FDA OKs Phase 2 clinical trial of KYV-101 for progressive MS

The U.S. Food and Drug Administration (FDA) has cleared a Phase 2 clinical trial to test Kyverna Therapeutics‘ cell-based therapy candidate KYV-101 in people with treatment-resistant progressive multiple sclerosis (MS).

Called KYSA-7 (NCT06138132), the open-label trial will enroll an estimated 12 patients with either primary progressive MS (PPMS) or secondary progressive MS (SPMS). Both of these forms of MS are characterized by symptoms that gradually worsen over time — unlike the more common disease type that’s marked by exacerbations, known as relapses.

Eligible participants must be adults, ages 18-55, and have not experienced any disease relapses or MRI activity in the last two years. As the trial is open-label, both researchers and participants will know the treatment being given.

“This approval is a critically necessary step that paves the way to enroll patients with treatment-refractory [resistant] progressive MS for whom there are no currently available treatment options in the KYSA-7 trial,” Bruce Cree, MD, PhD, clinical research director and professor of clinical neurology at the University of California, San Francisco, said in a company press release.

“This study offers participants a new hope for arresting relentless disability worsening and a potentially durable, treatment-free remission,” Cree added.

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The trial page lists a single study site at the Stanford Multiple Sclerosis Center, in California. The KYSA-7 study is expected to run through mid-2027.

MS is an autoimmune disease in which the immune system mistakenly attacks the body’s own cells in the brain and spinal cord. In progressive forms of the disease, symptoms steadily worsen and disability accumulates even in the absence of relapses or evidence of active inflammation on MRI scans.

There are few therapeutic options for progressive MS patients who aren’t experiencing relapses — known as non-active disease. Ocrevus (ocrelizumab) is the only approved treatment for people with PPMS, while mitoxantrone is the only cleared therapy for non-active SPMS in the U.S. Patients who are not responsive, or are refractory, to these treatments don’t have any other options, according to Kyverna.

KYV-101 aims to equip the immune system with the ability to target and eliminate antibody-producing B-cells, which are implicated in MS. Kyverna is developing it for a range of B-cell mediated conditions, including autoimmune diseases and certain types of cancer.

This type of treatment is called a CAR T-cell therapy, where a person’s own immune T-cells are isolated and engineered in the lab to contain a man-made receptor, or chimeric antigen receptor (CAR), designed to recognize the CD19 protein found on B-cells’ surfaces.

When the engineered T-cells are returned to the body, they’re equipped to specifically target and attack problematic B-cells, thereby resetting the immune system. It is believed that this will offer sustained disease remission for progressive MS patients with a single treatment.

KYV-101 also is designed to reduce certain side effects and improve tolerability relative to previously designed CAR T-cell therapies.

This very important study will answer whether CAR T-cell therapy offers a new treatment option for patients living with MS.

In a previous Phase 1/2 study (NCT02659943), KYV-101 was found to have anti-cancer effects in people with B-cell cancers, and was associated with a lower release of inflammatory molecules that drive certain side effects typically linked to CAR T-cell therapies.

The upcoming trial will involve progressive multiple sclerosis patients who have not experienced any MS relapses in the last two years and who are refractory to other MS treatments. Its main goal is to evaluate patients for any dose-limiting toxicities over a one-year period. Secondary goals relate to safety and clinical responses to treatment.

“This very important study will answer whether CAR T-cell therapy offers a new treatment option for patients living with MS,” said Manuel Friese, MD, professor of neurology at the University Medical Center Hamburg-Eppendorf, in Germany.

“This therapy holds the promise to alter the treatment paradigm of MS by fundamentally readjusting the immune system,” Friese added.

KYV-101 also is being evaluated in a Phase 2 study involving people with lupus nephritis, another type of autoimmune disease. Trials also are being planned for indications in systemic sclerosis and myasthenia gravis.