The FDA on Wednesday announced the approval of Novartis' CAR-T cell therapy Kymriah (tisagenlecleucel) for certain paediatric and young adult patients with acute lymphoblastic leukaemia (ALL), marking what the agency said is the first clearance of a gene therapy in the US. "We're entering a new frontier in medical innovation with the ability to reprogram a patient's own cells to attack a deadly cancer," commented FDA commissioner Scott Gottlieb.
Specifically, Novartis' therapy, formerly known as CTL019, was approved for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse. The decision comes after an FDA advisory panel in July unanimously backed approval of Kymriah for the treatment of patients aged three to 25 years with relapsed or refractory B-cell ALL. In updated results released in June from the Phase II ELIANA trial, Novartis said 83 percent of 63 evaluated patients in the study achieved complete remission or complete remission with incomplete blood count recovery within three months of infusion. Data also demonstrated relapse-free survival and probability of survival in a majority of patients at six months, the company added.
Novartis revealed Wednesday that a one-time single administration treatment with Kymriah will cost $475 000. However, the company also announced it is collaborating with the US Centers for Medicare and Medicaid Services "to make an outcomes-based approach available to allow for payment only when paediatric and young adult ALL patients respond to Kymriah by the end of the first month." The drugmaker added that "future potential indications would be reviewed for the most relevant outcomes-based approach."
Novartis indicated that it could have charged as much as $600 000 or $750 000 for Kymriah and the therapy would still have been cost-effective. Bill Hinshaw, head of the company's US oncology business, remarked "we're very comfortable" with the price, adding "we believe we are well within and below the range of standard of care in these models."
Kymriah's approval comes with a boxed warning about cytokine release syndrome (CRS) and neurological toxicities. The FDA said that as a result of these risks, it has created a risk evaluation and mitigation strategy for Kymriah, including a special certification for hospitals and clinics that administer the treatment to ensure staff are trained to recognise and manage CRS and neurological events.
Further, the agency also expanded approval for Roche's Actemra (tocilizumab) to include treatment of CAR-T-cell-induced severe or life-threatening CRS in patients two years of age or older. The agency indicated that in studies of patients treated with CAR-T cells, 69 percent had achieved complete resolution of CRS within two weeks following one or two doses of Actemra. Sandra Horning, Roche's head of global product development, noted that Actemra is the first "FDA-approved treatment to manage severe CRS associated with CAR-T cell therapy," and provides "an important tool to help manage this potentially life-threatening side effect."
Commenting on the Kymriah approval, Sanford C. Bernstein & Co. analyst Tim Anderson suggested that even with the $475 000 cost, the therapy is expected to generate limited revenue at first due to the relatively small number of eligible patients. According to Novartis, of the 3100 US patients aged 20 and younger who are diagnosed with ALL each year, about 600 would be considered candidates for treatment with Kymriah. Potential future uses of the therapy in additional cancers "could be much larger, but the offset to a larger population would be a lower price most likely," said Anderson, who expects the company to price the drug differently for other cancers.
Novartis indicated that it anticipates additional filings for Kymriah in the US and EU later this year, including for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma, with submissions in other markets expected in 2018. For additional analysis, see KOL Views Results: Inevitable approval of tisagenlecleucel-T an important first step to revolutionising blood cancer therapy, says leading oncologist.
Earlier this week, Gilead Sciences reached a deal to purchase Kite Pharma for $11.9 billion, gaining rights to the investigational CAR-T treatment axicabtagene ciloleucel. The FDA is expected to issue a final decision on axicabtagene ciloleucel for patients with refractory aggressive non-Hodgkin lymphoma by November 29 (for related analysis, see ViewPoints: With no pricing war on the horizon in CAR-T, the sky's the limit for Gilead and Novartis).
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