June 5, 2017
By Mark Terry, BioSpace.com Breaking News Staff
It’s not exactly news that there’s an ongoing horse race to see who can dominate the CAR-T market. What came as a surprise was a presentation by China’s Nanjing Legend Biotech at the ASCO meeting held in Chicago that showed phenomenal results in early multiple myeloma (MM) with its CAR-T product.
It was just a week ago that Switzerland-based Novartis announced dazzling findings from a pilot study of its CAR-T therapy, CTL119, in nine patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had been on Imbruvica (ibrutinib) for at least six months, but were not in complete remission. In three months, eight of the nine patients showed no signs of CLL in their bone marrow. One patient had a partial response. One patient did not produce evaluable data.
Chimeric antigen receptors (CAR) are engineered to target any cancer antigen desired. The engineered T-cells are then reintroduced into the patient programmed to attack specific cancer cells. In trials, it has been enormously successful, although a common serious side effect is cytokine release syndrome (CRS), which at its most severe is life-threatening.
Nanjing Legend Biotech’s data was in 35 relapsed, drug-resistant patients with MM. Thirty-three, or 94 percent, showed clinical remission that ranged from complete to partial response. According to the presentation, there was a 100 percent objective response rate.
John Carroll, writing for Endpoints News, says, “Of the first 19 patients to reach the four-month mark specified in the trial, a remarkable 14 achieved a ‘stringent’ complete response (SCR), which is associated with longer survival times. And five patients who hit the one-year mark were still in the sCR stage.”
Other leaders in the field besides Novartis are Kite Pharma and its CTE-C19, with, like Novartis’s product targets CD19, and Bluebird Bio ’s bb2121. Bluebird’s product targets the same BCMA, the same antigen as Nanjing Legend Biotech’s LCAR-B38M. Juno Therapeutics is also in the race, although the company had a major setback when it abandoned its JCAR015 to refocus on JCAR017 because of patients deaths from cerebral edemas.
Angus Liu, writing for FierceBiotech, says, “Currently leading the pack are Novartis’ CTL019 and Kite’s KTE-C19, both targeting CD19, both with FDA priority review in hand, with Novartis slightly ahead by about two months in terms of FDA’s scheduled decision date. Although they’re pursuing different initial indications—Novartis for acute lymphoblastic leukemia and Kite for non-Hodgkin lymphoma—the similarity in their approaches could invite direct competitions in the future.”
That’s not the case with Bluebird and Legend, which are both targeting BCMA and evaluating the same indication. Frank Fan, Legend Biotech’s chief scientific officer and interim chief executive officer, told FierceBiotech, that their compound “is a single CAR with antigen binding domain of a non-scFv structure. Our binding domain composed of two different heavy-chain variable domains (single-domain antibodies or VHH) and both VHH domains target the same antigen BCMA but target different epitope.”
Legend Biotech’s study also had problems with cytokine release syndrome, with 85 percent of patients experiencing it, including two with a grade 3 case that required Roche ’s Actemra to control the inflammatory reaction. All patients recovered.
“While it’s still early, these data are a strong sign that CAR T-cell therapy can send multiple myeloma into remission,” Michael Sabel, the William W. Coon Collegiate Professor of Surgical Oncology, Chief, division of Surgical Oncology at the University of Michigan Health Systems, said in a statement. “It’s rare to see such high response rates, especially for a hard-to-treat cancer. This serves as proof that immunotherapy and precision medicine research pays off. We hope that future research builds on this success in multiple myeloma and other cancer.”
