FDA lifts hold on Astellas’ Pompe gene therapy

The FDA has delivered some good news to Astellas’ troubled gene therapy unit, lifting a clinical hold on its Pompe disease candidate AT845 and clearing the way for dosing of patients to resume.

The US regulator placed a hold on clinical testing of the gene therapy last June, shortly after a serious case of peripheral sensory neuropathy was reported in the phase 1/2 FORTIS trial in late-onset Pompe disease (LOPD).

That came amid a string of setbacks in Astellas’ gene therapy programmes, including a clinical hold imposed after cases of liver toxicity and deaths were in a trial of its AT132 gene therapy candidate for rare disease X-linked myotubular myopathy (XLMTM), and the halt of three candidates for Duchenne muscular dystrophy (DMD).

The company said it is “working on completing the clinical and regulatory activities necessary to resume dosing in the FORTIS clinical trial” and is looking forward to “the continued development of AT845 as an important potential new treatment for adults living with LOPD.”

AT845 uses an adeno-associated virus (AAV) vector to deliver a functional copy of the GAA gene coding for the enzyme acid alpha-glucosidase that doesn’t work properly in LOPD.

The hope is that a one-shot, intravenous treatment with AT845 can lead to expression of a functional form of the enzyme in tissues affected by the disease, including skeletal and cardiac muscle, and do away with the need for patients to receive regular injections with recombinant enzyme replacement therapies (ERTs) like Sanofi’s Lumizyme (alglucosidase alfa).

Signs that Astellas remained confident in the programme came earlier this month, when the pharma group licensed a drug developed by Selecta Biosciences that will be used in combination with AT845 in a $350 million deal.

Selecta’s IgG protease drug IdeXork (Xork) will be used as a pre-treatment to overcome one of the key limitations to AAV-based gene therapies like AT845, namely that some patients have existing antibodies against the AAV vector that interfere with the treatment.

Meanwhile, Astellas has continued to invest in its gene therapy business with a series of investments, including the payment last October of $50 million for a 15% stake in US biotech Taysha, securing an option on clinical-stage, single-gene therapies for rare genetic diseases Rett syndrome and giant axonal neuropathy (GAN).

That came just a few months after the company entered into a $1.6 billion alliance with Dyno Therapeutics (back-ended with just $18 million upfront), as well as the $3 billion acquisition of Audentes Therapeutics in 2019, which was the foundation for its push into gene therapy.

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