FDA Expands Tisagenlecleucel’s Indication, Manufacturer Updates Price Tag

The U.S. Food and Drug Administration (FDA) has expanded the approval of tisagenlecleucel to include the treatment of patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. The indication includes diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, and DLCBL arising from follicular lymphoma.

The approval was based on results from the phase II JULIET trial, which were presented at the 2017 ASH Annual Meeting by Stephen J. Schuster, MD. “With this approval, physicians now have a meaningful therapeutic option that can achieve and maintain a sustained response without stem cell transplant along with a consistent safety profile,” Dr. Schuster said in a press release announcing the approval.

Among the 68 JULIET participants evaluable for efficacy, half responded to treatment, with 32 percent of patients achieving a complete response and 18 percent achieving a partial response. The median duration of response was not reached.

Cytokine release syndrome, a potentially fatal adverse event associated with CAR T-cell therapy, occurred in 23 percent of 106 patients treated with tisagenlecleucel. Eighteen percent of all infused patients experienced grade 3/4 neurologic events, including 11 percent who experienced encephalopathy. Neurotoxic AEs were managed with supportive care and there were no deaths attributed to neurologic events, the investigators reported.

In August 2017, tisagenlecleucel became the first FDA-approved CAR T-cell therapy when it received approval for the treatment of patients aged 25 years or younger with B-cell precursor acute lymphocytic leukemia (ALL) that is refractory or in second or later relapse. With the recent expanded approval, it is now the only CAR T-cell therapy approved for two distinct indications.

The proposed price of the therapy when used to treat lymphoma is $373,000, compared with $475,000 for the same therapy when used to treat ALL. This represents an example of controversial new “indication-based” pricing, in which drugs are priced differently based on the relative population frequency of approved indications, rather than distinct development or manufacturing costs or market forces. According to Harvard Kennedy School of Government Professor Amitabh Chandra, PhD, and Northwestern University Kellogg School of Management Professor Craig Garthwaite, PhD, “Indication-based pricing results in higher prices for patients who benefit the most, higher utilization by patients who benefit least, higher overall spending, and higher manufacturer profits.”

Sources: Novartis press release, May 1, 2018; Business Insider, May 7, 2018; Garthwaite C, Chandra A. The economics of indication-based drug pricing. N Engl J Med. 2017;377:103-6.

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