ART001 gene editor named orphan drug for ATTR amyloidosis
Accuredit Therapeutics cleared last year to begin clinical trial for FAP
The U.S. Food and Drug Administration (FDA) has granted orphan drug status to ART001, a gene editing candidate that Accuredit Therapeutics is developing as a one-time treatment for transthyretin (ATTR) amyloidosis, a group of diseases that includes familial amyloid polyneuropathy (FAP).
Such a designation supports developing possible treatment options for rare diseases that affect fewer than 200,000 people in the U.S. It offers benefits such as tax credits for clinical studies, exemptions from certain fees, and the possibility of seven years of market exclusivity if the treatment is approved.
“The orphan drug designation for ART001 by the FDA provides a solid foundation for its global development. Our team is excited to have the opportunity to develop ART001 as a safe, effective, and accessible treatment option for ATTR patients around the world,” Yongzhong Wang, PhD, Accuredit’s founder, chairman, and CEO, said in a company press release.
Last year, the FDA cleared the company to initiate a clinical trial of ART001 for FAP. In China, data from 10 adults with ATTR amyloidosis taking part in a clinical study (ChiCTR2400081216) showed a single infusion brought to nearly 0 the levels of disease-causing protein, while being safe and well tolerated.
Testing ART001
ATTR amyloidosis is caused by toxic deposits of misfolded TTR, a protein coded by the TTR gene. In hereditary ATTR amyloidosis, inherited mutations in TTR lead to these misfolds. The deposits, known as amyloid deposits, build up in various tissues of the body, damaging them and causing them to function abnormally.
In FAP, also called hereditary ATTR amyloidosis with polyneuropathy, amyloid deposits tend to build up in the peripheral nerves that extend from the spinal cord to the extremities, leading to symptoms of polyneuropathy (damage to multiple nerves). When these deposits build up in the heart muscle, they can cause ATTR amyloidosis with cardiomyopathy.
Given as a one-time infusion into the bloodstream, ART001 uses the CRISPR gene-editing toolkit to target TTR and edit its code, reducing the production of TTR. ART001 is carried in lipid nanoparticles, that is, small particles made up of fatty molecules, directly into liver cells, where most of the protein is produced. With less TTR, fewer amyloid deposits should build up, easing symptoms of both FAP and ATTR amyloidosis with cardiomyopathy.
In preclinical studies using lab-grown human liver cells, no off-target editing was observed that could cause ART001 to make unintended genetic changes, which could increase the risk of side effects, even at doses many times higher than its effective dose, according to the company.
The ongoing study, running at Suzhou Dushu Lake Hospital in China, is testing how safe and well tolerated ART001 is as a single infusion at ascending doses in adults with a genetic diagnosis of ATTR amyloidosis.
AccurEdit reported last year that 10 patients had been treated with ART001 at doses up to 1 mg/kg. After four weeks, circulating TTR was reduced by more than 90% with 1 mg/kg and by at least 80% with the 0.5 and 0.7 mg/kg doses. These reductions have remained stable for more than 15 months. ART001 appears safe, with no infusion-related reactions.
Two Phase 1/2a clinical studies — one in an estimated 13 adults FAP (ChiCTR2400090381) and the other in up to 12 adults with ATTR amyloidosis with cardiomyopathy (ChiCTR2400090369) — will further test ART001 at Peking Union Medical College Hospital in China.
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