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.

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.

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.

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.

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.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Tim Mayleben (file photo)

Es­pe­ri­on's goldilocks cho­les­terol fight­er wins FDA ap­proval — will its 'tra­di­tion­al' pric­ing ap­proach spur adop­tion?

It’s more effective than decades-old statins but not as good as the injectable PCSK9 — the goldilocks treatment for cholesterol-lowering, bempedoic acid, has secured FDA approval.

Its maker, Esperion Therapeutics, is betting that their pricing strategy — a planned list price of between $10 to $11 a day — will help it skirt the pushback the PCSK9 cholesterol fighters, Repatha and Praluent, got from payers for their high sticker prices.

The sky-high expectations for the pair of PCSK9 drugs that were first approved in 2015 quickly simmered — and despite a 60% price cut, coupled with data showing the therapies also significantly cut cardiovascular risk, sales have not really perked up.

Esperion is convinced that by virtue of being a cheaper oral therapy, bempedoic acid will hit that sweet spot in terms of adoption.

“We’re kind of like the old comfortable shoe,” Esperion’s chief commercial officer Mark Glickman remarked in an interview with Endpoints News ahead of the decision date. “It’s an oral product, once-daily and nontitratable — these are things that just resonate so true with patients and physicians and I think we’ve kind of forgotten about that.”

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James Collins, Broad Institute via Youtube

UP­DAT­ED: A space odyssey for new an­tibi­otics: MIT's ma­chine learn­ing ap­proach

Drug development is complex, expensive and comes with lousy odds of success — but in most cases, if you make it across the finish line brandishing a product with an edge (and play your cards right) it can be a lucrative endeavor.

As it stands, the antibiotic market is cursed — it harbors the stink of multiple bankruptcies, a dearth of innovation, and is consequently barely whetting the voracious appetites of big pharma or venture capitalists. Enter artificial intelligence — the biopharma industry’s cure-all for the pesky process of making a therapeutic, including data mining, drug discovery, optimal drug delivery, and addressable patient population.

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Gilead los­es two more patent chal­lenges on HIV pill, set­ting up court­room fight in Delaware

Gilead sustained two more losses in their efforts to rid themselves of an activist-backed patent lawsuit from the US government over a best-selling HIV pill.

Urged on by activists seeking to divert a portion of Gilead’s revenue to clinics and prevention programs, the Department of Health and Human Services made a claim to some of the patents for the best-selling HIV prevention drug, Truvada, also known as PrEP. Gilead responded by arguing in court that HHS’s patents were invalid.

Today, the US Patent and Trademark Office ruled that Gilead was likely to lose the last two of those challenges as well. The USPTO ruled against Gilead on the first two patents earlier this month.

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Special report

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Jim Scholefield via PR Newswire

Mer­ck los­es its chief dig­i­tal of­fi­cer, spot­light­ing tal­ent hunt for the hottest ti­tle in Big Phar­ma

Over the last few years we’ve seen the chief digital officer title become one of the hottest commodities in Big Pharma as global organizations hunt the best talent to sharpen the cutting edge of their tech platforms.

But Merck just discovered how hard it may be to keep them focused on pharma.

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Bank­rupt an­tibi­otics mak­er Ar­a­digm turns to old part­ner/in­vestor for fi­nal $3M fire sale

Grifols once paid Aradigm $26 million for a stake in its inhaled antibiotics. But with Aradigm now in bankruptcy, the Spanish drugmaker is dishing out a final $3.2 million to buy it all.

The fire sale — which comes one year after Aradigm filed for Chapter 11 following a regulatory trifecta for disaster — will see Grifols obtain assets and IP to Apulmiq (formerly Pulmaquin and Linhaliq in Europe), Lipoquin and free ciprofloxacin. In addition to waiving its claims in the bankruptcy case, Grifols also agreed to milestone payments up to $3 million more upon any regulatory approvals.