Astellas to acquire gene therapy firm Audentes for $3 billion

Looking to jump fully into the gene therapy arena, Astellas Pharma has agreed to acquire the gene therapy firm Audentes Therapeutics for about $3 billion.

Audentes was founded by Matthew Patterson in San Francisco at the end of 2012. Today, the firm has gene therapy programs for four neuromuscular diseases, one of which it will submit to regulatory agencies for review in 2020. The firm also has its own gene therapy manufacturing suite. “That has turned out to be the single-most important decision we’ve made as a company,” Patterson told C&EN at a conference in June.

Astellas, one of Japan’s largest drug makers, says Audentes will operate as an independent subsidiary. The purchase is the latest in a growing list of gene therapy deals since April 2018, when Novartis announced it would acquire AveXis for $8.7 billion. Gene therapy M&A slowed this summer after Roche’s planned acquisition of Spark Therapeutics got held up by antitrust agencies in the US and UK. The agencies are scrutinizing the deal since Roche sells a hemophilia drug and Spark is developing a hemophilia gene therapy.

In a note to investors, SVB Leerink stock analyst Mani Foroohar writes that the Audentes deal “could signal a return to gene therapy M&A.”

Many gene therapy stocks are well off their highs, making it an attractive time for larger drug makers looking to get into the field. Christopher J. Raymond, a senior research analyst at Piper Jaffray, told clients after the deal was announced that “gene therapy-focused stocks are likely to see a decent rally today and going forward.”

Audentes uses adeno-associated viruses (AAVs) to deliver DNA, primarily to treat genetic neuromuscular diseases. Its lead program is for X-linked myotubular myopathy (XLMTM), a rare condition that weakens skeletal muscle, causes serious breathing problems, and often results in death during infancy or childhood.

At a conference in May, Audentes shared preliminary data from a Phase I/II clinical trial that used a gene therapy to treat XLMTM. The company showed a video of a nearly immobile boy who needed a ventilator to breathe. In a second video taken during a follow-up visit after treatment, the boy was smiling and bouncing. The breathtaking turnaround made some people in the audience tear up.

Audentes plans on submitting its XLMTM therapy for regulatory approval in the US and Europe in mid- to late-2020.

The firm also has preclinical gene therapy programs for Pompe disease, Duchenne muscular dystrophy, and myotonic dystrophy type 1. The gene therapies for XLMTM and Pompe both use AAVs to deliver a functional copy of a gene—by far the most common approach in gene therapy. The muscular dystrophy gene therapies, however, use AAVs to deliver genes encoding antisense molecules that cause exon-skipping, or RNA silencing.

Sarepta Therapeutics markets an antisense molecule for muscular dystrophy, but it must be given as regular injections. And while other firms are developing gene replacement approaches for muscular dystrophy, Audentes stands out for developing a one-time antisense gene therapy delivered with AAV.

All of the firm’s programs use a variant of AAV called AAV8 that is a popular choice among companies developing neuromuscular gene therapies. Audentes licenses AAV8 from Regenxbio, a company cofounded by University of Pennsylvania scientist James Wilson.

Wilson has spoken out about the dangers of high doses of AAVs that are required for getting enough of the therapy into muscles. In January 2018 he resigned from the scientific advisory board of Solid Biosciences, a company developing a high-dose AAV9-based gene therapy for muscular dystrophy.

In March 2018, the US Food and Drug Administration put Solid’s lead therapy on hold after one of three patients was hospitalized with an immune system reaction following a dose of 50 trillion viruses per kg of body weight. FDA eventually lifted the hold, and Solid resumed testing a dose of 200 trillion viruses per kg in three additional patients. One of those boys was hospitalized for a severe immune reaction, and as of last month the trial is on hold again.

So far, Audentes has tested its therapy for XLMTM at a dose of 300 trillion viruses per kg. The company says it hasn’t observed any serious reactions.

Astellas clearly sees gene therapy as a risk worth taking. Its only previous foray into the field was the 2018 acquisition of a small British company called Quethera that is developing AAV gene therapies for glaucoma.