- Peter Marks, head of the Food and Drug Administration's Center for Biologics Evaluation and Research, said his top concern for gene therapy's future is manufacturing, and how companies will scale up production to match scientific advances.
- "When the cost of goods are very high, they help justify when people charge astronomical prices," Marks said in a recent interview with BioPharma Dive. "If we can help see cost of goods and ability to manufacture reproducibly improve, I think that'll be a big thing. That's something we're working on but something that keeps me up at night."
- The FDA has taken steps to keep pace with the field's rapid expansion. The agency aims to finalize six draft guidance documents by the end of 2019 related to gene therapy, including some that will address specific manufacturing issues, Marks said.
While it's far from the only challenge facing gene therapy, manufacturing is particularly critical for drugmakers developing the potentially one-time treatments.
Packing functional genes onto inactivated viruses to deliver into humans has brought new production problems to solve. Manufacturers used to small molecule drugs and biologics, meanwhile, have had to retool.
In response, contract development and manufacturing organizations have stepped up their dealmaking. In March, Thermo Fisher Scientific bought Brammer Bio for $1.7 billion, and Catalent purchased Paragon Bioservices the following month for $1.2 billion.
In explaining the decision to buy Brammer, Thermo Fisher's pharma services head said about 65% of total spending on gene therapy manufacturing is outsourced, as few companies have built their in-house capabilities yet.
Acquiring manufacturing capabilities and know-how has also factored into decisions by big pharma to enter the space, such as in Roche's $4.8 billion deal for Spark Therapeutics and Novartis' $8.7 billion buy of AveXis.
Sandy Macrae, CEO of Sangamo Therapeutics, another biotech working on experimental gene therapies, called manufacturing "a limited resource that everyone's competing over" in an interview last week with BioPharma Dive.
That scarcity and value led the biotech to build its own manufacturing facilities in addition to previous deals with CDMOs. Macrae said the site will allow Sangamo to produce therapies for commercialization on a smaller scale.
More involved manufacturing means gene therapy costs more to produce than the technologies before it. While Marks and others express concern such expenses will keep prices sky-high, it's not clear how much cost of goods dictates what drugmakers will charge.
"Cost of goods does not drive our thinking around pricing," said Dave Lennon, head of AveXis, in a May interview. "We believe in a value-based approach to pricing that is based on the condition we are treating and the value that the product brings to that condition."
Sangamo's Macrae, meanwhile, called the current level of costs for gene therapy products "manageable," noting the biotech took such costs into account when choosing which doses to focus on in testing.
"Sangamo is not just a science company, it's a company that is going to make products, and therefore we think about that and only go into things where the cost of goods is sensible," he said. "I think some of the other people are more enthusiastic and are not always factoring that in."
Which diseases drugmakers target matters, too. For conditions like the inherited form of blindness that Spark Therapeutics' Luxturna (voretigene neparvovec) treats, less viral vector is needed to deliver the therapy — meaning lower production costs.
Diseases like spinal muscular atrophy, Duchenne muscular dystrophy or hemophilia, though, require much more virus. Zolgensma (onasemonogene abeparvovec), for example, requires a dose many hundred times that of Luxturna.
As gene therapy makers become more ambitious, that could raise the manufacturing bar even more.
"I wouldn't call it unreasonable. I would call it unsustainable," Macrae added, on the high-dose vectors.