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.

Brent Saunders [Getty Photos]

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan — spelling out $1B in R&D cuts

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

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Af­ter rais­ing $158M, this up­start's founders have star back­ers and plans to break new ground in gene ther­a­py

Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

Today, fully 5 years later, she and Ramamoorthi are taking the wraps off of a $104 million mega-round designed to take the cumulative work of their preclinical formative stage for Encoded Therapeutics into human studies. They’ve now raised $158 million since starting out in Illumina’s incubator in the Bay Area, and they believe they are firmly on track to do something unique in gene therapy.

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Sanofi/Re­gen­eron mus­cle ahead of a ri­val No­var­tis/Roche team, win first ap­proval in key rhi­nos­i­nusi­tis field

Re­gen­eron and their part­ners at Sanofi have beat the No­var­tis/Roche team to the punch on an­oth­er key in­di­ca­tion for their block­buster an­ti-in­flam­ma­to­ry drug Dupix­ent. The drug team scored an ac­cel­er­at­ed FDA ap­proval for chron­ic rhi­nos­i­nusi­tis with nasal polyps, mak­ing this the first such NDA for the field.

An­a­lysts have been watch­ing this race for awhile now, as Sanofi/Re­gen­eron won a snap pri­or­i­ty re­view for what is now their third dis­ease in­di­ca­tion for this treat­ment. And they’re not near­ly done, build­ing up hopes for a ma­jor fran­chise.

Two biotech uni­corns swell pro­posed IPOs, eye­ing a $600M-plus wind­fall

We’ve been wait­ing for the ar­rival of Bridge­Bio’s IPO to top off the wave of new biotech of­fer­ings sweep­ing through Nas­daq at the end of H1. And now we learn that it’s been sub­stan­tial­ly up­sized.

Ini­tial­ly pen­ciled in at a uni­corn-sized $225 mil­lion, the KKR-backed biotech has spiked that to the neigh­bor­hood of $300 mil­lion, look­ing to sell 20 mil­lion shares at $14 to $16 each. That’s an added 5 mil­lion shares, re­ports Re­nais­sance Cap­i­tal, which fig­ures the pro­posed mar­ket val­u­a­tion for Neil Ku­mar’s com­pa­ny at $1.8 bil­lion.

No­var­tis holds back the copy­cat brigade's at­tack on its top drug fran­chise — for now

A fed­er­al judge has put a gener­ic chal­lenge to No­var­tis’ block­buster mul­ti­ple scle­ro­sis drug Gilenya on hold while a patent fight plays out in court.

Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Richard Gonzalez testifying in front of Senate Finance Committee, February 2019 [AP Images]

Ab­b­Vie's $63B buy­out spot­lights the re­turn of ma­jor M&A deals — de­spite the back­lash

Big time M&A is back. But for how long?

Over the past 18 months we’ve now seen three major buyouts announced: Takeda/Shire; Bristol-Myers/Celgene and now AbbVie/Allergan. And with this latest deal it’s increasingly clear that the sharp fall from grace suffered by high-profile players which have seen their share prices blasted has created an opening for the growth players in big pharma to up their game — in sharp contrast to the popular bolt-on deals that have been driving the growth strategy at Novartis, Merck, Roche and others.

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Top an­a­lyst finds a sil­ver lin­ing in Ab­b­Vie’s $63B Al­ler­gan buy­out — but there’s a catch

Af­ter get­ting beat up on all sides from mar­ket ob­servers who don’t much care for the lat­est mega-deal to ar­rive in bio­phar­ma, at least one promi­nent an­a­lyst now is start­ing to like what he sees in the num­bers for Ab­b­Vie/Al­ler­gan.

But it’s go­ing to take some en­cour­age­ment if Ab­b­Vie ex­ecs want it to last.

Ab­b­Vie’s mar­ket cap de­clined $20 bil­lion on Tues­day as the stock took a 17% hit dur­ing the day. And SVB Leerink’s Ge­of­frey Porges can see a dis­tinct out­line of an up­side af­ter re­view­ing the fun­da­men­tals of the deal.

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While Ako­rn works to re­vive its for­tunes, the FDA hits it with an­oth­er warn­ing let­ter

Ako­rn just can’t dig it­self out of its hole.

The spe­cial­ty gener­ic drug­mak­er has re­ceived yet an­oth­er warn­ing let­ter from the FDA this year. With­out dis­clos­ing any specifics, the Lake For­est, Illi­nois-based drug­mak­er on Wednes­day said the US reg­u­la­tor had is­sued the let­ter, cit­ing an in­spec­tion of its Som­er­set, New Jer­sey man­u­fac­tur­ing fa­cil­i­ty in Ju­ly and Au­gust of 2018. The com­pa­ny’s shares $AKRX dipped about 1.7% to $4.65 be­fore the bell.