Astellas takes $170M hit as DMD gene therapy plan unravels in wake of preclinical data

Astellas’ gene therapy strategy is sinking deeper into the mire. Having reviewed the data on its Duchenne muscular dystrophy (DMD) gene therapies, the Japanese drugmaker has decided to scrap the candidates, triggering a $170 million impairment loss.

Working with Nationwide Children’s Hospital, Audentes Therapeutics—the gene therapy startup Astellas bought for $3 billion in 2019— generated preclinical evidence its AAV vector-encoding modified U7 small nuclear RNAs trigger improvements in muscle function. 

Armed with the data, Audentes began testing the gene therapy in 2020 in boys with a DMD-related gene mutation called exon 2 duplications. But after taking a look at the results of a preclinical study, Astellas has terminated development of the clinical-phase gene therapy, AT702, and a pair of earlier-stage candidates, AT751 and AT753, designed to treat DMD patients with genotypes amenable to exon 51 and exon 53 skipping. 

The termination will show up in Astellas' first-quarter results as a $170 million impairment loss. It adds to the $540 million the company suffered a year ago over the clinical hold on its lead gene therapy AT132 following deaths in a phase 2/3 trial.

Astellas is still feeling the pain of the troubled effort to develop AT132 for use in patients with the muscle disorder X-linked myotubular myopathy. In the statement to disclose the DMD termination, Astellas also revealed it will record a loss related to its reevaluation of the prospects of AT132.

Astellas voluntarily suspended screening and dosing of AT132 in September after a patient suffered liver problems at the lower, supposedly safer, dose. Weeks later, the FDA imposed a clinical hold as news of a fourth death emerged. Based on the delay—and a shift in thinking about the label that will be possible—Astellas will book an impairment loss.

The company grouped this loss with two other pipeline changes that add up to a further 50 billion Japanese yen ($390 million) financial hit for the previous quarter. The other two events are the termination of work on the DNA vaccine ASP2390 and the GITR agonistic antibody ASP1951. Both assets were in phase 1, ASP2390 in dust mite-induced allergic rhinitis and ASP1951 in cancer.