First hATTR patient dosed in Phase 1/2a trial of gene-editing therapy
No treatment-related side effects reported two weeks after receiving YOLT-201
The first patient has been dosed in a China-based Phase 1/2a clinical trial testing YOLT-201, Yoltech Therapeutics’ one-time gene-editing therapy, in people with hereditary transthyretin amyloidosis (hATTR), a group of diseases that includes familial amyloid polyneuropathy (FAP).
Two weeks after receiving the investigational therapy, which was given as a single intravenous injection into the bloodstream, the patient was in good health and didn’t have any major treatment-related adverse events.
“The completion of the first patient dosing and safety assessment is a critical milestone in the clinical development of YOLT-201,” Yuxuan Wu, PhD, Yoltech’s founder and CEO, said in a company press release. “The early clinical trials have demonstrated excellent safety and efficacy for YOLT-201, and we believe it has the potential to transform the global clinical treatment landscape for ATTR diseases.”
Hereditary ATTR amyloidosis occurs due to inherited mutations in the TTR gene, which can be detected by genetic testing. The mutations cause the transthyretin protein to misfold and deposit as toxic clumps, which can damage tissues. In FAP, also called hATTR with polyneuropathy, those toxic clumps tend to build up in peripheral nerves that branch off from the spinal cord and extend to the body’s extremities, leading to widespread nerve damage.
When TTR mutations lead to toxic transthyretin clumps building up in the heart, the disease is called hATTR cardiomyopathy, or hATTR-CM. In it, the heart may beat abnormally or in an irregular pattern and may become enlarged, making it harder to pump blood to the body.
What is YOLT-201?
YOLT-201 uses a gene-editing toolkit that can modify the TTR gene so the transthyretin protein stops being produced. The editing toolkit is encased in tiny fat particles, called lipid nanoparticles, that head to the liver once injected into the bloodstream to deliver their cargo inside liver cells. This should prevent toxic transthyretin aggregates from building up, easing symptoms.
In a previously launched, investigator-initiated Phase 1 trial (NCT06082050) that’s testing YOLT-201 in up to 14 adults with ATTR-CM, ages 18-80, the therapy significantly reduced transthyretin levels without serious adverse events. The trial may still be recruiting at its single Chinese site.
The new Phase 1/2a trial, dubbed YT-YOLT-201-101 (CTR20241309), was cleared earlier this year by Chinese regulators. It’s evaluating YOLT-201’s safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy in up to 46 adults, ages 18-80 years, with FAP or hATTR-CM. Pharmacokinetics refers to a drug’s movement into, through, and out of the body, while pharmacodynamics refers to a drug’s effects on the body. Participants are being recruited at three sites in China.
In the study’s first, dose-escalation, part, increasing YOLT-201 doses are given to different groups of patients to identify the optimal dose for testing in a larger group in its dose-expansion part.
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