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In Year of CAR-T Trouble, Can Bluebird, Penn Make Headway in Myeloma?

Xconomy Boston — 

Several drugs have been approved to treat multiple myeloma, a cancer of the bone marrow, in recent years. But it remains a nasty, persistent disease. Most everyone relapses.

Two rival groups, Bluebird Bio and researchers at the University of Pennsylvania, are presenting data in coming days to make a case that a cutting-edge therapy known as “CAR-T” treatment can become relapsed patients’ last line of defense—and perhaps more.

Both groups are reporting very early data, from Phase 1 trials, in a handful of patients. The peek Cambridge, MA-based Bluebird (NASDAQ: BLUE) is providing today seems to be superior to the early results from Penn, but there are strong caveats, too: Both groups are just beginning a long road of testing in patients, and CAR-T therapies for other blood-borne cancers have shown promising early results only to see their effects fade.

“My experience is that CAR-T therapies may last for several weeks, maybe even a month or six weeks before they slowly die down,” says Maung Myo Htut, a hematologist at City of Hope National Medical Center in Duarte, CA, who isn’t involved with Bluebird or Penn. “If we can prolong disease control by [at least] six months, I’d be very happy to use it.”

In multiple myeloma, the bone marrow’s plasma cells—a type of immune cell that normally churns out infection-fighting antibodies—grow rapidly and abnormally and crowd out healthy red and white blood cells. According to the American Cancer Society, about 30,000 people in the U.S. will be diagnosed with multiple myeloma this year. It’s the third most common blood cancer in the country after lymphoma and leukemia.

Most forms of CAR-T treatments use genetic engineering to turn a patient’s own immune cells into better cancer killers. Even if they can be tuned to wipe out multiple myeloma for several months for patients who have tried and failed several prior treatments, they must prove that the benefits last and are not outweighed by significant side effects. The CAR-T field is on edge after a major developer, Juno Therapeutics (NASDAQ: JUNO), reported last week more patient deaths in a high-profile trial of its most advanced therapy.

So what are the early returns for multiple myeloma? First up is Bluebird, which will present data tomorrow on its treatment, bb2121, at a conference in Germany. Bluebird reports that 11 patients have been treated, nine of them long enough as of Nov. 18 to measure the treatment’s efficacy. Seven of those nine have responded in varying degrees. Two patients have had a “stringent” complete response, which means no detectable plasma cells—the immune cells that turn cancerous in multiple myeloma—in the bone marrow four and six months after treatment, respectively. A third patient had a “very good partial response,” meaning more than a 90 percent drop in levels of a protein made by myeloma cells. The other four had “partial responses,” more than a 50 percent drop in the levels of that protein.

Bluebird chief medical officer David Davidson says the most significant side effects so far were “mild and well tolerated” cases of cytokine release syndrome, an immune reaction that can be life threatening. More specifics will emerge at tomorrow’s meeting. “It’s still early and we have to watch it play out,” says CEO Nick Leschly, “[but] we’re seeing quite a bit of efficacy without all the toxicity. And that’s the big win we were looking for.”

Side effects are a real concern. The patients who died in Juno’s trial succumbed to severe brain swelling. Other experimental CAR-T therapies have triggered severe, sometimes fatal cytokine release syndrome. But without significant safety problems so far, Bluebird officials say they can continue testing higher doses of bb2121, which so far have performed better (six out of six patients responded) than low doses (one out of three patients responded).

It took two and four months post-treatment, respectively, to get the two best responses, Davidson says. Will Bluebird see better, longer-lasting results as its doses climb? Or will higher doses over longer periods of time prove too dangerous?

“You have to wait it out, especially with this kind of trial, but [bb2121] looks very promising,” says Htut of City of Hope.

The Penn group, meanwhile, will report interim Phase 1 data from its treatment, CART-BCMA, next week at the American Society of Hematology’s yearly meeting in San Diego. The group published a preview in November that detailed six patients. One patient who had failed 11 prior therapies has an ongoing stringent complete response lasting more than seven months. A second patient had a very good partial response that held up for five months before the disease progressed. The other four have had little or no response.

What differentiates Bluebird’s treatment from Penn’s, at least at this early stage, are the side effects. In the Penn study, one patient suffered seizures and vision loss serious enough to prevent testing a higher dose. Penn also reported … Next Page »

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