Monday, October 24, 2016

The Readout by Damian Garde & Meghana Keshavan

Welcome to The Readout, where we bring you the latest in biotech. Follow us on Twitter: @damiangarde@megkesh, and @statnews

CRISPR: Pandora's box in a bottle?

could we really use mosquitoes to fight mosquito-borne diseases? many biologists are itching to try. (Molly Ferguson/STAT)

Could gene editing help eradicate diseases like dengue, Zika, and malaria? And should we mess with evolution to try it?

STAT contributors Luke Timmerman and Meg Tirrell take on those questions in their newest Signal podcast.

India’s top philanthropist already knows his answer: He's all in.

The Tata Trusts of Mumbai, led by chairman Ratan Tata, yesterday announced a $70 million gift to UC San Diego to advance researcher into fighting insect-borne diseases with gene editing.

As Tata noted, UCSD biologist Ethan Bier has been a pioneer in gene drive, which essentially hijacks evolution to push an engineered gene through an entire population of organisms. It could be used, for instance, to create a population of mosquitoes that can't smell humans and thus are unlikely to bite us — or give us diseases.

Or it could be used to create new bioweapons. Pandora's box, indeed.

The sobering truth about new cancer drugs

Most new cancer drugs — despite the sky-high price tags — extend patients' lives by only a few months.

How do they get approved?

Turns out, many cancer trials are designed to show some statistical benefit rather than measure true clinical effectiveness in terms of patient survival, according to a pair of recent analyses. Meaning: They look good on paper, but less so in person.

“What’s sobering: Many of these cancer drugs don’t measure up, clinically,” said Dr. Vinay Prasad, an oncologist at Oregon Health & Science University.

The first analysis, published in JAMA Oncology in September, found that just one in five therapies in recent cancer trials met US standards for delivering meaningful outcomes for extending life. (Those standards vary depending on the type of cancer and other factors.) But about half the trials met the standards for "progression-free survival" — basically, the amount of time a drug is able to keep tumor growth in check.

An analysis this month in the Annals of Oncology, meanwhile, found that fewer than a third of recent randomized controlled trials met the European thresholds for meaningful clinical benefit. 

“These papers are showing that many trials are so big, and so powerful, that they can find benefits, sure,” Prasad said. “But [those benefits] are actually so trivial that we wonder if they ought to have been pursued all along.”

In other words, for all the excitement about new approaches such as immunotherapies, we have a long way to go. “What bothers me in the public narrative is that these drugs will bend cancer mortality on a national level,” Prasad said. “I think we already know that they won’t.”

PhRMA's hunt for allies on the Hill continues

The drug industry was quite the political punching bag this summer, but that didn't slow its efforts to find friends on the Hill. New lobbying disclosure forms show that PhRMA spent $4.1 million in the third quarter. BIO spent $2.3 million.

Among its many targets: PhRMA lobbied against legislation co-sponsored by Senator John McCain that would require drug makers to justify price hikes over 10 percent. The group previously told STAT the bill "will not benefit patients."

Using cell therapy, gene therapy and a medical device to treat ALS

It was a crushing blow for the ALS community when a Biogen drug failed in late stage trials in 2013. Since then, there hasn’t been a ton of promise for treating Lou Gehrig’s disease.

Researchers in Los Angeles hope to change that. We chatted with Clive Svendsen, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, about his experimental approach — which got FDA approval this past week to begin human trials. 

What is it you’re working on? 

We have a combined stem cell and gene therapy approach to treat ALS. We take neural stem cells and engineer them to release a protein, GDNF, that protects neurons. We then inject these stem cells directly into the spinal cord of the patient.

Once you put them in, the stem cells are like tadpoles — they’ll swim to areas of damage, migrating to where neurons are dying in ALS.

They don’t replace the motor neurons, which get the most damaged in ALS — but we’ve found that the astrocytes that support the motor neurons are also sick. So we’re basically rejuvenating the spinal cord area by putting new astrocytes in, making the motor neurons live longer — and they’re releasing a powerful drug, GDNF.

What do you hope to see in patients?

Well, in this safety trial, we’re going to inject the cells in one half of a patient’s lumbar spine, so that they’ll only impact the neurons in one patient’s leg. So we’ll track, over time, whether the paralysis progresses on one side faster than the other.

This isn't a cure, just a safety trial. We're trying to do a good, clean trial and do it correctly. But as a treatment itself, chances are, this won’t work, because ALS is a tough disease. But we’re ready for the next steps. 

What was the regulatory process like for this? 

I have to tell you: It was intense. The document we submitted to the FDA was 4,700 pages. We had to go to the Recombinant DNA Advisory Committee, then to CBER [the FDA's Center for Biologics Evaluation and Research], and then if that wasn’t enough, we had to develop a whole new delivery device for this to inject stem cells into the spinal cord — so we had to go through the Centers for Devices and Radiological Health as well. 

Could this approach to cell therapy be used in other diseases?

Now that we have FDA approval for ALS, we’ll look at testing these cells in other diseases. We’re applying for funding soon to do similar work in Parkinson’s, and have another trial for retinitis pigmentosa. 

Echoes of bubbles past

A string of scientific breakthroughs has stoked investor optimism, lined the pockets of venture capitalists and given rise to a generation of highly valued biotech startups.

But don't get too comfy: “The billions in investment have created an industry choked with copycat, capital-hungry companies lacking the critical mass of technology to survive,” according to a Businessweek cover story. “Biotech faces a reckoning — and it’s going to be ugly.”

Who’s to blame? For one, big pharmaceutical companies, which boost profits “mainly by churning out ‘me-too’ drugs and raising prices” and which have been paying huge sums for biotech companies. Then there are the investment bankers, who earn fat fees and so have “little incentive to keep long-shot companies from going public.”

Sound familiar? Here’s the punchline: That story ran on Sept. 26, 1994.

More reads

  • The average annual retail cost of a specialty drug has outstripped the nation's median household income. (Washington Post)
  • Juno Therapeutics is spending big money on a bet that CAR-T can become a major treatment option for cancer, staking its future on a risky proposal. (Economist)
  • Merck won FDA approval for an antibody that treats Clostridium difficile infection. (Press release)

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Thanks for reading! Until tomorrow,

Damian & Meghana

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