- Novartis' cancer cell therapy Kymriah didn't outperform standard treatment in a late-stage study of patients with relapsed or refractory lymphoma, a setback in the company's plans to expand the drug's use into earlier lines of care.
- Without providing details, the Swiss pharmaceutical giant announced Kymriah couldn't cut the risk of disease progression or death, the study's main goal, compared to treatment with chemotherapy and a stem cell transplant. Side effects were consistent with what's been observed with Kymriah, the company said in a statement. Novartis will present detailed findings at a future medical meeting.
- The disappointing results put Novartis behind top rivals Gilead and Bristol-Myers Squibb in the race to bring CAR-T treatments into earlier disease settings, a key way to help broaden their reach. Since June, both Gilead's Yescarta and Bristol Myers' Breyanzi have each succeeded in similar trials.
The commercial progress for so-called autologous CAR-T treatments, which genetically alter a patient's immune cells to find and kill cancers, has been slow to develop. The drugs are only approved for certain blood cancer patients who have essentially run out of options. Even then, they are hampered by logistical challenges such as a multi-week manufacturing and delivery process.
Though sales of Kymriah, for instance, grew 19% to $147 million last quarter, the "overall demand in the class has slowed down," said Susanne Schaffert, the president of Novartis' oncology division, on an earnings call. Revenues are well short of the blockbuster numbers the drugmaker initially envisioned.
The field's top developers — Novartis, Gilead and Bristol Myers Squibb — hope to change the narrative by bringing their treatments to earlier lines of care, a larger market opportunity. Each company has launched trials testing their treatments in second-line settings in lymphoma, where they're aiming to show CAR-T is better than chemotherapy and transplants at holding patients' disease in check.
Even if successful, the drugmakers will face challenges. While the combination of chemo and transplants often isn't curative and causes several side effects, CAR-T treatments are also associated with toxicities — most notably, neurological and immune-related problems — and are limited mostly to academic centers.
Nonetheless, prior to Novartis' announcement, the early returns had been encouraging. In June, for instance, Bristol Myers said treatment with its cell therapy Breyanzi resulted in a "clinically meaningful and highly statistically significant" improvement over standard care in patients with large B-cell lymphoma. Gilead immediately followed with a similar result for its treatment, Yescarta, along with plans to begin discussions with regulators.
Those two have now separated themselves from Novartis. The results disclosed by the drugmaker Tuesday come from the BELINDA trial, which tested Kymriah in 355 patients with aggressive B-cell non-Hodgkin lymphoma who either hadn't responded to first-line care or relapsed within a year. Novartis only revealed that Kymriah missed its primary goal, which was an improvement in the time to the first documented progression of disease, or death, at least 12 weeks after treatment. The company didn't say how Kymriah fared on secondary measures, such as the percentage of patients who responded or how long treatment effects appeared to last.
"The study investigators will work together with Novartis in the coming weeks and months to understand the factors that contributed to this outcome," said Michael Bishop, the chair of the study's steering committee and Director of the Hematopoietic Stem Cell Transplantation Program at University of Chicago Medicine, in a statement.
Kymriah is approved for acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Novartis plans to submit an application for use in follicular lymphoma later this year.