Top 10 pipeline blowups, set­backs and sna­fus in H1 2016

Some years you have to stretch a bit to find a line­up of 10 no­table set­backs in the pipeline. In the first half of this year, I could have done one in each quar­ter and had a few left over for the dis­hon­or­able men­tion col­umn.

What we have here is a col­lec­tion of grue­some self-in­flict­ed wounds, more ev­i­dence that the home run swing looks good on pa­per and ter­ri­ble in ex­e­cu­tion and a new cat­e­go­ry: the drug that post­ed pos­i­tive da­ta but looked bad com­pared to the com­pe­ti­tion.

You can mark that last one in red; it will be back in fu­ture lists. Get­ting pos­i­tive da­ta against a place­bo or an old­er stan­dard of care is less and less like­ly to cut it. More and more con­tenders will need to be com­pared in­stant­ly against ri­vals in the pipeline. And with ex­pec­ta­tions run­ning high in fields like can­cer, more an­a­lysts (though not all) are go­ing to be mak­ing some re­al de­mands.

No doubt you’ll be think­ing of oth­er set­backs that didn’t make the list. And there were some doozies. J&J walked away from its an­ti-NGF pain drug ful­ranum­ab with bare­ly a nod of the head. No­var­tis’ “break­through” mus­cle drug bima­grum­ab failed a key study. Aduro’s com­bo failed a key test. Es­pe­ri­on was evis­cer­at­ed af­ter it told in­vestors that the FDA was chang­ing course on its tri­al de­mands.

So it goes.

Drug de­vel­op­ment is a tough field. Just ask the fol­low­ing com­pa­nies.

 


1. Clo­vis On­col­o­gy  rocile­tinib

CEO Patrick Ma­haffy

Boul­der, CO
$CLVS

CEO: Patrick Ma­haffy

The prob­lem: Clo­vis On­col­o­gy billed its lead-up to the sub­mis­sion for rocile­tinib as an Olympic dive. For play­ing a di­rect role in turn­ing the dive in­to a world-class bel­ly flop, the biotech wins the top spot as H1’s biggest im­plo­sion.

Clo­vis watch­ers will re­mem­ber that the com­pa­ny once played ri­val to As­traZeneca’s Tagris­so (9291). But then the FDA called them out on some sus­pi­cious tu­mor re­spons­es and a slew of con­firmed hits had to be trad­ed for miss­es. Its stock col­lapsed, FDA in­sid­ers could bare­ly con­ceal their dis­taste and the com­pa­ny lost a con­sid­er­able amount of rep along with the bulk of its mar­ket cap.

Ro­ci was quick­ly buried and now no men­tion is made of it — even when the FDA’s PDU­FA date rolled around June 28 with­out so much as a 2-sen­tence SEC fil­ing to mark the for­mal re­jec­tion.

Cur­rent­ly un­der in­ves­ti­ga­tion by the feds, Clo­vis is now ramp­ing up a new ef­fort to back ru­ca­parib, which finds it­self in yet an­oth­er late-stage horse race with se­ri­ous com­pe­ti­tion. Fail­ure here is not an op­tion, but it’s a very re­al pos­si­bil­i­ty.


2. As­traZeneca — ZS-9/treme­li­mum­ab

CEO Pas­cal So­ri­ot

Lon­don
$AZN

CEO: Pas­cal So­ri­ot

The prob­lems: You don’t pay $2.7 bil­lion for a hy­per­kalemia drug that’s await­ing reg­u­la­to­ry ac­tion at the FDA, tell every­one you’re go­ing to make more than a bil­lion dol­lars a year off of it and then get hand­ed a re­jec­tion with­out hav­ing a few red faces to show for it.

As­traZeneca says it won’t have to run a new tri­al for ZS-9, but it does have some ex­plain­ing to do about man­u­fac­tur­ing that was se­ri­ous enough to war­rant a CRL. As­traZeneca is a Big Phar­ma in a hur­ry, though, and caught up in a bid­ding war it bar­reled in­to a set­back.

ZS-9 is now like­ly on hold un­til around the end of the year or ear­ly 2017 as Re­lyp­sa’s ri­val Veltas­sa con­tin­ues to make progress on the mar­ket. Yet to be de­cid­ed: Which of these drugs will have the most fa­vor­able safe­ty pro­file, though ZS-9 still has sev­er­al ad­vo­cates on its side.

As­traZeneca, mean­while, al­so had to ex­plain a so­lo set­back for the CT­LA-4 drug treme­li­mum last Feb­ru­ary. A top prospect at As­traZeneca, the drug failed a Phase IIb tri­al for mesothe­lioma af­ter in­ves­ti­ga­tors re­cruit­ed 571 pa­tients for the test.


3. Bio­Marin  dris­apersen

San Rafael, CA
$BM­RN

CEO: Jean-Jacques Bi­en­aimé

The prob­lem: Bio­Marin paid $680 mil­lion to get dris­apersen in its buy­out of Pros­en­sa. But that big gam­ble end­ed up be­ing more than a com­plete write-off.

First, the FDA re­ject­ed the drug, which had al­ready failed a Phase III in the hands of Glax­o­SmithK­line, which quick­ly washed its hands of the drug and walked away. Then the EMA said no as well, and Bio­Marin not on­ly jet­ti­soned the lead drug, the com­pa­ny deep-sixed three fol­low-up ther­a­pies it was work­ing with in Phase II.

The com­pa­ny’s in­ves­ti­ga­tors couldn’t get any­where with their ar­gu­ment that there was a treat­ment strat­e­gy that could help boys af­fect­ed by the lethal dis­ease. The out­side and in­side ex­perts at the FDA gave that dis­cus­sion short shrift. Now the R&D group is go­ing back to the draw­ing board as Sarep­ta pre­pares to see if it can sur­vive an at­tempt at an ac­cel­er­at­ed ap­proval.


4. Alk­er­mes — ALKS-5461

CEO Richard Pops

Dublin
$ALKS

CEO Richard Pops

The prob­lem: A few weeks be­fore the read­out on the first two stud­ies for ALKS-5461 hit in Jan­u­ary, CEO Richard Pops called it a pend­ing “seis­mic” event.

And how.

The first six months of this year was no time to dis­ap­point in­vestors grap­pling with a bear mar­ket for biotech stocks. Alk­er­mes learned that les­son the hard way when its de­pres­sion drug failed two stud­ies and the mar­ket quick­ly re­lieved it of $4 bil­lion in mar­ket cap.

The rea­son de­vel­op­ers have three or four Phase III stud­ies for a de­pres­sion drug is be­cause they are like­ly to fail. One af­ter an­oth­er has been done in by the place­bo ef­fect, but Alk­er­mes be­lieved that it had an edge with a nov­el new tri­al de­sign aimed at thwart­ing that out­come. So two down means the drug is dead, right?

Not quite. The com­pa­ny came up with some post hoc rea­sons to be­lieve they were still on to some­thing and some an­a­lysts be­lieve that a pos­i­tive read­out for the third study could yet sal­vage the sit­u­a­tion. But it’s a nar­row, dan­ger­ous path to be trav­el­ing at this stage.

Alk­er­mes’ stock has been mak­ing a come­back since the com­pa­ny was blast­ed, but it’s been a slow climb.


5. In­fin­i­ty Phar­ma­ceu­ti­cals — du­velis­ib

CEO Ade­lene Perkins

Cam­bridge, MA
$IN­FI

CEO Ade­lene Perkins

The prob­lem: Some­times even a sta­tis­ti­cal win can be a big los­er. Case in point: Du­velis­ib.

A few weeks ago their lead drug hit the pri­ma­ry end­point in the Phase II study for in­do­lent non-Hodgkin lym­phoma, and its part­ner Ab­b­Vie quick­ly fold­ed its tent, dis­missed their $250 mil­lion up­front part­ner­ing pay­ment and hit the streets.

It was good, but just not good enough con­sid­er­ing the com­pe­ti­tion.

In­fin­i­ty suf­fered a thump­ing on Wall Street, but af­ter back-to-back re­struc­tur­ings that cost 146 jobs (for­mer “cit­i­zen-own­ers”) the com­pa­ny says it can work things out in its fa­vor. Perkins, top sci­en­tist Ju­lian Adams and every­one else still in for the ride can earn a re­ten­tion bonus for stay­ing on board. But af­ter three strikes for three top drugs, some may start to ques­tion why they still have the bat.


6. Celldex — Rin­te­ga rindopepimut

Hamp­ton, NJ
$CLDX

CEO: An­tho­ny Maruc­ci

Can­cer vac­cines have had a woe­ful record over the last cou­ple of years. Celldex added an­oth­er dose of dis­as­ter af­ter its try with Rin­te­ga proved so in­ef­fec­tive at treat­ing glioblas­toma the in­de­pen­dent mon­i­tors sug­gest­ed that in­ves­ti­ga­tors go ahead and pull the plug on the piv­otal study last March.

The over­all sur­vival rate ac­tu­al­ly fa­vored the con­trol arm over the drug.

This was a drug that had in­spired con­sid­er­able con­fi­dence from the Phase II, which some in­vestors thought should have been good enough to fu­el an at­tempt at an ac­cel­er­at­ed ap­proval. Some an­a­lysts were al­so let down at the time.

Celldex has sev­er­al da­ta read­outs com­ing up. It’s in bad need of good news.


7. PTC Ther­a­peu­tics — Translar­na ataluren

CEO Stu­art Peltz

South Plain­field, NJ
$PTCT

CEO Stu­art Peltz

The prob­lem: The FDA doesn’t of­ten refuse to file an ap­pli­ca­tion, but it made an ex­cep­tion for PTC.

PTC gets some cred­it for ad­mit­ting that the agency said it didn’t have the da­ta need­ed for an ap­proval of Translar­na (ataluren), which pos­si­bly wasn’t too sur­pris­ing as their drug had failed a mid-stage and piv­otal study for Duchenne mus­cu­lar dy­s­tro­phy.

Reg­u­la­tors have carved out a spe­cial sta­tus for ex­per­i­men­tal drugs that treat Duchenne, though. That helps ex­plain why the Eu­ro­peans gave it a con­di­tion­al ap­proval two years ago and still have done noth­ing af­ter the lat­est set­back. Even NICE is ne­go­ti­at­ing over what it will pay to cov­er the drug, while it has gath­ered sig­nif­i­cant ev­i­dence that the drug doesn’t work well at all.

PTC may have thought that same reg­u­lar­i­ty gen­eros­i­ty would ex­tend to Wash­ing­ton DC. But that was wrong.


8. Io­n­is Phar­ma­ceu­ti­cals — IO­N­IS-TTRR

CEO Stan­ley Crooke

Carls­bad, CA
$IONS

CEO Stan­ley Crooke

The prob­lem: Io­n­is changed its name from Isis to put a lit­tle dis­tance be­tween it­self and the no­to­ri­ous ter­ror­ist group. But late­ly, it’s been ter­ror­iz­ing in­vestors with a safe­ty haz­ard on its lead an­ti­sense pro­gram.

Io­n­is CEO Stan­ley Crooke took the lead role in the dra­ma, ex­plain­ing dur­ing a call with an­a­lysts in May that their drug – at high dos­es — had been linked to per­plex­ing low platelet counts in pa­tients. That caused the FDA to trig­ger a clin­i­cal hold on a pro­gram, spurring Glax­o­SmithK­line to put a planned Phase III on a back burn­er.

Rather than re­as­sure in­vestors, Crooke seemed on­ly to make mat­ters steadi­ly worse on his call, de­clin­ing to an­swer some ques­tions, such as whether any pa­tients had died. He pled for more time, but in­vestors are im­pa­tient with un­cer­tain­ty and fear.

Fur­ther com­pli­cat­ing Io­n­is’ po­si­tion is its close com­pe­ti­tion with Al­ny­lam, which was boost­ed on the tra­vails of its ri­val.


9. Ab­b­Vie — Ro­va-T

CEO Richard Gon­za­lez

North Chica­go, IL
$AB­BV

CEO: Richard Gon­za­lez

The prob­lem: Ab­b­Vie is de­vel­op­ing a rep­u­ta­tion as an undis­ci­plined buy­er. And you can put much of that down to Ro­va-T now.

Ab­b­Vie paid $5.8 bil­lion in cash to buy Stem­cen­trx, large­ly based on the promise of the lit­tle-known can­cer drug, which plays along a path­way for stem cells. And it has promised $4 bil­lion more in mile­stones.

But at AS­CO the pre­lim­i­nary da­ta for small cell lung can­cer showed a one-month sur­vival ad­van­tage over his­tor­i­cal trends, caus­ing more than a few an­a­lysts to do a dou­ble take on the drug and the deal. Ab­b­Vie can still turn this around, but the pub­lic de­but of this drug turned in­to a prat­fall.


10. Reg­u­lus — RG-101

CEO Paul Grint

La Jol­la, CA
$RGLS

CEO: Paul Grint

The prob­lem: Reg­u­lus got start­ed nine years ago as a promis­ing joint ven­ture of Al­ny­lam and Io­n­is, which you passed in the num­ber eight spot on this list. Now in the lead up to its 10th an­niver­sary, the com­pa­ny is faced with a fresh clin­i­cal hold on its lead pro­gram.

The biotech’s whole rea­son for be­ing cen­ters on its mi­croR­NA tech. The plat­form led it to a drug, RG-101, that is billed as a po­ten­tial one-time treat­ment for he­pati­tis C. It’s al­so now been linked to two cas­es of jaun­dice, which trig­gered the hold.

The reg­u­la­to­ry ac­tion raised all sorts of thorny is­sues for the com­pa­ny, in­clud­ing why it would have a top pipeline drug in a field where sev­er­al new cures dom­i­nate the field. Even if RG-101 turns out to be a suc­cess, it would still face tough com­pe­ti­tion. (There is no tougher com­peti­tor than Gilead, which al­ways plays to win.)

He­pati­tis C is al­so a huge mar­ket with mil­lions of po­ten­tial pa­tients, of course, but that al­so means the reg­u­la­to­ry bar on safe­ty is high. And now it has to face these tra­vails with a bad­ly beat­en down stock price.

That’s not a pret­ty pic­ture.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Paul Hudson, Sanofi CEO (ROMUALD MEIGNEUX/Sipa via AP Images)

Sanofi and Am­gen are bring­ing cash to cov­er the ta­ble stakes for the Hori­zon M&A game

With the market cap on Horizon Therapeutics $HZNP pushed up to the $23 billion mark today, one of the Big Pharmas in the hunt for a major league buyout deal signaled it’s playing the M&A game with cash.

Paris-based Sanofi, where CEO Paul Hudson has been largely focused on some risky biotech acquisitions to win some respect for its future pipeline prospects, issued a statement early Friday — complying with rule 2.12 of the Irish takeover rules — making clear that while the certainty or size of an offer can’t be determined, any offer “will be solely in cash.” And Amgen CEO Robert Bradway came right in behind him, filing a statement on the London Stock Exchange overnight that any offer they may make will “likely” be in cash as well.

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Matt Gline, Roivant Sciences CEO (Photo by John Sciulli/Getty Images for GLG)

Pfiz­er and Roivant team up again for an­oth­er 'Van­t', set­ting up an­ti-in­flam­ma­to­ry show­down with Prometheus

Pfizer and Roivant are teaming up to launch a new ‘Vant’ aimed at bringing a mid-stage anti-inflammatory drug to market, the pair announced Thursday.

There’s no name for the startup yet, nor are there any employees. Thus far, the new company and Roivant can be considered “one and the same,” Roivant CEO Matt Gline tells Endpoints News. But Pfizer is so enthusiastic about the target that it elected to keep 25% of equity in the drug rather than take upfront cash from Roivant, Gline said.

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Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

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SQZ Biotech slash­es head­count by 60% as founder/CEO hits ex­it — while Syn­log­ic lays off 25%

It’s a tough time for early-stage companies developing highly promising, but largely unproven, new technologies.

Just ask SQZ Biotechnologies and Synlogic. The former is bidding farewell to its founder and CEO and slashing the headcount by 60% as it pivots from its original cell therapy platform to a next-gen approach; the latter — a synthetic biology play founded by MIT’s Jim Collins and Tim Lu — is similarly “optimizing” the company to focus on lead programs. The resulting realignment means 25% of the staffers will be laid off.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and DN­Di aim to elim­i­nate sleep­ing sick­ness in Africa with promis­ing Ph II/III re­sults for new drug

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting: