Recommendation for Novartis May Give New Hope For Some Cancer Patients

An advisory panel to the Food and Drug Administration voted 10-0 that the drug, tisagenlecleucel, should be approved to treat patients with relapsed B-cell acute lymphoblastic leukemia (ALL), the most common form of US childhood cancer.

The treatments involve extracting white blood cells or T-cells which defend the immune system, from cancer patients.

Treatment with a single dose of the resulting product had produced long remissions, and possibly cures, in scores of patients in studies who were facing death due to the failure of every other treatment.

Many of the FDA's advisers were effusive in their praise. Timothy Cripe, an oncologist at Nationwide Children's Hospital in Columbus, Ohio, called it one of the most exciting things he has seen in his lifetime.

Side effects, however, can be severe, and include spiking fever and crashing blood pressure. Eleven patients died, four from side effects and seven from their leukemia.

Novartis believes it can turn around a finished CAR-T product 22 days from receipt of leukapheresed material to final packing and shipping. For Emily and many other patients participating in the Novartis trials, the vehicle T therapy was an alternative, rather than just a bridge, to a bone marrow transplant, which carries a 30 percent survival rate.

About 6,000 people are diagnosed with ALL in the United States each year and about 60 percent are children, according to the American Cancer Society. Novartis is seeking approval to use the therapy on patients ages three to 25, particularly in patients who have failed to respond to standard treatments - something that occurs in over 600 people in the USA yearly.

Kite Pharmaceuticals has another CAR-T drug up for FDA priority review for the treatment of lymphoma. "You have to be a long-term survivor to experience [long-term] toxicity", said Bruce Roth of the Washington University School of Medicine in St. Louis, MO. That could leave just a few hundred patients who might be eligible for Novartis' therapy, casting doubt on whether the company can get an outsize return on what will be a substantial manufacturing investment.


But despite the financial promise, the commercial barriers are high for developers of CAR-T therapies. Last month, updated results from the phase 2 ELIANA trial showed that 83% of pediatric patients achieved complete remission (CR) or CR with incomplete blood count recovery within the first 3 months of treatment. Much of the early work on CTL-019, now renamed tisagenlecleucel, took place in the university's labs and clinics.

By modifying immune cell DNA, this method could, in theory, lead to other cancers - a longtime concern for gene therapy.

The global CAR-T market is estimated to hit $8.5 billion by 2028, according to a report released in February by Coherent Market Insights. Another risk is that there are many other players that are developing treatments in the CAR-T space as well.

Novartis also convinced the advisory committee that its complicated manufacturing process could be fast and consistent.

To use the technique, a separate treatment must be created for each patient - their cells removed at an approved medical center, frozen, shipped to a Novartis plant for thawing and processing, frozen again and shipped back to the treatment center.

Such a complex system for making personalized treatments is likely to drive up their cost, and the next big hurdle (assuming an FDA approval this fall) is to win over insurers. The cells would then be refrozen and sent back to the patient.

The drug uses a new technology known as CAR-T, or chimeric antigen receptor T-cell therapy, which harnesses the body's own immune cells to recognize and attack malignant cells.

  • Sylvester Abbott