Back­lash: Har­vard ex­perts fret over the fall­out from FDA’s OK for Sarep­ta’s con­tro­ver­sial Duchenne drug

Two of Har­vard’s top FDA pol­i­cy ex­perts, Aaron Kessel­heim and Jer­ry Avorn, have ex­pressed some deep con­cerns about the agency’s ap­proval of eteplirsen, OK’d to be sold as Ex­ondys 51 for $300,000-plus a year, and the im­pli­ca­tions for fur­ther show­downs in the near fu­ture as more de­vel­op­ers look to test the bound­aries on the agency’s stan­dards.

Writ­ing on­line in the Jour­nal of the Amer­i­can Med­ical As­so­ci­a­tion, the two re­viewed the cam­paign used to back eteplirsen, win­ning an OK with scant ev­i­dence of suc­cess in pro­duc­ing dy­s­trophin — con­trary to what Sarep­ta had claimed — a prob­lem­at­ic re­liance on his­tor­i­cal com­par­isons, and the unan­i­mous op­po­si­tion of the main re­view­ers, in­clud­ing se­nior of­fi­cials who ap­pealed Janet Wood­cock’s lone in­sis­tence on an ac­cel­er­at­ed ap­proval.

They didn’t see much mer­it in Sarep­ta’s case, and more of these con­fronta­tions are like­ly on the way now, they note. The two pol­i­cy ex­perts al­so con­clud­ed that the ap­proval threat­ens pa­tients and oth­er com­pa­nies that stuck with FDA guide­lines re­quir­ing much more rig­or­ous da­ta. They wrote:

Speed­ing drugs to mar­ket based on such bio­mark­er out­comes can ac­tu­al­ly lead to a worse out­come for pa­tients, even those with life-threat­en­ing dis­eases, if a prod­uct con­fers no mean­ing­ful ben­e­fit and car­ries a risk of ad­verse ef­fects and a high cost. Im­me­di­ate­ly af­ter ap­proval, the man­u­fac­tur­er an­nounced a price of $300,000 per year for eteplirsen. This ap­proach al­so un­fair­ly pe­nal­izes man­u­fac­tur­ers that pur­sue a more rig­or­ous course of de­vel­op­ment us­ing more clin­i­cal­ly rel­e­vant end points, while re­ward­ing com­peti­tors that sub­mit tri­als that have less ev­i­dence sup­port­ing ef­fi­ca­cy.

The ex­perts al­so raised fur­ther con­cerns about a drug that re­lied on a ve­he­ment cam­paign by pa­tient ad­vo­cates and the way in which the reg­u­la­tor should ap­proach the anec­do­tal sup­port pro­vid­ed by pa­tients and their fam­i­lies in tiny, un­con­trolled stud­ies.

Echo­ing re­marks from NYU’s Art Ca­plan, who re­cent­ly out­lined his thoughts in an in­ter­view with me, Kessel­heim and Avorn are al­so look­ing for a new ap­proach that can pro­vide a bet­ter frame­work for more such ap­provals, in­clud­ing pro­grams that of­fer these drugs at cost, rather than with a big prof­it built in.

Pa­tients with DMD need bet­ter treat­ments, and drugs like eteplirsen might one day fill that role. For now, though, the drug has pro­vid­ed a wor­ri­some mod­el for the next gen­er­a­tion of mol­e­c­u­lar­ly tar­get­ed ther­a­pies: demon­strate a slight dif­fer­ence in a lab­o­ra­to­ry test, ac­ti­vate the pa­tient com­mu­ni­ty, win ap­proval, and charge high prices, while re­ly­ing on lim­it­ed reg­u­la­to­ry fol­low-up.

The FDA’s John Jenk­ins re­cent­ly out­lined just why the FDA needs to stick with rig­or­ous de­vel­op­ment re­quire­ments, not­ing that Sarep­ta’s cam­paign was “NOT” a good mod­el for oth­ers to fol­low. But what Kessel­heim, Avorn and Ca­plan are say­ing is that the dis­cus­sion about the fall­out from the Sarep­ta de­ci­sion is just be­gin­ning, no mat­ter how much top reg­u­la­tors would like to put it be­hind the agency.

Vlad Coric (Biohaven)

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. 

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Norbert Bischofberger. Kronos

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.

Seer adds ex-FDA chief Mark Mc­Clel­lan to the board; Her­cules Cap­i­tal makes it of­fi­cial for new CEO Scott Bluestein

→ On the same day it announced a $17.5 million Series C, life sciences and health data company Seer unveiled that it had lured former FDA commissioner and ex-CMS administrator Mark McClellan on to its board. “Mark’s deep understanding of the health care ecosystem and visionary insights on policy reform will be crucial in informing our thinking as we work to bring our liquid biopsy and life sciences products to market,” said Seer chief and founder Omid Farokhzad in a statement.

Daniel O'Day

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.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a 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

ViiV Healthcare has always been something unique in the global drug industry.

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

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

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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