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With Eye On FDA, Kite Says CAR-T For Lymphoma Holds Up After 6 Months

Xconomy National — 

Kite Pharma released more data this morning that it hopes will lead this year to the first commercial approval of a cutting-edge cancer treatment known as CAR-T therapy.

The Santa Monica, CA, firm will soon ask the FDA for approval to use its CAR-T therapy, known as axicabtagene ciloleucel, to treat patients with desperate cases of non-Hodgkin lymphoma, or NHL. An FDA decision could come before year’s end. Kite (NASDAQ: KITE) CEO Arie Belldegrun used rather lofty rhetoric to describe the results. “Few have been granted the opportunity to potentially change the course of medical history,” he said on a conference call with analysts Tuesday morning. “We at Kite believe we’ve been provided such an opportunity. Today is a defining moment of CAR-T therapy as we announce exceptional outcomes with just a single infusion.”

In September, Kite reported results from 62 Zuma-1 patients three months after treatment. Today’s results, expanded to 101 patients six months post-treatment, are similar or better in several ways. Patients did not seem to suffer more relapses, and no alarming deaths or major unexpected side effects cropped up, according to the company’s report. Belldegrun called the program “one of the biggest breakthroughs in cancer therapy since the introduction of combination chemotherapy more than 60 years ago.”

If the topline results hold up longer, they could eventually match Belldegrun’s optimism. For now, Kite’s CAR-T therapy has knocked out the cancer in about one-third of the 101 patients in the Zuma-1 trial. It’s important to note that patients on other experimental CAR-T treatments have relapsed after positive early signs. But there are some hints that the outcomes could last beyond the six-month study cutoff that the company described today.

The patients were treated with a single dose of their own T cells and no other follow-up treatments, according to Kite officials. In CAR-T cell therapy, a patients’ T cells are extracted and genetically modified outside the body to become more efficient cancer killers, then infused back into the body. (CAR stands for chimeric antigen receptor, the main genetically modified part of the cell.) No CAR-T has yet come to market, although Novartis (NYSE: NOV) has an experimental program to treat kids with acute lymphoblastic leukemia that could go before the FDA this year. In a different kind of cancer immunotherapy, called checkpoint inhibition, four drugs have been approved to treat certain skin, liver, lung, head-and-neck, and bladder cancers, as well as NHL.

Of the 101 Zuma-1 patients, 41 percent had at least some tumor shrinkage—a partial response to the treatment—after six months. Nearly all those patients (36 of 41) had no sign of disease—a complete remission—after six months.

The study was split into two patient groups with different types of NHL. The largest subgroup, 77 patients with diffuse large B-cell lymphoma, or DLBCL, had slightly lower response rates—36 percent had a partial response, 31 percent had a complete response—than the overall group. Kite said it would ask the FDA to approve axicabtagene ciloleucel for three types of DLBCL and two other types of NHL.

Kite shares were up more than 22 percent to $69.67 in mid-day trading.

Kite officials were optimistic that the number of patients with complete responses could grow in coming months. They were basing their optimism on one patient who converted from a partial response to a complete one nine months after treatment, and four more who have not been in complete remission long enough to make the six-month cutoff. Other long-lasting partial responses have occurred in Zuma-1 and in a previous study at the National Institutes of Health using a previous version of axicabtagene ciloleucel. Kite chief medical officer David Chang characterized these patients, whose cancer was not quite eradicated, as “deep responders” who might convert to a complete response. When asked for more details about potential conversions, Chang declined to share, saying more details would come at a future medical meeting.

How those rates hold up beyond six months is an open question and an important one because of the relapse rate with other experimental CAR-T programs. Kite said the median length of time between treatment and follow-up assessment for Zuma-1 patients was 8.7 months, but it is too early to assess the group’s overall survival rate. That suggests that the overall survival rate will exceed how long these types of NHL patients have historically survived after other treatments, a median of 6.6 months, according to Kite’s own study called SCHOLAR-1.

Safety is a top concern for CAR-T therapy. Juno Therapeutics (NASDAQ: JUNO) of Seattle has had to halt its lead program, treating adults with ALL, after five patients died of cerebral edema, or swelling in the brain. Juno has yet to disclose the results of its inquiry into the deaths or spell out the fate of the stalled program. In January, Juno CEO Hans Bishop said the company had one more experiment to conduct in the inquiry.

Kite officials were quick to note that no Zuma-1 patients experienced cerebral edema. Three patients have died during Zuma-1; two were considered related to their treatment.

At least one analyst saw the Kite results as positive for Juno, whose lead program is now an NHL treatment with Phase 1 results. It could enter a pivotal trial this year. “We think the results are incrementally positive for Juno and the CAR-T category more broadly as some investors have questioned the ability of CAR-T cell therapy to generate durable remissions in lymphoma,” Leerink’s Michael Schmidt wrote in a research note Tuesday.

Kite reported today that serious incidents of the two most common side effects of CAR-T therapy, cytokine release syndrome and neurological abnormalities, occurred in 13 and 28 percent of the patients, respectively. The rates were higher, 18 and 34 percent, in the interim 62-patient report in September.

Image of human lymphoma tumor cells courtesy of the National Cancer Institute.