- Japanese drugmaker Astellas on Monday became the latest large pharmaceutical company to buy its way into a burgeoning gene therapy field, announcing a $3 billion deal to buy the San Francisco-based biotech Audentes Therapeutics.
- Acquiring Audentes will give Astellas an experimental treatment for a rare neuromuscular disease, as well as an entry point into the increasingly competitive race to develop genetic medicines for Duchenne muscular dystrophy.
- Astellas' buyout bid could also help lift a sector that's been weighed down by investor concerns resulting in part from delays to Roche's proposed takeover of Luxturna maker Spark Therapeutics, which remains pending review by U.S. regulators.
Astellas is paying up to join the gene therapy race.
At $60 per share, the Japanese pharma's takeover offer is more than double the $28.61 at which shares in Audentes traded at Monday's market close — a multiple on par with Roche's bid for Spark but higher than the premium Novartis offered for AveXis, and Biogen for Nightstar Therapeutics.
Impressive clinical results, paired with the prospect of speedy development, have made gene therapies an attractive investment for larger drugmakers. And approvals for AveXis' Zolgensma (onasemonogene abeparvovec) and Spark's Luxturna (voretigene neparvovec) on data from only a few dozen patients indicates a FDA willing to clear new therapies on less information than usual, providing the benefit is clear enough.
Select gene therapy deals in 2019
|Acquirer||Company acquired||Focus||Deal value (millions)||Premium*|
|Pfizer||Vivet (15% stake)||Liver diseases||$51 (+$636 in milestones)||N/A|
|Vertex||Exonics||Duchenne muscular dystrophy||$245||N/A|
|Astellas||Audentes||XLMTM, muscular dystrophies||$3,000||110%|
*Over closing price the day preceding deal announcement SOURCE: Companies
For Astellas, its interest in Audentes appears linked as much to the options buying the biotech opens up as it is to the company's lead drug candidate.
Importantly, Audentes owns a sizable manufacturing plant capable of supporting clinical and commercial gene therapy production. Manufacturing the inactivated viruses used to deliver the one-time treatments has proved a bottleneck for the field, so acquiring capabilities could give Astellas a leg up in the future.
And Audentes this year secured a collaboration with Nationwide Children's Hospital in Ohio — a hotbed for gene therapy science — that gave the biotech several programs aimed at Duchenne muscular dystrophy and myotonic dystrophy type 1.
That work remains preclinical, however. Nearer term, Audentes offers Astellas a gene therapy candidate that could be submitted to regulators for approval as early as the middle of next year. Called AT132, the therapy is designed to treat x-linked myotubular myopathy, a rare and usually fatal neuromuscular disorder affecting infants and young boys.
Mutations in the MTM1 gene result in missing or dysfunctional myotubularin, a protein essential to skeletal muscle cell development. Without it, affected infants are extremely weak and often require ventilator assistance to breathe. Half of those diagnosed die in the first 18 months of life, according to estimates cited by Audentes.
AT132 proposes a genetic fix for the disease, delivering a functional copy of the MTM1 gene via a type of viral vector known as AAV8. Results from a Phase 1/2 study showed infants treated with the therapy were able to sit, stand and even walk. Importantly, the ten treated patients were able to significantly reduce their dependence on ventilatory support compared to two study participants who were used as a control.
Neuromuscular conditions like XLMTM and DMD require much higher doses of gene therapy than diseases of the eye, brain or liver, making Audentes manufacturing capacity a vital asset.
Audentes is also developing a therapy for Pompe disease, which, like DMD, is targeted by several other companies. A clinical-stage program in the ultra rare condition called Crigler-Najjar syndrome, however, appears to have been put on hold this year by Audentes.
Astellas said it will house Audentes in an independent subsidiary, and plans for the acquisition to form a foundation for a new research focus centered on genetic regulation. A statement on the deal seemed to hint more gene therapy partnerships could be forthcoming, or at least made possible by buying Audentes.
At $3 billion, Astellas' acquisition is the largest buyout of a gene therapy developer since Roche-Spark, as well as the largest in a run of deals brokered by the pharma, which is perhaps best known for its development of the prostate cancer drug Xtandi (enzalutamide).
Astellas' interest in Audenetes could ease some worries that would-be acquirers might put off dealmaking in gene therapy until the Federal Trade Commission reaches a decision in its review of Roche-Spark. Repeated delays have raised eyebrows among investors and analysts, who largely expected the deal to close rapidly.
"In light of the pending [Spark-Roche] transaction, some investors may find Astellas-[Audentes] as another potentially drawn-out and uncertain tie-up,' wrote Joseph Schwartz, an analyst at SVB Leerink, in a note to clients.
"However, our review of Astellas' product portfolio and R&D pipeline suggests minimal overlap with [Audentes]'s focus on neuromuscular diseases."
Schwartz and colleagues were able to identify only two drug candidates that could share a target with Audentes', potentially making a takeover from the much larger Astellas easier to clear.