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.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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In­vestors give ail­ing Unum a lease on life and a whole new suite of ex­per­i­men­tal can­cer drugs

Investors, it seems, are willing to give Unum Therapeutics one last shot — or at least one last shot to a company of that name.

The ailing cancer biotech, beset by a series of clinical holds and multiple failed lead programs, announced today that they’ve acquired Kiq LLC and that investors are putting in $104 million to advance Kiq’s pipeline of kinase inhibitors. Unum shareholders will now own only 16.2% of the company and CEO Chuck Wilson indicated that the cell therapies the biotech has worked on since its founding may be on their way out, saying Unum will “explore strategic options” for those products.

RA Cap­i­tal dou­bles down on Sid­dhartha Mukher­jee's vi­sion for a new cell en­gi­neer­ing ap­proach, lead­ing Vor's $110M Se­ries B

Vor Biopharma is muscling up.

CEO Robert Ang, who was reluctant to divulge the headcount when discussing his move from Neon Therapeutics to Vor last August, readily offered that the team has grown from 6 to 50 in less than a year. The biotech is moving to a larger office on Cambridge Parkway Drive in weeks, giving it more space to complete the IND-enabling work and manufacturing scale-up — conducted by a CDMO partner — in preparation for clinical trials planned for the first half of 2021.

Covid-19 roundup: Left out no longer, No­vavax se­cures largest Warp Speed deal yet: $1.6B

It looks like Novavax won’t be left out of Operation Warp Speed after all.

A month after the Gaithersburg, MD biotech saw its shares tumble when it was left off the first reported list of finalists for the White House’s Covid-19 vaccine accelerator, HHS and the Department of Defense have announced a $1.6 billion deal to scale up their Covid-19 candidate. It is the largest deal HHS has announced yet, eclipsing the $1.2 billion deal the administration reached with AstraZeneca in May.

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Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

A lit­tle biotech slaps back at a 'crim­i­nal' short at­tack, vow­ing to pur­sue a pros­e­cu­tion of their case

As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

A boom­ing Drag­on­fly is tak­ing its TriN­KETs to Copen­hagen as the lat­est Bris­tol My­ers pact spurs ex­pan­sion plans — out­side the US

Bristol Myers Squibb is making a habit out of collaborating with the crew at Dragonfly, adding their 3rd deal in a series that now will take them into newly charted R&D territory. And the fast-growing team at the Cambridge-based biotech is adding a facility in Copenhagen for its next growth spurt, where the government is making it easy to recruit scientists internationally as the U.S. throttles back.

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Covid-19 roundup: Teamed up with NIH, Re­gen­eron launch­es PhI­II pre­ven­tion tri­al for an­ti­body cock­tail

As Regeneron moves its antibody cocktail into Phase II/III trials testing REGN-COV2 as a treatment for both hospitalized and non-hospitalized patients with Covid-19, the biotech is also starting a Phase III in the prevention setting.

The National Institute of Allergy and Infectious Diseases — which orchestrated the large, randomized study for remdesivir that produced positive results — will jointly run the study.

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