As a top regulator at the Food and Drug Administration, Peter Marks isn’t responsible for weighing the cost of the treatments his teams review. But he is worried that some of the drug industry’s most promising medicines may not reach patients with uncommon diseases if companies can’t figure out how to sell them.
There are an estimated 7,000 rare diseases, many of which affect only small groups of people. Genetic medicines, including RNA-based drugs and gene replacement therapies, could offer a powerful way to treat, and potentially even cure, some of them. But for would-be developers, diseases affecting only a few dozen people might not represent a large enough market to justify the cost of developing and selling a new treatment.
“We're not going to find enough philanthropic groups to foot the bill for gene therapies for the hundreds upon hundreds of different diseases that need to be addressed,” said Marks, head of the FDA’s Center for Biologics Evaluation and Research, at a conference hosted by the Alliance for Regenerative Medicine on Wednesday.
“We're gonna have to find a way to make this commercially viable so that industry can find a way forward towards this."
According to Marks, commercial viability for a gene therapy means administering roughly 100 to 200 treatments a year, a threshold that could be difficult to clear in a single country for rare conditions like severe combined immunodeficiences or adrenoleukodystrophies.
“It has not escaped our attention at FDA that there have been some clouds on the horizon in gene therapy,” said Marks, noting instances when gene therapies were taken off the market or returned by their developers to the original academic researchers.
In Europe, for example, first GSK and then Orchard Therapeutics abandoned one of the first gene therapies approved there, a treatment called Strimvelis for a condition known as ADA-SCID. Only a few dozen patients were ever treated, and Orchard has also handed back rights to a successor treatment. More recently, Bluebird bio withdrew two gene therapies from the EU market after running into difficulties securing reimbursement in several European countries.
Bluebird recently won FDA approval for both of those therapies in the U.S. One, to be sold as Skysona at a cost of $3 million, is for an inherited condition known as CALD that affects about 50 boys each year. Bluebird has said it expects to treat around 10 each year.
In his remarks to the conference, known as the Meeting on the Mesa and attended by many in the cell and gene therapy field, Marks highlighted a few areas where the FDA could help ease hurdles for ultra-rare disease treatments.
The agency is currently putting together a “cookbook” for developing and manufacturing of bespoke gene therapies, which could help academic groups more easily transfer treatments they’re working on to industry. It’s also looking into how to use non-clinical and manufacturing data from one application to speed the review of others that share similar technology.
“There are certain pieces of gene therapies that are not like your typical small molecule drug, because they're reused repeatedly,” Marks said.
Automated manufacturing could be another solution to help lower the costs of production, which are significantly higher for cell and gene therapies than for other more established drug types.
The FDA is also hoping to get on the same page with other regulators so that developers could be more confident a product they gain approval for in one country would have a good chance of success in others.
“Some of [these problems] may relate to how we can make gene therapies for small populations more widely available,” Marks said. “What may be a tiny population in the U.S. becomes a reasonable sized population when you go globally.”