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CAR T-cell therapy makers are gaining a foothold in the autoimmune disease space, with companies such as Kyverna Therapeutics targeting rare diseases with limited treatment options.
After gaining some approvals in oncology, the race is on with several companies to bring this technology to autoimmune diseases. CRISPR Therapeutics and Novartisa treatment for lupus. CAR-T faces some challenges in cancer treatment, but researchers hope it may provide better results with fewer side effects for patients with autoimmune diseases.
“CAR-T therapy as a scientific approach is absolutely the right way to treat autoimmune disease – by making antibodies against yourself and eliminating the B cells that are causing the autoimmune disease,” said Shyam Dholakia, PhD, president of Kiberna’s rare disease business. “And using your own cells to solve the problem is the perfect target.”
But Kaiverna is also taking on a lesser known autoimmune disease, stiff-person syndrome, which causes muscles to become stiff and rigid, leading to painful cramps and other symptoms that are very rare and affect around 100,000 patients. 5,000 in the United States Currently, there is no treatment that targets the underlying disease, only symptomatic treatment. The most commonly used options are painkillers, anti-inflammatories, muscle relaxants and intravenous immunoglobulin, Dholakia said, and more options are needed for autoimmune diseases, he said.
“If you take infliximab for a long time, if you take kinase inhibitors for a long time, if you read the labels on all of these drugs that are approved for inflammation due to autoimmune diseases, the side effects are pretty bad,” he said.
The disease has been in the media’s spotlight since popular singer Celine Dion announced her diagnosis in 2022. Most recently, Dion How does the disease affect her? She talks about her life in a documentary released on Amazon Prime in June.
Kiberna is Phase 2 Kiberna has begun clinical trials for its CAR-T cell therapy KYV-101, aimed at treating stiff-person syndrome. The treatment has received fast track and regenerative medicine advanced therapy designations from the FDA. Kiberna’s lead candidate, KYV-101, is being tested under eight designations, including multiple sclerosis and myasthenia gravis. According to Doholakia, Kiberna aims to enroll 20 to 30 patients in the clinical trial for stiff-person syndrome.
“Currently, there is no CAR-T therapy approved for autoimmune disease by any company in the world, so we want to set a precedent that this is possible.”
Dr. Shyam Dholakia
Kiberna Rare Disease Business Unit Director
We interviewed Dholakia to learn more about the autoimmune CAR-T pipeline and what the company has learned from the oncology field.
This interview has been edited for clarity and style.
PHARMAVOICE: Why is Kyverna targeting stiff-person syndrome, even though the patient population is so small?
Dr. Shyam Doholakia: A lot of CAR-T therapies have been developed in oncology, but we’ve found that this approach has a lot of side effects. When you go through treatment and have cancer, your immune system becomes very fatigued. The normal cells in your body don’t work well and they become exhausted. If you look at the whole patient with an autoimmune disease, the rest of their immune system is normal except for the part that targets their own cells. So there’s an opportunity to get all the cells you need, just in much smaller quantities, but in a healthier state. We can now use that same kind of immune reset approach to make a big difference.
Currently, many diseases are treated with drugs aimed at treating symptoms, alleviating pain, improving muscle mobility, reducing inflammation, etc. However, the fundamental problem is that the antibodies produced in the body act against the body, and no one has seriously addressed this. We feel that this approach is long overdue.
Currently, there are no CAR-T therapies approved anywhere in the world for autoimmune diseases, so we want to set a precedent that this is possible.
Nowadays, commercialization plans are considered much earlier in the process, including clinical trial design. What are your thoughts on commercialization at this stage?
What’s great is we have the oncology playbook — we have several CAR-T therapies approved in oncology, we know the cost-effectiveness, we know the payer strategies — and that sets the stage for us to curate and optimize.
We also see similarities and synergies with what we’re doing in terms of our approach to resetting the immune system and significantly improving the condition of patients with chronic diseases. All of these ideas are working in parallel and are being incorporated into our protocols to gather data to not only support the approval of KYV-101 but also to make it available to patients.
What lessons have you learned from the oncology playbook that you are leveraging in drug development?
“Oncology patients are at a totally different starting point in terms of what they’re dealing with, the amount of side effects people experience in oncology are different, and the patient outcomes are different. Overall, compared to oncology patients, (our patients) are much healthier, apart from the autoimmune disease that we target. This gives us a great ability to provide a great deal of benefit to our patients and (minimize adverse outcomes).
Every patient who is on CAR-T therapy is being studied over time. What’s really important here is that we’ve done a lot of work to understand the right dose to get an effect without giving too much or too little. This fine-tuning is really important because it allows for a one-and-done approach.
What is the impact of Celine Dion’s public diagnosis?
Overall, this is a good thing for patients. This is a very diverse disease. Many patients give up on treatment while waiting for an official diagnosis because they don’t know how to seek help from the right healthcare provider. (Dion) is spreading awareness about this disease, which is a good thing.
What does the future hold for CAR-T in the autoimmune field?
“Rheumatoid arthritis used to be treated with gold injections, but now there are 56 drugs approved for it. But it’s still a multi-billion dollar opportunity because there are people who have progressive disease because these biologics don’t work. Science has finally advanced to the point where we can reset these and other autoimmune diseases that are primarily caused by errors in antibody production. I think this is an incredible opportunity. It will change medicine forever.”
Hopefully, in the long term, we can say that the incidence and prevalence of these diseases will not be as bad as they are today because CAR-T therapy will have a huge impact and help a lot of people.
