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Talking Cure? For Cancer Immunotherapy, Still Many Rivers to Cross

Xconomy National — 

Cancer is a humbling thing: Our own cells gone bad, killing us from the inside, and so often able to rebound from attack or avoid it entirely. There has been progress fighting some types of cancers, but in no way equal to the resources (or rhetoric) the human race has aimed at the problem.

On stage at Xconomy’s annual Seattle biotech forum last week, I asked veteran cancer researcher D. Gary Gilliland, the new president and director of Seattle’s Fred Hutchinson Cancer Research Center—which brandishes the tag line “Cures Start Here”—if now, more than a decade into the genomic era, we’re justified to talk about cures. “There’s a certain amount of hubris in that tag line, but the point is we can finally see this coming against the backdrop of decades of work,” Gilliland said.

What Gilliland sees coming is cancer immunotherapy, a specialty at Fred Hutch, as the famous research center is known. The red-hot buzzphrase refers to different kinds of treatments, but all have in common the goal of stimulating a cancer patient’s immune system to attack the disease from within.

Gilliland: Decades of work.

Gilliland: Decades of work.

He is no impartial observer. Gilliland has played a role in those “decades of work,” first more than 20 years at Harvard University that included running the leukemia program at the Dana-Farber Cancer Center. More recently, he spent four years as head of oncology R&D at Merck, where he oversaw part of the development of pembrolizumab (Keytruda), one of only a few cancer immunotherapies to win approval.

Gilliland sees “a tidal wave of immunotherapeutic approaches” on the horizon, but to be clear, the wave has not arrived yet.

Cancer immunotherapy has helped drive the biotech financial boom the past couple years, with the biotech indices hitting all-time highs in March. A bit of froth has come off the top of the markets in the past month, so perhaps it’s a good time for a pause, a breather, a reality check. What needs to happen for that wave to reach patients? (Let’s pretend for a moment that tidal waves bring lots of wonderful health benefits, not death and destruction.)

We’ll start with the kind of cancer immunotherapy that Gilliland oversaw at Merck. Pembrolizumab (approved in the U.S. last September) is a monoclonal antibody, a kind of drug the industry has been developing and manufacturing for two decades. Four for cancer immunotherapy have been approved; three are “checkpoint inhibitors,” which disrupt a protein that cancer cells use to put a brake on the immune system.

The only checkpoint inhibitor with more than a few months on the market is ipilumumab (Yervoy), approved in 2011 for the skin cancer melanoma that has spread to other parts of the body or can’t be removed by surgery. It’s an important medicine, but it can sometimes be too toxic for patients.

Ipilumumab causes skin problems in up to 25 percent of patients, according to Jennifer Nam Choi, director of the Yale School of Medicine’s oncodermatology clinic. There are other immune-related side effects, too, serious enough to merit a “black box” warning from the FDA. Choi and other doctors have told me the potentially deadly side effects deter some physicians, who don’t have access to the latest research and resources, away from the drug.

“The rash”—which sounds tame but can be quite severe—“does not discourage us from using the drug since we know how to deal with it,” Choi told me. “But I can see how in smaller clinics and practices, it could be a reason.” (Choi noted that the two other approved checkpoint inhibitors, nivolumab (Opdivo) and pembrolizumab, so far seem to provoke milder side effects.)

The risks are worth taking when patients are otherwise facing near-certain death, as with the melanoma ipilumumab treats. The 5-year survival rate is 15 percent with a median survival between 8 and 9 months, according to a coverage report from insurance giant Aetna.

But to apply to a broader cancer population, checkpoint inhibitors need to get better. Keith Flaherty, who runs the Termeer Targeted Cancer Center at Massachusetts General Hospital in Boston, calls them “a phenomenal discovery” but to date “no panacea.”

That’s why every pharma company in the space is scrambling to try combinations. That’s the next hurdle for cancer immunotherapy: finding the right combinations out of dozens of possibilities. Even with some of the richest companies on Earth in the drug business, the costs could become prohibitive. When I asked Gilliland about the problem, he said “thoughtful and clever trial designs” would be needed—a topic he has written about in the past.

Better diagnostics are necessary, too. Adaptive Biotechnologies of Seattle has reeled in nearly $400 million in private funding since the start of 2014, including $195 million last week, because its backers believe … Next Page »

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  • Dieter Hovekamp

    Your article leaves out another type of T-Cell therapies that have been pioneered by the mTCR spin-outs from German Medigene AG and are silently in the focus of all big Pharma now: TCR based therapies.

    Beside Medigene and its UK pioneers Adaptimmune and Immunocore – Eli Lilly and Juno recently bought into other German companies BioNTech and Stage Cell. Kite and Bellicum try to catch up in TCRs as well with new collaborations this spring – also these are all often wrongly assigned as CAR-T play.

    The reason for this stealth can best be seen in this picture from the Immunocore Website (see http://www.immunocore.com/technology/targets ) – its all about new targets!