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.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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[via AP Images]

Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

Jason Kelly. Mike Blake/Reuters via Adobe

Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.

Jeff Kindler's Cen­trex­ion re­news bid to make pub­lic de­but

Jeffrey Kindler’s plan to take his biotech — which is developing a slate of non-opioid painkillers — public, is back on.

The Boston based company, led by former Pfizer $PFE chief Kindler, originally contemplated a $70 million to $80 million IPO last year— but eventually postponed that strategy. On Wednesday, the company revived its bid to make a public debut in a filing with the SEC — although no pricing details were disclosed.