No safety concerns seen one month after dosing with KYV-101 for lupus
Phase 1 trial now testing Kyverna therapy for lupus nephritis
No signs of neurotoxicity were seen for 28 days after the first patient in a Phase 1 clinical trial was dosed with KYV-101, Kyverna Therapeutics’ investigational cell therapy for lupus nephritis, a lupus complication marked by kidney damage.
A standard 4-week post-infusion observation period in such clinical trials is required by regulators to ensure patient safety, given that cell therapies can trigger ICANS, or immune effector cell-associated neurotoxicity syndrome. This neurological complication, which can cause neurotoxic symptoms, has been seen within one month of treatment in other patient groups,
The ongoing, open-label Phase 1 trial (NCT05938725) — designed to evaluate the safety of escalating doses of KYV-101 — is recruiting nine to 12 patients at clinical sites across the U.S. Kyverna also has been given the green light to launch a similar Phase 1/2 trial in Germany.
“These findings — when confirmed by our ongoing trials in the U.S. and Europe — could bring new life-changing treatment options for patients living today with lupus, and allow them to be free from the burden of autoimmune disease,” Peter Maag, PhD, Kyverna’s CEO, said in an emailed statement to Lupus News Today.
“We find the post-infusion data very compelling, and expect even more data in the next months to support the safety and efficacy targets we have set for our CAR T cell treatment,” Maag said, adding, “For lupus warriors that had to compromise their aspirations in life with an unforgiving disease, these findings bring renewed hope in a potentially life-changing treatment option that can free them from the burden of the autoimmune disease.”
Toxicity a major safety concern with any new lupus therapy
Lupus nephritis is a serious complication of lupus. This autoimmune disease can affect multiple organs and tissues, including the skin, joints, kidneys, brain, heart, and lungs, resulting in a wide range of symptoms.
About 40% of adults with lupus eventually develop lupus nephritis, and about 60% of those individuals do not respond to approved therapies. As a result, up to 10% of patients with the kidney condition and 40% of those with diffuse lupus nephritis, the most severe form, ultimately develop kidney failure, requiring dialysis or a kidney transplant.
There is a growing need for therapies that can drive greater and more rapid reduction of disease activity in patients with lupus nephritis.
Autoimmune attacks in lupus are known to be driven by hyperactive B-cells — the immune cells that produce antibodies. This increased B-cell activity leads to the production of antibodies that cause damage and inflammation in various parts of the body.
KYV-101 is a CAR T-cell therapy that targets CD19, a protein found on the surface of B-cells, which is involved in various types of cancers and autoimmune diseases. This form of cell therapy involves modifying a patient’s own immune T-cells with a chimeric antigen receptor, or CAR, designed to recognize and eliminate disease-causing B-cells.
“There is a growing need for therapies that can drive greater and more rapid reduction of disease activity in patients with lupus nephritis,” Amber Podoll, MD, trial co-investigator and an associate professor at the University of Colorado Anschutz Medical Campus, said in a company press release.
“Cell-based therapies offer a potential new approach to very complex, and often challenging to treat, severe medical conditions,” Podoll said.
Lupus therapy KYV-101 awarded fast-track status by FDA
ICANS is a side effect associated with CAR T-cell therapy that can lead to neurotoxic symptoms, such as confusion, drowsiness, tremors, and communication difficulties. In rare cases, a slow heartbeat, high blood pressure, breathing difficulties, and coma can occur.
While most ICANS reactions happen within a few days of dosing, in about 10% of patients, delayed neurotoxicity can arise three to four weeks later.
In a now-completed Phase 1/2 study (NCT02659943), KYV-101 demonstrated anti-cancer effects in patients with B-cell cancers. In addition, the cell therapy significantly reduced the release of immune signaling proteins associated with the development of ICANS. Because the treatment is based on a patient’s own cells, CAR T-cells persisted for one month due to their reduced ability to evoke an immune response.
Kyverna expects to present data on more dosed patients at an upcoming rheumatology conference.
The company recently signed an agreement to use Verily Life Sciences’ Immune Profiler to identify biomarkers that measure responses to KYV-101. The therapy also was granted fast-track designation for lupus nephritis in the U.S.
“Patients today should know that lupus has a new enemy,” Maag said, adding, “We are very excited about how patients respond to our anti CD19 CAR T-cell treatment after the standard observation period, and expect more data to support our confidence in being able to offer a potentially curative therapy to lupus warriors.”