Am­i­cus’ lat­est pos­i­tive up­date on Pompe drug hints at ac­cel­er­at­ed ap­proval pitch

In the lat­est twist for what’s proved to be a year-long mar­ket thriller of dra­mat­ic ups and downs, Am­i­cus Ther­a­peu­tics CEO John Crow­ley to­day peeled the cov­ers off an up­dat­ed — and up­beat — look at how their drug ATB200/AT2221 per­formed in a Phase I/II study of Pompe dis­ease. And he’s hint­ing that the pos­i­tive re­sults could pave the way to an ac­cel­er­at­ed ap­proval — pro­vid­ed reg­u­la­tors are en­cour­ag­ing.

The key take­aways on this rare dis­ease drug, Am­i­cus’ $FOLD third clin­i­cal-stage pro­gram:

John Crow­ley

Af­ter post­ing mean ini­tial im­prove­ments in a 6-minute walk test af­ter 6 months of 38 me­ters and 52 me­ters for two groups of pa­tients who had ei­ther been switched from en­zyme re­place­ment ther­a­py or had nev­er had ERT, the ex­pand­ed group of pa­tients now evalu­able has re­set those num­bers at 35 me­ters and 42 me­ters. The 9-month da­ta on a se­lect group of pa­tients is com­ing in now at 37 me­ters and 75 me­ters (for two ERT-naive pa­tients).

Some ero­sion from the first set of re­sults isn’t like­ly to dull an­a­lysts’ en­thu­si­asm for the drug, while the 9-month da­ta un­der­score the kind of snap­shot on dura­bil­i­ty they’ll def­i­nite­ly like. But there was no con­trol group for this study.

Am­i­cus’ shares jumped 21% on the news.

Leerink’s Joseph Schwartz has been an en­thu­si­as­tic ob­serv­er. He not­ed:

The main ques­tion on in­vestors’ minds will be whether Am­i­cus will be able to file for reg­u­la­to­ry ap­proval based on these re­sults. Re­call, reg­u­la­tors have good ex­po­sure to Pompe dis­ease thanks to My­ozyme/Lu­mizyme, so while the Ph.1/2 study is not pbo.-con­trolled and is small in en­roll­ment, ATB200/AT2221 could be an­oth­er in­stance where­in the FDA ex­er­cis­es flex­i­bil­i­ty to ex­pe­dite ap­proval of a su­pe­ri­or drug in a pt. pop­u­la­tion with an un­met need.

It’s still ear­ly days for a small study in­volv­ing a rare dis­ease, but Am­i­cus is al­so tout­ing ev­i­dence of im­proved strength among the sub­jects in the study. And re­searchers high­light­ed im­prove­ments in bio­mark­ers of mus­cle strength to make their case that they’re right on track.

Forced vi­tal ca­pac­i­ty — a mea­sure of pul­monary func­tion — im­proved mar­gin­al­ly for the ERT-naive group, ris­ing 4.2% and 5% at 6 and 9 months, while the ERT-switch pa­tients saw a slight de­cline.

“Very con­sis­tent­ly,” Am­i­cus CEO Crow­ley tells me, “they seemed to be get­ting much stronger. I don’t know where the num­bers will specif­i­cal­ly end up,” he adds, “but the mag­ni­tude of the im­prove­ment is re­al­ly dra­mat­ic.”

The 6-minute walk test has been the cen­ter of at­ten­tion among an­a­lysts, but Crow­ley says that physi­cians have spent just as much time look­ing at the bio­mark­ers.

“These weren’t ex­pect­ed to get bet­ter,” says Crow­ley, who cre­at­ed No­vazyme to de­vel­op an ERT for Pompe dis­ease months af­ter his daugh­ter Megan was di­ag­nosed with the dis­ease as an in­fant. Gen­zyme lat­er bought out No­vazyme and Crow­ley went on to found Am­i­cus, which set out to find a bet­ter ther­a­py.

Right now the base case as­sump­tion is that the com­pa­ny will go ahead with a planned Phase III study next year, adds Crow­ley, stop­ping short of say­ing that the com­pa­ny would push for a quick OK on the Phase I/II da­ta. But he adds that com­pa­ny ex­ecs will take the ear­ly-stage da­ta to reg­u­la­tors and see what they think about pur­su­ing a short­er path to an ap­proval.

“The key (to ac­cel­er­at­ed ap­proval) is man­u­fac­tur­ing,” he adds. “We’ve in­vest­ed enor­mous sums in scale up” to pro­vide Phase III and com­mer­cial quan­ti­ties of the drug. And he be­lieves that’s put them in a good po­si­tion with reg­u­la­tors, if they prove amenable.

Am­i­cus and its in­vestors have been through a roller coast­er ride over the past year. The FDA spurned its ap­pli­ca­tion for its lead drug mi­gala­s­tat, de­mand­ing a new tri­al, even as Eu­ro­pean reg­u­la­tors pro­vid­ed a green light. Then Don­ald Trump was elect­ed pres­i­dent, and af­ter a lit­tle one-on-one lob­by­ing by Crow­ley the FDA — now un­der Scott Got­tlieb — told them they could go ahead and re-ap­ply with­out the new study.

All that speaks pos­i­tive­ly of their odds in case they do shoot for a quick ap­proval. But the year has al­so had its set­backs.

Just a few weeks ago, Am­i­cus’ drug SD-101 failed a Phase III study, miss­ing the co-pri­ma­ry and key sec­ondary end­points in treat­ing epi­der­mol­y­sis bul­losa.

A hit here will en­cour­age more in­vestors that there’s more wins than loss­es to fo­cus on — giv­ing Am­i­cus a help­ing hand as it winds its way through some cru­cial piv­otal mile­stones.

Mark Roberts, the prin­ci­pal in­ves­ti­ga­tor in the Pompe study, said:

“I be­lieve that the re­sults from this Phase 1/2 clin­i­cal study show strik­ing im­prove­ments in func­tion­al mea­sures and key bio­mark­ers dur­ing the first six months of treat­ment, in ad­di­tion to con­tin­ued, fur­ther ben­e­fit out to nine months. I am es­pe­cial­ly in­trigued by the six-minute walk dis­tance and oth­er mo­tor func­tion tests in the ERT-switch pa­tients who his­tor­i­cal­ly have de­clin­ing mo­tor func­tion fol­low­ing two or more years of treat­ment. These clin­i­cal da­ta are com­pelling and sug­gest that ATB200/AT2221 has the po­ten­tial to shift the treat­ment par­a­digm for Pompe dis­ease.”


Im­age: Megan Crow­ley, daugh­ter of Am­i­cus CEO John Crow­ley, is rec­og­nized dur­ing Pres­i­dent Don­ald Trump’s first ad­dress to a joint ses­sion of Con­gress on Feb­ru­ary 28, 2017. At 15 months old, Crow­ley was di­ag­nosed with Pompe Dis­ease and not ex­pect­ed to live more than a few short years. Megan, age 20, is now a sopho­more at Notre Dame. Chris Kle­po­nis / AP Im­ages

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In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors. 

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Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

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Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

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No­var­tis hands off 3 pre­clin­i­cal pro­grams to the an­tivi­ral R&D mas­ters at Gilead

Gilead CEO Daniel O’Day’s new task hunting up a CSO for the company isn’t stopping the industry’s dominant antiviral player from doing pipeline deals.

The big biotech today snapped up 3 preclinical antiviral programs from pharma giant Novartis, with drugs promising to treat human rhinovirus, influenza and herpes viruses. We don’t know what the upfront is, but the back end has $291 million in milestones baked in.

Vas Narasimhan, AP Images

On a hot streak, No­var­tis ex­ecs run the odds on their two most im­por­tant PhI­II read­outs. Which is 0.01% more like­ly to suc­ceed?

Novartis CEO Vas Narasimhan is living in the sweet spot right now.

The numbers are running a bit better than expected, the pipeline — which he assembled as development chief — is performing and the stock popped more than 4% on Thursday as the executive team ran through their assessment of Q2 performance.

Year-to-date the stock is up 28%, so the investors will be beaming. Anyone looking for chinks in their armor — and there are plenty giving it a shot — right now focus on payer acceptance of their $2.1 million gene therapy Zolgensma, where it’s early days. And CAR-T continues to underperform, but Novartis doesn’t appear to be suffering from it.

So what could go wrong?

Actually, not much. But Tim Anderson at Wolfe pressed Narasimhan and his development chief John Tsai to pick which of two looming Phase III readouts with blockbuster implication had the better odds of success.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

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Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

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Dokomajilar notes:

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Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

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