Late-stage trial testing KYV-101 seeking adults with hard-to-treat gMG
If results are positive, developer will seek regulatory approval of cell therapy
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- An ongoing clinical trial testing KYV-101, a CAR T-cell therapy for generalized myasthenia gravis, is now seeking gMG patients for its Phase 3 portion.
- Specifically, the trial is enrolling adults whose gMG has been unresponsive to other treatments.
- Positive results from this study may lead to submissions for regulatory approval for the experimental therapy.
A late-stage clinical trial testing KYV-101, a CAR T-cell therapy for adults with hard-to-treat generalized myasthenia gravis (gMG), is still enrolling gMG patients to take part in its Phase 3 portion.
This portion of the Phase 2/3 KYSA-6 trial (NCT06193889) is open to people with gMG, ages 18 to 75, who have failed to achieve adequate control of symptoms despite available therapies.
Participants must be positive for self-reactive antibodies against acetylcholine receptor (AChR) or muscle specific kinase (MuSK), the two most common targets of gMG-driving antibodies. The first patient was enrolled in December and recruitment is now underway at more than a dozen sites on three continents: seven across the U.S., six in Germany, and one in Brazil.
“We continue to cement our leadership in autoimmune [CAR T-cell therapy] supported by our unique construct and a growing body of transformative clinical data that reinforces [KYV-101’s] differentiated profile,” Warner Biddle, CEO of Kyverna Therapeutics, the therapy’s developer, said in a company press release announcing business updates and 2025 financial results.
According to the company, Kyverna will present additional data from KYSA-6’s Phase 2 portion next month at the annual meeting of the American Academy of Neurology.
Should the results from the trial’s Phase 3 portion — whose design was aligned with the U.S. Food and Drug Administration (FDA) last year — be positive, those findings will be used as a basis to apply for regulatory approvals of KYV-101, per the company.
An autoimmune disease, gMG is marked by self-reactive antibodies that interfere with the communication between nerve and muscle cells. This leads to symptoms such as fatigue and muscle weakness.
The most common types of antibodies that drive MG target the AChR or MuSK proteins. Antibodies, including self-reactive antibodies, are produced by B-cells, a type of immune cell.
Cell therapy aims to reduce levels of MG-driving antibodies
KYV-101, also known as mivocabtagene autoleucel (miv-cel), is a CAR T-cell therapy that uses immune T-cells, which have the capacity to kill other cells, to specifically promote the death of B-cells. By decreasing levels of B-cells, the experimental therapy is expected to lower levels of MG-driving antibodies, ultimately easing gMG symptoms.
In CAR T-cell therapies, T-cells are collected from a patient and engineered in a lab to carry a human-made receptor protein, called CAR, that directs them against specific proteins at the surface of target cells.
In KYV-101, the CAR is designed to target CD19, a protein found on the surface of B-cells. The modified T-cells are then infused back into the patient so they can attack and destroy B-cells.
Prior to KYV-101 treatment, patients must undergo a process called lymphodepletion, in which they receive a combination of chemotherapies to wipe out their existing immune cells and make room for the therapeutic cells.
To date, the experimental therapy has received fast track and regenerative medicine advanced therapy designations in the U.S. and orphan drug designation in Europe. These statuses are meant to accelerate KYV-101’s clinical development and regulatory review.
Phase 3 portion testing KYV-101 against standard-of-care treatment
The KYSA-6 trial was originally designed as a Phase 2 study in which 20 adults with gMG received a single infusion of KYV-101. But following discussions with the FDA, the trial was later expanded to include a Phase 3 portion designed to test the therapy against standard-of-care therapies. That portion of the trial will involve an estimated 60 patients.
Data from the Phase 2 portion, reported last year, showed all 20 participants experienced clinically significant reductions in disease activity as measured by two standard assessments, the Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.
The therapy was overall tolerated well. The sole serious adverse event was low counts of certain immune cells in one participant, which Kyverna said was an expected side effect of the treatment regimen.
In KYSA-6’s Phase 3 portion, participants will be randomly assigned to receive either a single infusion of KYV-101 or their clinician’s choice of standard-of-care therapy. Patients will know which treatment they are receiving.
The main goals of this part of the study are to assess whether KYV-101 is significantly better than standard-of-care at easing disease severity as measured by changes in MG-ADL and QMG scores after six months.
Secondary goals will investigate changes in on other measures of disease severity, as well as the number of patients who experience prespecified levels of improvement on these measures.
After six months, participants given standard care may choose to receive KYV-101. Study participants will be followed for at least two years.
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