Beyond the discount retailers and chain coffee shops in Stevenage High Street stands a facility manufacturing the latest generation of an innovative, personalised cancer treatment.
From the heart of the English commuter town, UK biotech Autolus will process, manufacture and ship to the US a new Car-T cell therapy to treat the blood cancer acute lymphoblastic leukaemia (ALL), after it received the green light from the US Food and Drug Administration in November.
The first Car-T therapies were approved in 2017 and they remain one of the most personalised medicines in oncology, leading to long-term remission for some patients. They are made by taking immune system cells from an individual patient, re-engineering them to kill tumours more effectively and putting them back into that patient.
But despite high hopes for the drugs when they were first introduced, steep costs, complex supply chains and gruelling side effects mean they are used only after other treatments have failed, limiting sales to date. The combined six therapies on the market made $1.2bn in sales in the most recent quarter, according to Matt Phipps, an analyst at investment bank William Blair.
Current therapies involve potential side effects such as a strong reaction of the body against the reinserted Car-T cells, making them tricky to deliver and requiring close supervision of patients, including reserving intensive care unit beds.
Autolus’s drug, which will be marketed in the US as Aucatzyl, binds to cancer cells for a shorter time than existing therapies, a factor that the company believes contributes to lower side effects. But the drug still faces challenges familiar to other Car-T therapies.
The limited uptake of Car-T to date was “a reflection of the fact that this is a complex therapy. But it’s one that has a very high level of activity and creates remarkable outcomes”, said Christian Itin, the company’s chief executive.
Aucatzyl, which will compete directly with Tecartus produced by US pharmaceutical group Gilead, has the backing of Blackstone. The private equity company made a $250mn investment in 2021 that helped fund the development of the Stevenage site. Covid-19 vaccine maker BioNTech also took a $200mn equity stake this year.
According to FDA data on the new Autolus therapy, of 65 ALL patients evaluated in late-stage trials, 27 had a complete remission after three months. Tecartus led to complete remission for more than half of patients in trials, although the results are not directly comparable.
Karl Peggs, a scientist at University College London — from which Autolus was spun out in 2014 — and a small shareholder in the company, said the theory of the new treatment was that because it bound to cancerous cells for a shorter time, the immune response was more muted.
“It seems to deliver a therapy that looks to have a better toxicity profile than the drugs that are currently available,” he said.
Nicholas Galakatos, global head of life sciences at Blackstone, said initial Car-T therapies were highly powerful but had damaging side effects for patients. “The first generation was kind of a blunt force,” he said. “The second will be more refined.”
But despite its differences from existing drugs, Autolus’s product also has shortcomings similar to other Car-T cell treatments.
The drug is priced at $525,000 per infusion, making it more expensive than Gilead’s Tecartus at $424,000, and its supply chain is complex.
Defending the price, Chris Vann, chief operating officer of Autolus, said the drug could reduce the strain on healthcare systems because hospitals would not have to reserve intensive care beds in case patients had serious adverse reactions.
Itin said the company was working to avoid supply constraints that have affected other Car-T treatments.
To make the Autolus therapy, US patients’ cancer cells will be harvested, flown to the UK, modified at the company’s Stevenage site and then flown back for reinfusion.
Despite the complex logistics, Itin said the supply chain would be robust. The company will consider establishing a US manufacturing site depending on uptake.
Phipps said doctors would “want to make sure it’s reliably delivered and manufactured” before choosing it over other treatments. As many patients are treated with Car-T cell therapies as a last resort, “if you don’t get the therapy back in a two to three-week timeframe, you might lose the patient”.
At the drug’s manufacturing facility, the company is busy scaling up production. Scientists on site demonstrated how blood was infused into specialised machines, where the immune cells were re-engineered and harvested. Once the treatment has been made, it must then be quickly cooled to freezing temperatures before being transported back to the US.
According to FactSet data, annual sales are expected to rise from $50.2mn in 2025 to $972mn in 2030, outstripping the $550mn that the data provider expects Tecartus to make by the end of the decade.
Makers of Car-T cell therapies have begun to explore other disease areas, with Autolus among several companies pursuing early trials in autoimmune diseases. Early results in Germany have shown Car-T therapies could be used to treat lupus, a disease where the body attacks healthy tissue including the skin, lungs, heart and kidneys.
But until it can prove this potential, Autolus’s treatment will be reserved for the small number of ALL patients who have relapsed from current treatments, amounting to 3,000 people in the US and Europe, where it has not yet been approved.
That means the company is planning to stick for now with its Stevenage-centred supply chain. “At the stage they’re at currently, with a very focused population, I think that’s the right thing to do,” said Galakatos.
