- Novartis is finding it harder than anticipated to commercially manufacture its cancer cell therapy Kymriah, acknowledging Wednesday that unspecified product variability has made it difficult to meet specifications in certain cases.
- Liz Barrett, head of Novartis Oncology, said the issues mainly involve CAR-T product for adult patients with lymphoma, rather than for children or young adults with adult lymphocytic leukemia, Kymriah's initial approval.
- Barrett emphasized that Novartis was still able to deliver a final dose of Kymriah to patients in the "majority of cases." Given the importance of manufacturing in CAR-T, however, the disclosure does raise some questions about how well Novartis can meet demand for the pricey cancer treatment.
Manufacturing is paramount in CAR-T, which involves the genetic engineering of immune cells extracted from a patient. Currently, patients treated with the cell therapy are often very sick, having failed other treatments. That shortens the window of time in which a CAR-T can be reinfused into a patient.
Novartis and rival Gilead aim to turn around their respective cell therapies in about two to three weeks from when a patient's cells are removed for manufacturing.
Issues in producing CAR-T therapies that meet specifications could prompt some concern, although Novartis says the problems it encountered haven't affected its ability to deliver Kymriah (tisagenlecleucel) to patients in most cases.
The apparent snag does raise questions, though, about Novartis' ability to quickly meet fresh demand for Kymriah following the therapy's recent approval in diffuse large B-cell lymphoma (DLBCL).
"We have seen some variability in our product specifications. This is something we're looking at now in DLBCL to make sure that we can continue to ramp-up the demand," Novartis CEO Vas Narasimhan said on a Wednesday earnings call. "We feel confident in the overall longer-term outlook for Kymriah."
It's not completely clear what issues Novartis is having, but Barrett indicated they involved CAR-T product being out of specification with Kymriah's label, which she characterized as more "stringent" than in clinical studies.
Per the prescribing information, dosing of Kymriah in adult DLBCL patients is higher than in ALL patients, as measured by the number of CAR-positive viable T cells.
Barrett also added that the manufacturing issue would not have any impact on clinical trials of Kymriah in earlier settings.
Since the U.S. approvals of Kymriah and Gilead's rival Yescarta (axicabtagene ciloleucel), sales have been fairly modest.
Novartis reported $16 million in sales of Kymriah during the second quarter, a notch below Wall Street's expectations of $20 million and less than half of the $40 million Yescarta posted in the first quarter. (Gilead has yet to report second quarter earnings.)
The Swiss pharma, though, expects sales will gradually climb as more centers become familiar with administering the complex treatment and as Kymriah's market expands from its new DLBCL label. On Wednesday's call, Narasimhan emphasized that Novartis sees Kymriah as a "five-year journey."