Cell therapy weekly: positive progress made in autoimmune CAR-T trial
This week: A Phase II clinical trial assessing a CAR T-cell therapy for a neuromuscular autoimmune disease met its primary endpoint of delivering clinically meaningful improvements, while a Phase III trial evaluating a gene-editing-based therapy is temporally paused following a patient complication. Plus, clinical stage company Adverum Biotechnologies (CA, USA) is to be acquired by Eli Lilly and Company (IN, USA).
The news highlights:
- Positive Phase II interim data from autoimmune CAR-T therapy trial
- Phase III gene-editing trial paused
- Acquisition allows wAMD gene therapy to continue development
Positive Phase II interim data from autoimmune CAR-T therapy trial
Clinical-stage biopharmaceutical company Kyverna Therapeutics (CA, USA) announced positive interim data from the Phase II clinical trial of its CAR-T therapy KYV-101, indicated for generalized myasthenia gravis (gMG) – a neuromuscular autoimmune disease. gMG causes muscle weakness and fatigue, potentially leading to life-threatening symptoms, such as respiratory failure, and difficulty breathing and swallowing.
“With today’s results, we are setting a new standard across key clinical outcome measures for gMG, particularly in the depth and durability of response achieved with just a single dose of KYV-101,” said Warner Biddle, CEO of Kyverna Therapeutics. “…These compelling data build upon our previously reported compassionate use experience, further advancing our goal to deliver durable, drug-free, disease-free remission, and importantly, reinforce our confidence in the KYSA-6 Phase III trial design.”
The single-dose treatment met the primary endpoints with a 100% response rate in all six patients, delivering an 8-point improvement in daily living activities within 24 weeks and allowing patients to discontinue other immunosuppressive medications.
“Interim results showed that KYV-101 has the potential to deliver rapid, substantial and clinically meaningful improvements in [Myasthenia Gravis Activities of Daily Living], [Quantitative Myasthenia Gravis] and [Myasthenia Gravis Composite] scores for 100% of patients with a single dose, while also offering the potential for patients to become symptom-free,” said Naji Gehchan, Chief Medical and Development Officer of Kyverna Therapeutics. “With all patients exceeding the thresholds for our Phase III co-primary endpoints, we believe the data further validate the powering and overall design of our Phase III superiority trial. We look forward to initiating enrollment for the Phase III portion of the trial by the end of this year, as well as sharing updated data from the Phase II portion of the trial next year.”
Phase III gene-editing trial paused
Following the hospitalization of a patient from Intellia Therapeutics’ (MA, USA) Phase III trial for Nexiguran Ziclumeran (nex-z), the clinical-stage company has temporarily paused patient dosing and screening of its gene-editing-based therapy. Nex-z is a CRISPR/Cas9 gene-editing-based therapeutic designed to treat transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN). Nex-z is in Phase III clinical trials MAGNITUDE and MAGNITUDE-2 for the respective conditions.
A patient was dosed on 30 September 2025 in the MAGNITUDE trial for ATTR-CM. Less than a month later, the patient experienced Grade 4 liver transaminases and increased total bilirubin levels, leading to hospitalization on 24 October 2025, and requiring medical intervention.
“In line with our commitment to patient safety, we have taken immediate action to temporarily pause enrollment in MAGNITUDE and MAGNITUDE-2 as we investigate this recent event,” said Intellia President and CEO John Leonard. “As we focus on ensuring the health of this patient, we are also engaging with regulatory authorities and other stakeholders globally to develop a strategy to resume enrollment as soon as appropriate.”
To date, more than 650 patients with ATTR-CM are enrolled in the MAGNITUDE trial, and 47 patients with ATTR-PN are enrolled in MAGNITUDE-2. Approximately 450 of these patients are estimated to have been dosed with nex-z.
Acquisition allows wAMD gene therapy to continue development
Eli Lilly and Company is to acquire Adverum Biotechnologies along with its lead product candidate, Ixo-vec, an intravitreal gene therapy being developed for the treatment of wet age-related macular degeneration (wAMD). Ixo-vec is designed as a one-time treatment to deliver continuous intraocular aflibercept levels, aiming to reduce the burden of chronic anti-VEGF therapies and improve vision outcomes. The therapy is currently in the ARTEMIS Phase III trial, which has completed screening.
Ixo-vec has received Fast Track and Regenerative Medicine Advanced Therapy designations from the US Food and Drug Administration, PRIME designation from the European Medicines Agency and the Innovation Passport from the UK’s Medicine and Healthcare Products Regulatory Agency.
“…[Eli Lilly and Company’s] scientific depth and global reach offer the opportunity to accelerate our vision to deliver a transformative One and Done™ therapy that can potentially restore and preserve vision for millions of patients living with wAMD,” said Laurent Fischer, president and CEO of Adverum Biotechnologies. “My deepest appreciation goes out to the entire Adverum team for their expertise, creativity and commitment. We are also grateful to the investigators, patients and caregivers who have contributed to the success of Ixo-vec thus far.”
As part of the deal, Eli Lilly will pay Adverum’s shareholders US$3.56 in cash per share. Shareholders will also receive a contingent value right (CVR), which could provide up to an additional US$8.91 per share if certain milestones for Ixo-vec are met, bringing the total potential value to US$12.47 per share.