritis.
Boosting Regulatory T Cells with NKTR-358 The immune system is hyperactive in lupus, possibly because cells that normally keep it in check, regulatory T cells, fail to perform their jobs or become scarce. The drug NKTR-358 increases the number of regulatory cells in patients with lupus by up to 12 times, a new clinical trial found. Patients who were treated with NKTR-358 also showed improvements in disease symptoms. Lupus Therapeutics is collaborating with Nektar Therapeutics and Eli Lilly and Company to further test the drug within LuCIN.
Stalling the Cell’s Garbage Disposal Cells trash worn-out or damaged proteins in a structure called the proteasome, and they often die if it isn’t working properly. Researchers predict that drugs which target the proteasome only in immune cells could be less toxic for patients than drugs that block the proteasome in many cell types.
Results presented of a small phase I clinical trial suggest that a potential drug, KZR-616, may target the proteasome found in immune cells. The trial found KZR-616 is safe and reduces the severity of lupus symptoms. For example, after 13 weeks of treatment patients had fewer painful joints, milder skin rashes, and less pain overall than before starting treatment. A new trial has started evaluating the drug in a larger group of patients.
Disappointing Results for Two Candidates A trial sponsored by EMD Serono and conducted in part by the clinical trials network of our affiliate Lupus Therapeutics tested an investigational drug evobrutinib. Researchers thought evobrutinib might provide benefits by thwarting B cells and stimulating helpful immune cells. However, the drug did not reduce the severity of symptoms.
Another study conducted in part through the LuCIN asked whether immediate-release or delayed-release versions of the steroid prednisone, a widely used treatment for inflammation, were more effective at reducing morning fatigue, a common complaint in lupus patients. The results showed that fatigue declined no matter when the patients took prednisone. However, patients who took the delayed-release form of prednisone at night did not feel less fatigue the next morning than did patients who waited to take the drug until they woke up; these results did not meet the study’s primary endpoint.
Promise for the Future The large number of positive late-stage trials suggests that more promising treatments for lupus could be coming in 2021. The LRA and LT are working with many of the pharmaceutical and biotechnology companies testing these potential treatments and will keep you updated on their status throughout the year.
