Manufacturing
Yet, beyond these technical hurdles, probably the most consistent issue encompasses manufacturers themselves. With so much money at stake, it makes sense that companies are reluctant to work together towards common goals, with the resultant cobweb of regulations often proving too much for industry minnows. “Companies in the CGT space are protective of their proprietary methods in manufacturing, by necessity,” says Courtney Silverthorn, associate vice president for research partnerships at the Foundation for the National Institutes of Health (FNIH). At the same time, however, Silverthorn is working to introduce collaboration to this most introverted of sectors. Bringing together some of the biggest pharmaceutical companies on earth, as well as major non-commercial interests like NIH, the new Bespoke Gene Therapy Consortium (BGTC) aims to regulate CGTs, giving scientists and regulators alike a common set of guidelines around new genetic treatments. More than that, the BGTC hopes to streamline manufacturing, making it easy for even small companies to get innovative products to market quickly. Nor are Silverthorn and her colleagues necessarily interested purely in genes and cells. On the contrary, the same principles of teamwork could soon be applied to other corners of medicine too, with equally dramatic consequences.
Lean, gene-fighting machines Though it’s usually described with that tight three- letter acronym, gene therapy in fact covers a bewildering array of treatments. One, for instance, replaces a disease-causing gene with a healthy copy. Another involves ‘deactivating’ a malicious gene, while a third introduces new or modified genes into a patient’s body, helping them combat a particular ailment. There’s similar variety when it comes to how scientists think about ‘vectors’ – the technical term for the vehicles by which therapeutic genes enter the body. That’s true, for example, of bacteria, which can be tweaked to carry genes into human tissue. Viruses can perform similar functions, while the plasmid DNA of certain microorganisms can be adapted too.
Combined with complementary research around cell therapy – and a market that’s predicted to see 52 distinct CGTs launch in 2024 alone – it’s no wonder experts are so exhilarated about what’s coming. “I am most excited about the impact of these medicines on the treatment of so many diseases, including those that have been difficult, or impossible, to treat,” is how Professor Kelvin Lee, director at the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), puts it. Yet, as he adds, the speed and scale of change can also cause problems, with both cell and gene
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therapies requiring “improved analytical tools to characterise the process and the product,” to say nothing of a bigger manufacturing workforce. Silverthorn highlights another problem with the contemporary CGT market: scalability. “At the high end,” she explains, “physical scale-up eventually becomes a limiting factor. At the low end, however, the traditional business model for drug development falls apart.” As Silverthorn concedes, this is true, to a certain extent, when fighting other rare diseases. Yet, because the regulatory and manufacturing costs for small molecule drugs are “substantially more achievable” than for CGTs, the latter have traditionally been too pricey for all but a handful of patients. Certainly, this point is bolstered by the numbers, with work by the Institute for Clinical and Economic Review finding that a single dose of a gene therapy has an average cost between $1m and $2m. The challenge of applying a small molecule drug development paradigm to CGT means that companies have typically been loathe to share techniques, with Silverthorn noting that because of high development costs, specialised manufacturing processes are guarded as closely as the delivery vectors themselves.
“I am most excited about the impact of these medicines on the treatment of so many diseases, including those that have been difficult, or impossible, to treat.”
Professor Kelvin Lee, director at NIIMBL Group therapies
Spend a few minutes studying the BGTC and it’s hard not to be impressed. This is especially true when you consider who’s involved. Bringing together 11 NIH institutes and centres, as well as commercial players as varied as Biogen, Novartis and Takeda, this is clearly a major undertaking. The same is true in terms of financing, with the BGTC altogether offering around $100m to CGT research. But beyond these headline figures, how exactly will the project support the manufacturing of new cell and gene therapies? For Silverthorn, it’s fundamentally a question of standardisation. Right now, there are so many different variables around testing, even before human trials can take place, that smaller firms (to say nothing of non- profits) find it hard to cope. But by developing what Silverthorn calls “a standard set” of quality and pre- clinical testing requirements, understood and accepted across the sector, she suggests “we can eliminate the cost and time of unnecessary testing and reduce the cost of manufacturing”. “The BGTC,” she continues, “has the highest number of private sector partners out of any of the Foundation’s current partnerships, which
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