A drug originally used to boost the immune system is showing promise as a potential new treatment for lupus, joint Monash University and Peking University research published today shows. Lupus is an autoimmune disease, where the immune system attacks the body’s own organs and tissues.
An international team of scientists from Australia and China have, for the first time, shown in a study published in Nature Medicine, that a natural immune system protein called IL-2 can help restore balance to the overactive immune system of lupus patients. The drug could soon be rolled out for clinical trials in lupus treatment.
Monash Biomedicine Discovery Institute researcher, Dr Di Yu and Professor Zhanguo Li from Peking University People’s Hospital in China co-led the study.
Dr Yu said he hoped the drug could be approved as a lupus treatment within a handful of years.
“This drug, which can help the immune system fight against cancer, was approved in the 1990s but is not commonly used now. We’re now using this drug for a different purpose, based on our new knowledge of the immune system,” Dr Yu said.
“The amount we tested for treating lupus is much less than the dose used in treating cancers. We observed the treatment was safe and showed promising results, so there’s reason to believe formal trials could begin almost immediately,” he said.
Dr Yu said lupus could be a serious disease, and that it hadn’t been able to be treated in a very satisfactory way in the past.
IL-2 is a protein that regulates the activity of white blood cells, which are an important part of the immune system that protect the body against infections. In cancer therapy, patients are given large doses of IL-2 to stimulate their immune system but, paradoxically, the low dose IL-2 given to lupus sufferers in this study actually supressed the overactive part of their immune system that attacks their body. The research also showed the “self-checking” part of the immune system that prevents an overactive immune response, called regulatory T cells, increased after IL-2 treatment.
Professor Eric Morand, fellow Monash University researcher on the study and founder of the Asia Pacific Lupus Collaboration, said that in this study, IL-2 was given to people whose lupus wasn’t responding well to standard treatments.
“The real promise of this treatment is that it calms the hyperactive immune system through multiple mechanisms, which is very important as this new therapy may be effective for many patients,” Professor Morand said.
”As the drug has been on the market for some time for other diseases, it can be rapidly put into formal trials for lupus treatment right away.”
Learn more: Promising new treatment for lupus on the horizon
LupuzorTM may become the first specific and non-immunosuppressant therapy for lupus, a disabling autoimmune disease that is currently incurable.
Discovered by Sylviane Muller’s team in the CNRS Immunopathologie et Chimie Thérapeutique laboratory, in Strasbourg, this peptide is the subject of a CNRS patent (granted in 2009) and has already successfully completed phases I and II of its regulatory clinical trials, supervised by ImmuPharma-France. An international phase III pivotal trial1, also managed by this company, will begin in a few days’ time in the US when the first patient starts the treatment, before the trial is extended to Europe. Phase III is the last stage in the testing of a candidate drug, before it can be given market approval. The launch of phase III was the subject of a meeting involving around a hundred physicians on December 11-12, in Paris.
Lupus2 is a chronic autoimmune disease that affects more than five million people worldwide (around 30,000 in France), 90% of whom are women. It is characterized by the production of autoantibodies that attack different organs (skin, joints, vascular system, brain, kidneys) and cause inflammation, hence the broad range of possible symptoms: skin lesions, joint pain, thromboses, psychotic episodes, etc. To alleviate this disease with many causes, only palliative treatments are available at present, most of which are non-specific: corticosteroids and immunosuppressants, but they also weaken the immune system. Although they can stop autoimmune attacks, they also render patients highly susceptible to multiple infections. It was therefore urgent to develop a more targeted therapy.
The team led by Sylviane Muller, who received the 2015 CNRS Medal of Innovation3, developed a family of peptides (protein fragments) that can specifically correct dysfunction of the immune system4. One of these peptides, called P1405, proved capable of delaying the development of lupus in affected mice, while preserving their immune systems’ ability to fight infective agents. Since then, phase I and II clinical trials have been carried out6 by the company ImmuPharma-France, which holds an exclusive license for the patents that protect this family of peptides, all owned by the CNRS or filed as joint property. During phase II trials, the disease regressed in 62% of patients after 3 months of treatment: this is the best result ever to have been achieved for this pathology.
Following these successes, ImmuPharma-France launched its pivotal phase III trial. In the same way as during the phase IIb trials, the candidate drug will be administered under double-blind conditions once a month by the subcutaneous route, at a rate of 200 µg per injection, but the duration of treatment will be extended to a year, as opposed to 3 months previously. Two hundred patients will be included in this trial, spread across 45 centers (10 in the US and 35 in Europe7). The first patients will be recruited in the US by the end of 2015. In Europe, the trial should be starting in mid-January in the first centers, which include those in France. Recruitment should be completed by mid-2016 and the final results are anticipated at the end of 2017.
The first Investigators’ Meeting for the phase III trial took place on December 11 and 12 in Paris, and involved around a hundred American and European physicians.
Once this final phase of clinical trials is completed, and provided the results confirm those of phase IIb, LupuzorTM could be put on the market and subsequently play a central role in the treatment of patients with lupus.
According to preclinical findings, LupuzorTM may also be effective in other chronic autoimmune pathologies, such as Sjögren’s syndrome (dry eye syndrome) or Crohn’s disease (an autoimmune disease that causes chronic intestinal inflammation). Fundamental studies on these promising leads are now underway in Sylviane Muller’s laboratory.