Adaptimmune has won accelerated FDA approval for Tecelra (afami-cel), a treatment for metastatic or unresectable synovial sarcoma.
Tecelra’s approval comes with several firsts. It’s the first engineered cell therapy for a solid tumor, the first TCR-T therapy to enter the market, and the first new treatment in the indication in more than a decade.
It also is the initial approval for the 16-year-old company, which has attracted and lost partnerships with several pharma giants—including GSK, Astellas and most recently Roche—who were drawn to the potential of Adaptimmune’s unique engineered T-cell receptor (TCR) platform. It enables the engineering of T-cells to target and destroy many types of solid tumor cancers.
As the first engineered T-cell therapy for solid tumors, Tecelra marks a significant milestone, not only for the company but also for the advancement of cell therapy.
“It’s the first product where we use a lentiviral vector to insert our engineered T-cell receptor into the cell,” John Lunger, Adaptimmune’s chief patient supply officer, explained in an interview.
Iovance's Amtagvi, which was approved earlier this year, uses immune cells, called tumor-infiltrating lymphocytes (TILs), which are collected from a patient’s tumor, as opposed to CAR-T cell therapies, which are collected from a patient’s circulating blood.
“Ninety percent of cancer is solid tumors,” Lunger said. “The idea of a company like ourselves, going after solid tumors using cells, we’re finally getting to that place where we’re demonstrating this can actually work.”
The list price for the one-time therapy is $727,000. The addressable patient population in the US is roughly 400 per year, Lunger said.
Tecelra’s endorsement covers adults with advanced MAGE-A4+ synovial sarcoma of certain human leukocyte antigen (HLA) types who have received prior chemotherapy. Patients undergo companion diagnostic screening for their genetic HLA types and MAGE-4A expression.
Sarcomas are rare solid tumor cancers that develop in the bones and soft tissues including fat, muscle, nerves and blood vessels, which often strike young adults. Of the roughly 13,400 new soft tissue sarcomas diagnosed annually in the US, 5 to 10% are of the synovial type. The five-year survival rate is 20%, with most patients going through multiple lines of therapy, Adaptimmune said.
The approval is based on results of the SPEARHEAD-1 study of 44 patients, in which afami-cel provided a 43% overall response rate, with 4.5% seeing the disappearance of their cancer. For those who respond to Tecelra, the median treatment-free interval seen in the trial was 17 months.
“We’ve also seen for those responders about a 70% chance that they’re still alive after two years and that data is still developing,” Lunger said.
There were no treatment deaths in the study, though Tecelra can cause serious side effects including cytokine release syndrome and neurotoxicity.
“From the patient experience, when you compare what we have with a one-time therapy to the usual standard of care—which is chemotherapy, radiation and surgery—it’s extraordinary,” Lunger said.
As part of the accelerated approval, a confirmatory trial will be required.
Adaptimmune, which is based in Oxford, England, plans to have six to 10 designated treatment centers in operation by the end of this year, growing to 30 across the US by the end of 2025.
Adaptimmune went public in 2015 but found itself in dire straits in April when Genentech—in cost-cutting mode—exited a $3 billion partnership in which it was developing two allogenic T-cell therapies directed at up to five targets.
But seven weeks later, Galapagos stepped up, signing a $665 million deal for the rights to uza-cel, a MAGE-4A TCR T-cell therapy which Adaptimmune has in phase 2 for ovarian cancer. The Belgian biotech wants to take uza-cel into head and neck cancer and potentially other solid tumors.
The Galapagos deal, which includes $100 million up front, will help fund Adaptimmune’s launch of Tecelra.
Adaptimmune manufactures drug product for Tecelra in Philadelphia and farms viral vector production out to Miltenyi Biotec’s subsidiary Lentigen, which is based in Maryland. Adaptimmune handles all the manufacturing itself for uza-cel, performing viral vector production at one of its two sites in the UK.
“This approval represents a much-needed new option for people diagnosed with this sarcoma and an important milestone for the use of cell therapies in solid tumor cancers,,” Sandra D’Angelo, a sarcoma medical oncologist at Sloan Kettering Cancer Center, and the principal investigator of the SPEARHEAD trial, said.