First-Ever CRISPR Trial Points to Looming Problems

First-Ever CRISPR Trials Points To Looming Problems
June 29, 2016
By Karl Thiel for

The first trial of a CRISPR-Cas9 drug in humans may soon begin, and it isn't being sponsored by a pharmaceutical or biotech company. It's happening through the University of Pennsylvania, funded largely by The Parker Institute—the philanthropy recently created by billionaire Sean Parker.

I wrote in April about the role of billionaires in biotech, how they gravitate toward blue-sky longevity programs, and how only they may be willing to undertake the kinds of timelines and financial losses necessary to move certain kinds of research forward. But CRISPR shouldn't fall into that category. Widely regarded as one of the most exciting developments in biology in a decade or more, CRISPR has attracted plenty of venture capital, already launched one "pure play" public company (Editas Medicine) and drawn attention to ongoing programs at others.

Yet for all the vaunted nimbleness of venture-backed startups, it is academia that is moving the ball forward. In a recent interview with Forbes' Matthew Herper, Parker and University of Pennsylvania professor Carl June suggested that this has to do with the bureaucracy and administrative burdens associated with even relatively small companies. That's undoubtedly part of it, but I think there are a few other things going on:

• First, companies may simply be more cautious. CRISPR-based therapeutics are tremendously exciting, but they certainly pose some safety risks. Nobody wants a Bial-type tragedy on their hands, and everyone will certainly work hard to move forward responsibly. But there can be differing interpretations of what that means.

• Second, the billionaire effect probably is at play here. With Parker footing the bill, this debut program has an ambitious goal: They are aiming to make T cells "better than nature made them"—for example, to not respond to a PD-1 switch that might otherwise make them ignore cancer cells as invaders. Editas' first program is going after a rare form of congenital blindness. That means working within a relatively closed system, the eye, with people who are already blind—lowering the stakes of unknown consequences significantly.

• Finally, because it is a University of Pennsylvania program, they have easier access to patients.

It's these latter two points that get at a larger issue facing the biotech industry.

Where Will The Patients Come From?

Right now, we're experiencing an embarrassment of riches when it comes to cancer targets and strategies. Bruce Booth at LifeScienceVC recently referred to the "exploding supernova known as immuno-oncology"—a huge boom in therapies, both commercial and (especially) experimental that, alone and in combination, are improving the survival curve in cancers.

It's great news in the big picture, but it's not entirely clear the industry is optimized to handle it.

Opening up new scientific territory doesn't necessarily send commercial researchers scurrying to the far corners of possibility. Rather, they cluster around certain ideas. You can see the reasoning: A proven therapeutic approach is less risky than something novel, and being second or third to the party doesn't necessarily mean you can't succeed in the market—or even, if you're lucky, come to dominate it. Thus we have a multitude of PD-1 and PD-L1 inhibitors in development—Booth counted 70 disclosed programs in preclinical development or later. Parker's CRISPR program would crowd into this territory, too.

At ASCO Earlier this month, FDA oncology chief Richard Pazdur publicly chided industry for piling into one area so aggressively, asking companies: "Would we be better off spending those resources into looking at more novel drugs?" History shows that until we start seeing proof that newcomers are commercial flops, industry's answer will be 'no.'

But there's a bigger problem here. There are a simply enormous number of clinical trials ongoing right now. Booth counted up nearly 1,000 trials just involving the four improved immuno-oncology drugs, which doesn't count further investigator-initiated trials not yet disclosed.

Here's another statistic, this presented by the National Cancer Institute and in 2010: Only 3% of adults with cancer participate in clinical trials. The American Cancer Society currently counts about 5.2 million people in the U.S. who are at zero to five years from a cancer diagnosis. If just 3% of those folks will participate in clinical trials, that suggests 156,000 participants. So even if participation rates have increased since those NCI figures came out, you can see where the trouble starts.

According to another NCI analysis of 500 trials, a full 40% of cancer studies failed to reach full enrollment. The University of Pennsylvania's June report suggested that researchers will increasingly look outside the U.S. for patients, but it's not clear how much that will help—according to one study (admittedly dating back to 2005, so perhaps things have changed), trial participation rates are even lower in India and Europe.

Companies are well aware of the challenges and are jockeying for position. This month, Celgene announced a new partnership with four academic institutions—The University of Pennsylvania, Johns Hopkins, Columbia University and Mt. Sinai. Its $50 million investment gets it an option to develop cancer research coming from the consortium over the next 10 years. But it also gets its access to patients and trial support. As the company noted in its release, "The four institutions collectively care for more than 30,000 new cancer patients each year, and have nearly 800 faculty members who are active in basic and clinical research, and clinical care."

Celgene is hardly the first company to forge tight academic partnerships. They've always played a role in industry but became increasingly popular following two trends that have marked the past decade: Sharp cutbacks in R&D on the industry side, and declines in NIH finding on the university side. Deals have traditionally been narrowly focused on specific technologies. Access to patients is often the unspoken part of broader collaborations, but it's coming into sharp focus. The next big winners in cancer may be defined by who has access to patients more than anything else.

-Karl Thiel

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