There has to be a better way to handle Duchenne drugs; Let’s get to the bottom of the Juno debacle

Endpoints assesses the big biopharma R&D stories of the week, with a little added commentary on what they mean for the industry.

thumb down Long after it became apparent that PTC’s Duchenne drug doesn’t work, the EMA’s green light is intact

I never understood why the EMA would suddenly reverse itself in 2014 and allow PTC to sell ataluren as its only approved therapy on the continent for Duchenne muscular dystrophy. And it was even more perplexing to see the European regulator come back last year and decide to allow the drug to remain on the market as PTC lined up a new late-stage study over an expansive 5-year grace period.

At that point, not only did the EMA know full well that the drug had simply failed a Phase III trial for Duchenne, supposedly designed so that it would overcome the flaws in its failed Phase IIb trial, but the FDA had locked the door to PTC’s executive crew, unwilling to spend any time reviewing a drug that was woefully unacceptable for marketing.

This week, PTC put what should have been the last nail in ataluren’s coffin with fresh evidence that this drug is a dud. It failed the Phase III for cystic fibrosis. Case closed.

Except that it’s not and won’t be. This drug will continue to be sold despite the fact that it has repeatedly and decisively failed to clear late-stage trial hurdles. Even NICE was willing to endorse it for the UK after working out a price with PTC. PTC expects to earn more than $100 million this year from sales. And it has the backing of patient advocates — Duchenne families — who swear by it.

As we found out from Sarepta’s Exondys 51, though, regulators can be persuaded to overlook gaping holes in a Duchenne drug’s development program to make way for an approval.

There has to be a better way. If the FDA and EMA want to handle new drugs for Duchenne MD according to a different standard, then they should set up special groups inside the agencies that can help biotechs direct small but better designed studies that can offer real-world evidence of efficacy and safety. The path we’re on now is a disaster for patients, families and the societies forced to pay for these wildly expensive, unproven drugs.

thumb down This is no time to let Juno off the hook for JCAR015 fatalities

Juno this week said that it decided to do something that everyone in biotech knew was inevitable 10 minutes after the last two patients were killed by JCAR015. It killed the program.

The CAR-T company, once a leader in the field and now a worrisome follower, felt that it could explain everything. But that would take a Phase I trial and who has time to go back to the drawing board? Especially when you have another candidate ready to take the lead.

But let’s all take a moment to reflect. Juno was subjected to one of the shortest clinical holds the FDA ever imposed on a biotech company. It is engaged in a cutting-edge field with new technology. And its lead drug killed at least five people that we know of, with the full tally coming after the drug was allowed back into the clinic. Two other cerebral edema deaths occurred in other studies.

What was the FDA’s role in all of this? Why did it accept a lame, and lethally incorrect, explanation from Juno that taking fludarabine out of the preconditioning regimen would make JCAR015 safe again? What will it do differently next time?

And why not require a well-financed biotech like Juno to go ahead and do that Phase I to see what went wrong?

Juno, like every other company in its shoes, will likely never want to speak of JCAR015 again. The derailment has slammed its stock price and put it well behind Kite and Novartis. It’s up to Juno and the FDA, though, to provide some explanation here of what went wrong and how to make sure it never happens again.

The FDA can’t afford to let Juno off the hook again. Regulators shouldn’t let themselves off the hook either.

thumb down Trump says the FDA is slow and burdensome. We don’t think so.

Once Donald Trump has sunk his teeth into a perceived grievance, he can’t let go. And right now he’s mightily aggrieved at the FDA, which this week once again earned a few kicks from the president in his address to Congress.

The drug approval process, he says, is slow and burdensome, and he plans to make some big changes. If you deregulate drug development, he has said before, drugs can speed through the FDA faster and the price will drop.

That, of course, is simply ridiculous. We’ve seen quite a few drugs speed through the review process in the last few years, and the price was in no way discounted as a result.

When Biogen, which has its own efficiency issues to address, got an approval for Spinraza last December just three months after it was filed, do you think the big biotech offered a discount as a result?

Not a chance. It priced the rare disease drug at $750,000. With its Tecfidera franchise on the wane, Biogen needs new revenue to satisfy investors. And how is that in any way unusual?

Gilead was a model of efficiency and expertise when it whipped through a development program for new hep C drugs. Sovaldi was the third drug approved under the FDA’s breakthrough drug designation, designed to help speed development timelines. It originally cost a small fortune. Cancer drug development has been revolutionized by the BTD program over the past few years. Have prices come down?

There are things that the FDA can do better that will lower some drug costs. But unless the president plans to simply gut development rules — a real possibility — don’t look for a faster FDA to bring down drug prices. Lower costs on drug programs do not lower prices.

thumb The biotech startups keep coming

Near the beginning of this week I had the pleasure to talk to some of the people behind two biotech startups that are truly looking to break new ground in drug R&D. Michael Gilman is back with his third upstart, Arrakis, looking to drug some previously undruggable targets with small molecules that can go after RNA. Just think about RNA drugs that can get easily into the brain. And that’s just one feature of what is going on here. The possibilities are considerable. Then I spoke with Eric Olson at UT Southwestern, who’s spinning out his CRISPR/Cas9 work on Duchenne muscular dystrophy. Like Arrakis, Exonics is still in the preclinical stage. But its potential is still easy to see. Here at the start of 2017 we’re seeing a whole range of interesting new biotech startups come our way. This all speaks well to the potential that biotech has to do truly pioneering drug development work. The money that has been flowing into the field for the past few years is being put to good use.

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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