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.

UP­DAT­ED: Roche bags 'break­through' an­ti-fi­bro­sis drug in $1.4B biotech buy­out deal

Roche is snapping up a “breakthrough” anti-fibrotic drug in a $1.4 billion buyout.

The pharma giant announced Friday that it is acquiring Promedior, primarily to get its hands on PRM-151, a recombinant form of human pentraxin-2 (PTX-2) protein that has nailed down mid-stage clinical data on idiopathic pulmonary fibrosis and demonstrating its potential for a range of fibrotic conditions.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

(Image: Associated Press)

Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

Federal Trade Commission commissioner Rohit Chopra testifies on Capitol Hill (AP Photo/Susan Walsh)

FTC clears Bris­tol-My­ers’ $74B deal to buy Cel­gene — but Dems sig­nal a po­ten­tial hard shift against Big Phar­ma M&A

Bristol-Myers Squibb’s record $74 billion takeover of Celgene is a done deal. And it will all be over — except for the lingering complaints from die-hard Celgene investors — on Wednesday.

Like much else that’s going on in Washington these days, the vote among the 5 FTC commissioners split along party lines, with the 3 Republicans voting to clear the way and the 2 Democrats steamed over what they see as a major M&A move that will lessen competition and innovation. And that split has big implications for the M&A side of the business if the Dems take the White House in 2020.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis spin­out’s first an­ti-ag­ing PhI­II is a flop, so now they’ll turn to Parkin­son’s chal­lenge as shares wilt

Novartis spinout resTORbio is grappling with the collapse of its lead clinical program this morning — an anti-aging R&D failure that will badly damage their rep in the field.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: In a first, FDA green-lights use of a Chi­nese built can­cer ther­a­py — and more are com­ing

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

BeiGene’s drug, branded as Brukinsa, has secured accelerated approval for adult patients with mantle cell lymphoma (MCL) — a typically aggressive, rare, form of blood cancer — who have received at least one prior therapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

What does $62B buy you these days? A lot, says Take­da ex­ecs as the phar­ma play­er promis­es a block­buster R&D fu­ture

First comes the $62 billion buyout. Then comes the asset auction and reorganization to pay down debt. Now comes the detailed pledge of a bigger, brighter future in drug development.

That’s where Takeda finds itself on R&D day today, about 11 months after closing on their Shire acquisition. R&D chief Andy Plump is joining CEO Christophe Weber and other top members of the team to outline a new set of priorities in the greatly expanded pipeline at Takeda, which has jumped into the top ranks of the world’s pharma giants in the wake of the Shire deal.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.

Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

(Image: Associated Press)

No­var­tis scores its lat­est FDA OK — this time for a new sick­le cell dis­ease drug picked up in a $665M deal

Novartis’ decision to buy Oklahoma-based biotech Selexys 3 years ago for up to $665 million has paid off with an FDA approval today.

Blessed with the FDA’s breakthrough drug designation for a speedy review, the pharma giant has pinned down an approval for crizanlizumab, a new therapy designed to reduce the frequency of painful incidents of vaso-occlusive crises among sickle cell disease patients 16 or older.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.