“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” US Food and Drug Administration (FDA) commissioner Scott Gottlieb said yesterday as his Agency approved Novartis’s Kymriah – formerly known as CTL019 – for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).
Kymriah is the first product of its kind to be approved: a one-time treatment using a patient's own T cells to fight cancer, and the approval has been heralded as “historic” by both Novartis and cell & gene therapy advocacy groups.
“The FDA’s approval of Novartis’s CAR T-cell therapy Kymriah is a historic and monumental milestone for patients and the broader regenerative medicine sector. Great potential has become thrilling reality with the approval of what will likely be a cure for patients with B-cell acute lymphoblastic leukemia (ALL),” Janet Lambert, CEO of The Alliance for Regenerative Medicine (ARM).
Kymriah is made using an individual patient’s own T-cells, genetically modified to include a new gene that contains a chimeric antigen receptor (CAR) that directs the T-cells to target and kill leukemia cells.
According to Novartis spokeswoman Julie Masow, the autologous CAR T cell therapy is made at Novartis’ facility in Morris Plains, New Jersey.
Acquired from Provenge-maker Dendreon Corporation in late 2012, Novartis has since “made significant investments, and continue to invest, to support anticipated demand and meet the needs of patients” and recently announced it was upping the workforce at the site.
CAR-T cell manufacturing process
Leukapheresis – T cells within white blood cells extracted from patient through a blood filtration process. T cells are then cryopreserved and sent to the Morris Plains facility.
Reprogramming – T cells are genetically encoded to recognise cancer cells and other cells expressing a specific antigen, using an inactive viral vector (In Kymriah’s case this is made by London, UK-based Oxford BioMedica)
Expansion – the newly created CAR-T cells are expanded
Returned to patient – after tested for quality the product is released and shipped to the patient who has received lymphodepleting chemotherapy which aims to reduce the level of white blood cells and help the body accept the reprogrammed CAR‑T cells
Cell Infusion and cell death – after the CAR-T cells are delivered into the patient, they recognise cancer cells and other cells expressing a specific antigen, attach to them and initiate cell death
Novartis has set the price at $475,000 (€400,000) but said it could feasibly have charged a lot more.
“We carefully considered the appropriate price for Kymriah. We looked at many factors, including the medical and clinical value, the value to patients, the healthcare system and society, both in the near-term and long-term,” Masow told us.
She added Novartis sought input from external health economic experts and appraisals by review bodies like the UK’s NICE, as well as comparing the cost with allogenic stem cell transplants.
“These external assessments as well as our own health economic analysis of the value of Kymriah, all indicated that a cost effective price would be $600,000 to $750,000,” she said.
“Recognizing our responsibility to bring this innovative treatment to patients, we have set the price for Kymriah below that level at $475,000 for this one-time, single administration treatment. We believe this will support sustainability of the healthcare system and patient access while allowing a return for Novartis on our investment.”
However, patient advocacy group Patients For Affordable Drugs hit back at Novartis’ apparent pricing restraint, describing it instead as “excessive” in a statement.
“Novartis should not get credit for bringing a $475,000 drug to market and claiming they could have charged people a lot more,” said president David Mitchell.
He also asked whether Novartis would lower the price as the number of patients eligible for Kymriah expands, and, if approved overseas, if US patients will end up being charged more than citizens of other nations.