‘FDA-aligned’ trial of KYV-101 for MG likely to start enrolling this year
New Phase 3 study could support application for therapy's approval in US
A new Phase 3 clinical trial testing Kyverna Therapeutics’ cell therapy candidate KYV-101 in people with myasthenia gravis (MG) — a study the developer says “supports [a] clear and rapid path to [regulatory approval]” — is expected to start enrolling participants before the end of the year, according to a company update.
Kyverna is now conducting a clinical trial dubbed KYSA-6 (NCT06193889) to test its experimental therapy in MG patients. That study originally was conceived as an open-label Phase 2 trial, designed mainly to assess KYV-101’s safety in 20 adults with MG.
However, after discussions with the U.S. Food and Drug Administration (FDA), Kyverna has amended KYSA-6 to be a Phase 2/3 trial. The Phase 3 portion of the study is designed to be registrational, meaning that positive results could support a future application to the FDA seeking the approval of KYV-101, Kyverna noted in a company press release.
“As part of our efforts to accelerate our neuroimmunology franchise, we’re pleased to share today the details of our innovative, FDA-aligned Phase 3 trial in MG, which we believe offers an efficient and robust design and highlights KYV-101’s differentiated clinical profile,” said Warner Biddle, CEO of Kyverna. Per the release, “the company expects to initiate patient enrollment in the Phase 3 portion by year-end 2025.”
MG is caused by antibodies that interfere with the communication between nerve and muscle cells. Antibodies are immune proteins made by B-cells.
KYV-101 is an autologous CAR T-cell therapy — one using a patient’s own cells — that’s designed to deplete or lower the individual’s number of B-cells, thus reducing the levels of MG-driving antibodies.
The therapy involves first collecting T-cells, another kind of immune cell that can kill other cells, from a patient. The harvested T-cells are then engineered in a lab to be equipped with a chimeric antigen receptor (CAR), which directs them to specifically attack cells containing a B-cell protein called CD19. The modified T-cells are then infused back into the patient to attack and destroy B-cells.
Phase 3 portion of KYV-101 trial expected to enroll 60 MG patients
The Phase 3 portion of the KYSA-6 study testing KYV-101 is expected to enroll 60 adults with MG. To be eligible, patients must be ages 18 through 75 and positive for the most common types of MG-driving antibodies, which include those targeting the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). Patients must also be experiencing substantial disease symptoms and have failed to respond to at least one immunosuppressive therapy.
Participants in the Phase 3 study will be randomly assigned to receive a single infusion of KYV-101, or to continue receiving standard-of-care treatments, which may include corticosteroids, immunosuppressants, intravenous immunoglobulin therapy, plasma exchange, or complement inhibitors. The trial will be open-label, meaning that participants will know which treatment they are receiving.
The main goal of the Phase 3 trial is to show that KYV-101 is better than standard-of-care at improving the scores of two standardized measures of disease severity — the MG-Activities of Daily Living (MG-ADL) and the Quantitative MG (QMG) — after about six months. The study will also assess the therapy’s impact on other measures of disease severity, as well as the number of patients who experience prespecified levels of improvement on these measures.
Patients originally assigned to the placebo will also have the opportunity to receive KYV-101 after the first six months of the study.
Kyverna is expecting to report interim data from the Phase 2 portion of KYSA-6 later this year.
[Kyverna hopes KYV-101 can] fundamentally change the treatment paradigm in MG by providing durable … disease-free remission with a single dose.
In a webcast, the company shared the outcomes from the first three MG patients who received KYV-101 in a compassionate use program. Within a few months of treatment, all three reached a score of zero on the MG-ADL scale — essentially meaning they aren’t experiencing any MG symptoms at all. In all three patients, the MG-ADL score has remained at zero through the latest follow-up, more than a year after KYV-101 treatment, the company reported.
Biddle said Kyverna is “energized” in its development of KYV-101, a candidate for several immune system diseases, and hopes “to fundamentally change the treatment paradigm in MG by providing durable … disease-free remission with a single dose.”
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