Prothena’s lead drug NEOD001 just im­plod­ed in 2 late-stage stud­ies — and there’s noth­ing left to sal­vage

Prothena’s lead drug has de­ci­sive­ly failed a cru­cial Phase IIb study for rare, sec­ond-line cas­es of AL amy­loi­do­sis. And af­ter con­clud­ing that their Phase III for front­line use is al­so head­ed to fail­ure, the biotech’s ex­ec­u­tive team is scrap­ping the whole pro­gram.

Gene Kin­ney

In a pre­view of the re­sults be­ing re­leased this morn­ing for one of the most close­ly watched cat­a­lysts of Q2, Prothena $PR­TA CEO Gene Kin­ney said the com­pa­ny faced a very dif­fi­cult de­ci­sion, and had on­ly one re­al op­tion.

“We are a sci­ence-led com­pa­ny,” Kin­ney told me. “I’m a sci­en­tist my­self.” And when you’re up against some­thing like this, he said, you have to “pay at­ten­tion to the da­ta and take the most ap­pro­pri­ate steps for­ward.”

It’s not pret­ty, and there will be no hunt for sil­ver lin­ings for a drug once reck­oned as a po­ten­tial block­buster worth around $1.5 bil­lion in peak sales. There will be no at­tempt to re­vive the ef­fort.

Prothena’s shares dropped 62% Mon­day morn­ing. And as an­a­lysts’ bleak as­sess­ments hit, things got even worse. By mid-af­ter­noon the stock was down near­ly 70%, wip­ing out close to a bil­lion dol­lars in mar­ket cap af­ter start­ing the day at $1.4 bil­lion.

“We’ve had a large set­back here with this pro­gram,” says the CEO, who is turn­ing to re­view “the most op­ti­mal way of mov­ing for­ward…All of us at Prothena had gen­uine­ly hoped that we had a drug that would help pa­tients suf­fer­ing from this dis­ease.”

Neil Wood­ford

Right now, Prothena plans to bring the Phase III to an end as they look over the fi­nal da­ta. But there’s no ques­tion in Kin­ney’s mind that the tri­als had foundered, with the Phase IIb de­liv­er­ing noth­ing sta­tis­ti­cal­ly sig­nif­i­cant on the pri­ma­ry or sec­ondary end­points. 

Some of those end­points slight­ly fa­vored the drug, oth­ers slight­ly fa­vored the place­bo.

The haz­ard ra­tio in the Phase III tri­al was at 0.84 when they de­cid­ed to drop the ef­fort at the rec­om­men­da­tion of the in­de­pen­dent mon­i­tor­ing board.

The pri­ma­ry end­point of the Phase IIb PRON­TO study was a mea­sure­ment of car­diac best re­sponse us­ing the high­ly re­gard­ed bio­mark­er for NT-proB­NP as a like­ly sur­ro­gate for sur­vival. Prothena had told in­vestors and an­a­lysts that a suc­cess here could trig­ger a re­quest for ac­cel­er­at­ed ap­proval at the FDA. 

“This is the worst case sce­nario for this pro­gram un­for­tu­nate­ly for PR­TA at this time,” not­ed Jef­feries an­a­lyst Michael Lee.

The re­sults will be a par­tic­u­lar­ly bit­ter pill for Neil Wood­ford to swal­low. The UK in­vestor bet heav­i­ly on Prothena’s suc­cess with NEOD001, reg­u­lar­ly of­fer­ing his en­thu­si­as­tic en­dorse­ment of the com­pa­ny and the team in charge. Now he’ll have to ac­count for an­oth­er painful set­back on the port­fo­lio, af­ter the stock falls far be­low what he paid to buy in.

The bru­tal­ly bad news for in­vestors comes on the heels of a sig­nif­i­cant step for­ward for Prothena. The biotech re­cent­ly signed a rich, pre­clin­i­cal li­cens­ing deal with Cel­gene to beef up its fledg­ling neu­ro­sciences pipeline — with $150 mil­lion in cash tied to it — in­clud­ing an Alzheimer’s pro­gram for tau.

That ef­fort will take the spot­light, along with an­oth­er clin­i­cal pro­gram and the pre­clin­i­cal work un­der way on oth­er drugs.

AL amy­loi­do­sis is a rare con­di­tion that’s di­ag­nosed in about 3,000 peo­ple a year in the US, though it may al­so well be un­der­diag­nosed, ac­cord­ing to Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter. In the dis­ease, rogue plas­ma cells pro­duce an im­munoglob­u­lin light-chain pro­tein that pro­duces amy­loid, which is de­posit­ed in or­gans and gums the works, ca­pa­ble of se­vere dam­age. 

As there are no drugs ap­proved for the con­di­tion, doc­tors of­ten turn to au­tol­o­gous stem cell trans­plants fol­low­ing chemother­a­py to erad­i­cate the er­rant plas­ma cells. Treat­ment al­so some­times in­volved mul­ti­ple myelo­ma drugs like Vel­cade, with ev­i­dence that carfil­zomib and dara­tu­mum­ab can tamp down on the pro­duc­tion of the plas­ma cells. There are a va­ri­ety of stud­ies now in the clin­ic for myelo­ma drugs in this con­di­tion, but any ded­i­cat­ed drug that can mod­i­fy the dis­ease will find a big mar­ket.

Prothena’s share­hold­ers have had a lot to fret about on this de­vel­op­ment pro­gram. The com­pa­ny’s chief med­ical of­fi­cer, Sarah Noon­berg, abrupt­ly re­signed in Feb­ru­ary — less than a year af­ter the Bio­Marin vet joined Prothena — which in­evitably spurred some buzz on Twit­ter. More sig­nif­i­cant­ly, Sahm Ad­ran­gi’s Ker­ris­dale of­fered up one of their Nas­daq SWAT at­tacks on the drug and the com­pa­ny.

Ker­ris­dale set the chances of suc­cess in these tri­als at 0%.

“Prothena’s car­diac best re­sponse rate is mere­ly a byprod­uct of well-doc­u­ment­ed nat­ur­al vari­ance,” Ker­ris­dale not­ed, “and we be­lieve there is no chance of NEOD001 pro­duc­ing sta­tis­ti­cal­ly sig­nif­i­cant re­sults in its cur­rent Phase 2b and Phase 3 tri­als.”

Next up for Prothena is their ex­per­i­men­tal Parkin­son’s drug, PRX002/RG7935, which is al­lied with Roche. It is their on­ly oth­er clin­i­cal stage pro­gram, fol­low­ing a de­ci­sion last fall to scrap a pro­gram for PRX003. 

Kin­ney says an­oth­er pre­clin­i­cal pro­gram will soon be ad­vanced in­to hu­man stud­ies, and there’s plen­ty of cash on hand. The biotech, which had 125 staffers on hand at the end of 2017, al­so list­ed $422 mil­lion in cash — lat­er aug­ment­ed with Cel­gene’s $150 mil­lion buy-in.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Ken Frazier, AP Images

Why Mer­ck wait­ed, and what they now bring to the Covid-19 fight

Nicholas Kartsonis had been running clinical infectious disease research at Merck for almost 2 years when, in mid-January, he got a new assignment: Searching the Pharma giant’s vast libraries for something that could treat the novel coronavirus.

The outbreak was barely two weeks old when Kartsonis and a few dozen others got to work, first in small teams and then in a larger task force that sucked in more and more parts of the sprawling company as Covid-19 infected more and more of the globe. By late February, the group began formally searching for vaccine and antiviral candidates to license. Still, while other companies jumped out to announce their programs and, eventually and sometimes controversially,early glimpses at human data, Merck remained silent. They made only a brief announcement about a data collection partnership in April and mentioned vaguely a vaccine and antiviral search in their April 28 earnings call.

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Mark Genovese (Stanford via Twitter)

Gilead woos fil­go­tinib clin­i­cal in­ves­ti­ga­tor from Stan­ford to lead the charge on NASH, in­flam­ma­to­ry dis­eases

With an FDA OK for the use of filgotinib in rheumatoid arthritis expected to drop any day now, Gilead has recruited a new leader from academia to lead its foray into inflammatory diseases.

Mark Genovese — a longtime Stanford professor and most recently the clinical chief in the division of immunology and rheumatology — was the principal investigator in FINCH 2, one of three studies that supported Gilead’s NDA filing. In his new role as SVP, inflammation, he will oversee the clinical development of the entire portfolio.

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Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Bris­tol My­ers Squib­b's just-launched MS drug Zeposia makes the cut in key ul­cer­a­tive col­i­tis tri­al

In March, Zeposia became the third oral S1P modulator to secure US approval for multiple sclerosis. Now, the drug has succeeded in a key ulcerative colitis study.

The immunomodulator, akin to others in its class, controls lymphocyte trafficking by limiting the white blood cells to the lymphatic system, in the lymph nodes, and thwarting their ability to jam up lymph nodes — precluding their ability to penetrate the bloodstream and the central nervous system.

No­var­tis chips in $10M for IPO-bound part­ner Pli­ant; Tenax shares soar on heart drug da­ta

Novartis is coming in with $10 million to help support the looming IPO of a partner. Pliant Therapeutics posted a new filing with the SEC showing that Novartis is buying the shares at $15, the mid-point of the range. It’s adding several million shares to the offering, bringing the total to around $135 million. Biotech companies have been enjoying quite a run on virtual Wall Street, with investors boosting new offerings to some big hauls.

Stephen Isaacs, Aduro president and CEO (Aduro)

Once a high fly­er, a stag­ger­ing Aduro is auc­tion­ing off most of the pipeline as CEO Stephen Isaacs hands off the shell to new own­ers

After a drumbeat of failure, setbacks and reorganizations over the last few years, Aduro CEO Stephen Isaacs is handing over his largely gutted-out shell of a public company to another biotech company and putting up some questionable assets in a going-out-of-business sale.

Isaacs —who forged a string of high-profile Big Pharma deals along the way — has wrapped a 13-year run at the biotech with one program for kidney disease going to the new owners at Chinook Therapeutics. A host of once-heralded assets like their STING agonist program partnered with Novartis (which dumped their work on ADU-S100 after looking over weak clinical results), the Lilly-allied cGAS-STING inhibitor program and the anti-CD27 program out-licensed to Merck will all be posted for auction under a strategic review process.

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Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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