This is a recurring column on clinical research in the early stages of development, which is referred to as phase 1. These are treatments being used for the first time in a small number of human patients to determine safety, dosing and general pharmacological activity.
In the world of cell therapy, Legend Biotech Corp. and big pharmaceutical partner Johnson & Johnson showed that their CAR-T therapy called cilta-cel could make a big difference in the blood cancer multiple myeloma in early-stage trials.
The companies presented data from a combination phase 1 and phase 2 trial at the 2020 annual meeting of the American Society of Hematology, showing continued safety with 97% of patients in the study responding to the treatment.
Legend Biotech CEO Ying Huang told S&P Global Market Intelligence that, even more importantly, 67% of patients receiving cilta-cel achieved what is called a "stringent complete response," or an absence of detectable cancerous cells in the bone marrow.
"This is a very important therapy for these patients with multiple myeloma who really have exhausted all the treatments that are on the market today," Huang said.
This will lead to the companies discovering the long-term durability of cilta-cel in multiple myeloma patients as the study, called CARTITUDE-1, continues, Huang said.
Cilta-cel is a specialized cell therapy that targets the B cell maturation antigen, or BCMA, which is a protein that is highly expressed on myeloma cells. During CAR-T, or chimeric antigen receptor T cell, therapy, a patient's immune cells are removed and modified with the ability to resist cancer cells. When the cells are returned, the patient's immune system can better fight the cancer.
The ultimate approval for cilta-cel in the U.S. will depend on completion of that long-term data, which will require further follow-up in the phase 2 part of the study.
Legend Biotech CEO Ying Huang
"The first two CAR-T therapies were only approved back in 2017, so we've only got three years of commercial experience in the field — there's a lot of room to grow in the future," Huang said.
The only two cell therapies approved in the U.S. are Kymriah from Novartis AG for acute lymphoblastic lymphoma and Yescarta from Gilead Sciences Inc. for large B-cell lymphoma, and only in patients who have not responded to other therapies.
No CAR-T therapy has been approved yet for multiple myeloma, which remains largely incurable, according to a September article published in the journal Nature Reviews Clinical Oncology.
CAR-T therapies have limitations, such as difficult manufacturing and a high price point for reimbursement, Huang said. A cell therapy from Bristol-Myers Squibb Co. called liso-cel has had regulatory delays due to manufacturing plant inspections that were put off during the COVID-19 pandemic.
But Huang said the CAR-T therapy field is becoming more accessible, and with J&J, Legend is ensuring delays will be minimal down the road, even at this early stage of the process. The hope is that the companies can submit an application to the U.S. Food and Drug Administration for approval in 2021.
"I do believe we are at the beginning of a long-term growth curve for CAR-T as a field," Huang said. "We're working really hard to be sure that we have a robust manufacturing process, and that should be ready for FDA inspection and commercial launch."
Legend is also looking to a mid-stage clinical trial for cilta-cel to demonstrate the therapy's effectiveness as an earlier treatment for multiple myeloma patients and then a larger 400-patient phase 3 trial as they approach registration with regulatory bodies, Huang said.