Astellas makes gene therapy a core focus with $3bn Audentes buy

Astellas has made a foray into gene therapy with the acquisition of Audentes Therapeutics for $3bn, adding a late-stage candidate for a rare disease.

The deal comes shortly after Astellas reorganised its R&D operations, cutting programmes and staff to streamline its focus in areas like immuno-oncology, cell therapies in ophthalmology and mitochondria-targeting small-molecule drugs for neuromuscular diseases.

The Audentes deal adds gene therapy as a fifth platform technology while also bolstering Astellas neuromuscular programmes with AT132, a candidate for the treatment of X-linked myotubular myopathy (XLMTM) that could be ready for filing next year in the US and Europe.

XLMTM is a rare, genetic neuromuscular disorder that causes muscle weakness that ranges in severity from mild to life-threatening. In severe form of the disease – sadly the majority of those affected – the weakened muscles make breathing difficult and can lead to respiratory failure. It has a mortality rate of around 25% by the age of ten.

AT132 – an adeno-associated virus (AAV) based gene therapy that delivers the MTM1 gene deficient in XLMTM – is currently in a phase 1/2 trial called ASPIRO, which generated preliminary results from six patients in October.

According to Audentes, the therapy achieved significant and sustained improvements in neuromuscular function at two doses tested, with significant improvements in respiratory function. After 48 weeks, four of the six patients no longer had to use a ventilator device to support their breathing.

XLMTM only affects approximately one in 40,000 to 50,0000 newborn males, so it is a small indication, but gene therapies can command high prices and make solid revenues. For instance, the $2.1m Novartis charges for its spinal muscular atrophy therapy Zolgensma, now the most expensive drug in the world, helped the therapy to $160m in sales in its first full quarter on the market.

Meanwhile, Audentes has several other candidates in development, including therapies for Pompe disease, Duchenne muscular dystrophy and myotonic dystrophy that are being prepared for clinical testing.

Astellas says gene therapy will be a ‘key driver’ for the company in future, and it intends to let Audentes operate as an independent subsidiary, retaining its nimble nature while allowing it to tap into its parent’s scientific and development resources.

It’s not the first gene therapy deal the Japanese drugmaker has signed, but it is the largest. Last year, Astellas dipped its toe into the sector by licensing a preclinical-stage therapy for amyotrophic lateral sclerosis (ALS) from Japan’s Gene Therapy Research Institution.

Analysts say the price being paid for Audentes is on the high side – at an 110% premium on its share value ahead of the deal announcement. However it is in line with recent acquisitions of gene therapies by big pharma companies, such as Novartis’ $8.7bn AveXis takeover and Roche’s still-to-be-consummated purchase of Spark Therapeutics for $4.3bn.

One important element of the deal is that Audentes comes with a manufacturing facility already in place, which in itself is a significant asset given a current lack of production capacity for gene therapies.