Phase III clinical trial results have shown that remibrutinib relieves itching and hives in adults with chronic spontaneous urticaria (CSU). Pending careful review of the data by the FDA, experts say the drug may offer a new treatment option for CSU. Remibrutinib is an oral medication that comes in pill form. It also works in a different way than any other drugs now in use for CSU.
Up until now, doctors have mainly treated CSU with antihistamines. You may take them at high doses. Sometimes doctors will add drugs known as leukotriene modifiers. These drugs work by blocking leukotrienes, which are chemicals in your body that cause inflammation, swelling, and other symptoms. When those treatments aren't enough, you may try biologics, too. Biologics are made from monoclonal antibodies that help to block the autoimmune responses that drive CSU and many other conditions. For example, dupilumab (Dupixent) can help with the itch and hives that come with CSU. But biologics don't work for everyone. They also require regular shots. There's interest in finding new and potentially better ways to treat CSU, and that's where the story of remibrutinib's discovery and development comes in.
Before remibrutinib or any other new drug can be used to treat CSU, or even be tested in clinical trials involving people, it has to go through a lengthy process of development, testing, and review. The drug development process has many steps. Promising new compounds must be tested in the lab and in animals before they're ever given to small numbers of healthy people to see the most frequent side effects, and then in people with the condition to see if it's effective. Larger trials are used to see if new drugs work. New drugs often need to work better or more safely than any existing treatments before they can be approved and made available for use on patients. It takes years, and many drugs never make it all the way through. Learn more about how the development process has evolved for remibrutinib.
Step 1: Discovery and Development
Researchers first reported the discovery of remibrutinib, also known as LOU064, in February 2020. But the quest to find it began years before with the realization that a protein called Bruton tyrosine kinase, or BTK, was a promising target for treating CSU and other autoimmune conditions. The reason is that BTK is important for sending signals to immune cells called B cells that make antibodies. That includes the malfunctioning autoantibodies that attack your own tissues and drive autoimmune conditions, including CSU. Given the important role of those signals in autoimmunity, scientists thought drugs targeting BTK held promise for easing the itching and hives that come with CSU.
Remibrutinib isn't the first BTK inhibitor. The first drug ever approved in this class was called ibrutinib (Imbruvica). The FDA approved it for mantle cell lymphoma in 2013. The approval was later expanded to include chronic lymphocytic leukemia (CLL). Both conditions are cancers involving abnormal B cells. The medicines work by interfering with BTK and B-cell signaling.
While scientists recognized early on that BTK inhibitors might also treat allergic or autoimmune conditions, the first BTK inhibitors came with too many side effects and risks for their use outside of cancer. To use them for autoimmune conditions, researchers needed to find and develop BTK inhibitors that would work well and more safely. The key was to block BTK in a way that was stronger and more selective, with fewer unintended, or off-target, effects.
Step 2: Testing in the Lab
Remibrutinib's discovery and development involved lots of tinkering with the chemistry in the lab to find a compound that would bind BTK and not other kinases. Drugs that work in more specific ways generally come with fewer side effects and risks. Finding the right chemistry depended on detailed study of BTK's protein structure. Scientists had to understand exactly how the BTK protein works and how it can shape shift, or change its conformation.
The key to remibrutinib's selectivity is that it binds BTK when the protein is in its inactive form. The drug also binds BTK tightly without requiring the drug to stay at high levels. Studies in the lab showed that it strongly blocked BTK in the hoped-for way. The drug also remains stable in the bloodstream for hours. They found it could bind most BTK proteins – 94% – at a relatively low dose, too.
Those findings suggested remibrutinib might work well, and at a reasonable dose. But researchers needed to test it in animals. Further study in animals continued to look promising. Studies showed the drug gets into the body quickly. Any excess drug also clears from the body fast.
Studies in the lab of how remibrutinib acts in human blood and rats showed it was a strong BTK inhibitor. It could block BTK even when the drug wasn't present all the time. This was good news because it meant remibrutinib might work without requiring too much of the drug or constant exposure.
But how would it affect immune responses? Studies in rats found remibrutinib kept B cells from making antibodies. It also reduced inflammation in an animal model of a type of arthritis. The findings showed remibrutinib might be a safe and effective way to block BTK and autoantibodies for the treatment of inflammation and autoimmune diseases, including CSU. While researchers have continued to study other BTK inhibitors, they also moved remibrutinib on to the next step: clinical trials to test how safe it was and how well it worked in people.
Step 3: Testing in People
Studies in animals are important in drug development. But animals aren't people. To learn more about a drug's safety and how it might work, you have to test it in people. Clinical trials are carefully designed to answer essential questions. Early trials mostly help to determine needed doses and their safety. They might begin to show if a drug works.
Before starting a clinical trial, researchers and reviewers have to decide how many people they need in the study. They need to decide who qualifies for the trial and how long the trial will last. Many clinical trials include a control group of people who get a placebo in place of the active drug. Before a clinical trial can even start, drug developers submit an investigational new drug (IND) application to the FDA with data from animal studies along with information about the compound and their study plans. Clinical studies include three phases:
Phase I: Is it safe?
The goal of phase I trials is to consider the safety of a new drug candidate at different doses. They usually include relatively small numbers of healthy people and last a few months. According to the FDA, about 70% of drugs that enter a phase I trial make it to the next phase.
Results of the phase I trial of remibrutinib came out in 2021. People in the study included more than 90 healthy volunteers and 64 people with some signs of an autoimmune condition but no outward symptoms. The study showed doses of remibrutinib up to 600 milligrams cleared quickly. The drug didn't seem to build up in the body and wasn't affected by food.
At doses of 30 milligrams, it also blocked almost all BTK and reduced inflammatory immune cell activity. People who took remibrutinib tolerated it well. The researchers didn't see any signs that it was toxic at higher doses. It also looked like the drug might work in the blood and skin. The findings supported further testing of remibrutinib for possible use in multiple autoimmune conditions, including CSU, allergic asthma, and Sjogren's syndrome.
Phase II: Is it safe and effective?
Phase II trials include more people with a particular condition or disease. They usually last longer than phase I trials. The goal is to find out if a drug candidate works to treat a particular condition as hoped. Phase II trials also offer a first real look at any side effects. Most drugs tested in phase II trials don't make it to phase III.
Results of the first trial testing remibrutinib in people with CSU appeared in 2022. The trial included people with CSU whose symptoms weren't controlled well enough with antihistamines. The study tested six different doses over 12 weeks. Researchers looked for changes in hive activity over the course of the study and whether the drug was safe.
About 300 people with CSU enrolled in the study. The trial data showed that treatment reduced symptoms at every dose from the first week to the last. The drug didn't come with any serious side effects either. People taking remibrutinib had infections a little more often than those taking a placebo. Overall, the findings showed remibrutinib relieved symptoms of CSU well. It also worked rapidly without any serious safety concerns.
Phase III: Is it safe and effective in a study of more people?
Phase III trials include even more people. The goal is to see how well a treatment works in more people with a condition. Because phase III trials are larger and often last longer, they also can reveal side effects that may be less common.
Results of two phase III trials testing remibrutinib for CSU came out in March 2025. They're called REMIX-1 and REMIX-2. Both trials looked at how well the drug worked and how safely it treated CSU in people with symptoms despite them taking an antihistamine. People in the study got either the medicine or a placebo without knowing which they were taking. Those taking remibrutinib got 25 milligrams twice a day.
Each study included about 300 people who got the medicine and about 150 who got the placebo. The study showed those taking the medicine improved more over the course of 12 weeks than those taking a placebo pill. The number of side effects or adverse events was similar between the two groups. But those taking remibrutinib did get petechiae more often. Petechiae are tiny spots of blood under your skin. They're about the size of a pinpoint. Lots of things can cause petechiae, including certain medications. Overall, the findings showed remibrutinib significantly improves CSU symptoms, including itching and hives, after it was taken for 12 weeks without any serious side effects.
Step 4: Checking by Experts
After a successful phase III trial, drug developers submit a new drug application (NDA) to the FDA. It includes all the animal and trial data showing how the drug works and how it's made. Once the NDA is submitted, the FDA decides whether to review the drug for possible approval. They can ask for more studies, as needed. Once the FDA accepts a new drug for review, it usually gets reviewed within 10 months. Remibrutinib was approved to treat people with CSU on Sept. 30, 2025.
Step 5: Watching Over Time
Once a new drug is approved, the study isn't over. Newly approved drugs enter phase IV studies. Phase IV studies are also called post-marketing surveillance studies. Drug developers and doctors will continue to watch how remibrutinib works for people in the real world. They will collect observational data to make sure the drug works as well and as safely as it did in the carefully controlled clinical trials.
The Bottom Line
Remibrutinib has been approved by the FDA to treat CSU and will be available to treat CSU soon. That's based on phase III clinical trials showing the BTK inhibitor controls CSU symptoms in people who don't get relief from antihistamines. The drug also appears to be safe and well-tolerated. While it isn't yet clear if it works better than biologics, remibrutinib promises to offer an effective and fast oral option for easing the spontaneous itching and hives that come with CSU. With more study, this new medicine may find use for other conditions as well, with clinical trials now underway.
