The End­points 100 CEO Sur­vey: Ex­ecs of­fer a big thumbs up for Got­tlieb and some sug­ges­tions for mak­ing the FDA a bet­ter agency

Scott Got­tlieb, Com­mis­sion­er of Food and Drugs, ap­pears be­fore a US Sen­ate sub­com­mit­tee to re­view the FDA’s 2018 bud­get re­quest on Tues­day, June 20, 2017

AP Im­ages / End­points News

About the worst thing that any­body in our biotech ex­ec­u­tive sur­vey group has to say about FDA Com­mis­sion­er Scott Got­tlieb right now is that it’s still ear­ly in the game for him and they’re wait­ing to see how things de­vel­op be­fore they of­fer a firm opin­ion.

Af­ter that, it’s all good.

“Look­ing across the range of ad­min­is­tra­tion nom­i­nees, I’d say FDA did ex­cep­tion­al­ly well,” writes Jeff Jonker, pres­i­dent of NGM Bio­phar­ma­ceu­ti­cals, in a note that res­onat­ed through­out the re­spons­es we col­lect­ed. “To his cred­it, Dr. Got­tlieb seems ac­tive­ly com­mit­ted to the mis­sion of the agency.”

Al­to­geth­er 74 of 88 ex­ecs in our End­points sur­vey group — 84% — gave Got­tlieb their thumbs up. The rest are stick­ing to the side­lines with a neu­tral po­si­tion — for now.

There were 0 votes crit­i­ciz­ing the pick.

The re­spons­es for our most re­cent check­up on the biotech pulse range from an ap­pre­ci­a­tion of Got­tlieb’s pro­fes­sion­al ex­pe­ri­ence to his will­ing­ness to try new things to im­prove reg­u­la­to­ry over­sight of the drug de­vel­op­ment process. And for a group of ex­ecs who are, by and large, up­set and dis­ap­prov­ing of his boss — Pres­i­dent Don­ald Trump — Got­tlieb is quick to win ku­dos for his ap­pre­ci­a­tion of sci­ence and an in­sid­er’s un­der­stand­ing of how the agency works.

Says one: “Got­tlieb is one of the few mem­bers of this ad­min­is­tra­tion that ap­pears to un­der­stand and ap­pre­ci­ate sci­ence.”

There’s al­so a clear echo from an ear­li­er de­bate over who should run the FDA, as biotech ex­ecs gen­er­al­ly heaped abuse on Jim O’Neill and his no­tion that the ef­fi­ca­cy bar should lie on the ground. You could see that in one as­sess­ment — “ex­pe­ri­enced adult” — of Got­tlieb’s strengths.

The De­moc­rats’ ma­jor ob­jec­tion to Got­tlieb that his pre­vi­ous work as an in­vestor and con­sul­tant in the field left him hope­less­ly con­flict­ed is clear­ly not shared by biotech ex­ecs — of both po­lit­i­cal per­sua­sions.

Got­tlieb’s ear­ly pop­u­lar­i­ty is just one of sev­er­al is­sues we cov­ered in our lat­est in­dus­try sur­vey. By and large this group of ex­ecs is up­beat about the fu­ture of the busi­ness and their com­pa­nies, look­ing to make more hires in an era of fair­ly ready ac­cess to cap­i­tal. The lack of M&A so far this year, though, has some grow­ing con­cerns about val­u­a­tions, pric­ing re­mains a big is­sue with no easy so­lu­tions, and while Got­tlieb is draw­ing pos­i­tive re­views, there are al­so a num­ber of sug­ges­tions on how the FDA could do bet­ter.

Want a bet­ter FDA? Hire ex­cel­lent staffers. Lots of them

Got­tlieb clear­ly has a man­date from the pres­i­dent to im­prove the FDA and find a bet­ter way to hur­ry along the reg­u­la­to­ry process, in all ar­eas out­side of on­col­o­gy, which is wide­ly viewed by the in­dus­try — and Got­tlieb — as the mod­el for all oth­er di­vi­sions in the agency. So we asked the mem­bers of the E100 what they would do dif­fer­ent­ly at the FDA, and what they would be sure to leave un­mo­lest­ed.

Arie Bellde­grun

Staffing is clear­ly an is­sue for a num­ber of the ex­ecs who com­plet­ed the sur­vey. The FDA is un­der­staffed in key ar­eas, and most want to see gener­ics pushed through faster. Biotech ex­ecs want more reg­u­la­tors, and they want bet­ter staff with more ex­per­tise in their field.

That top­ic came up re­peat­ed­ly, in dif­fer­ent ways.

Arie Bellde­grun, the CEO of Kite, now in the last leg of its reg­u­la­to­ry re­view for a ground­break­ing CAR-T treat­ment, says it would be best to leave the re­view process alone. Pos­i­tive change, he adds, will come from ex­pe­ri­enced, high­ly mo­ti­vat­ed staffers at the FDA. And he sug­gests tak­ing a leaf from the new Chi­nese play­book.


Fight for more ex­pe­ri­enced and high qual­i­ty man­pow­er to do the work and com­plete it in a time­ly man­ner. Keep your ex­am­in­ers sat­is­fied and feel­ing ac­com­plished. Learn from the Chi­nese FDA and CDE!! What a change there!! I have just re­turned from a very im­pres­sive vis­it and meet­ings with the leg­is­la­tors and ex­am­in­ers in Bei­jing. They are ex­cit­ed, en­gaged, full of en­er­gy, and have sig­nif­i­cant­ly ex­pand­ed their pro­fes­sion­al work­force. No com­plaints on be­ing short of staff or lack of great can­di­dates ( many of them trained in the US!). High­ly rec­om­mend a vis­it with them AS­AP.

There were sev­er­al bit­ing re­marks about the eteplirsen con­tro­ver­sy, with lin­ger­ing anger ev­i­dent that the agency chose to make an ex­cep­tion for Sarep­ta and its Duchenne drug. How­ev­er, it was al­so clear that there’s plen­ty of sup­port for re­spon­si­ble use of bio­mark­ers and sur­ro­gate end­points in com­ing up with faster ap­provals for many kinds of drugs, in­clud­ing those head­ed to the rare dis­ease field.

Nan­cy Si­mon­ian

Nan­cy Si­mon­ian, the CEO at Sy­ros Phar­ma­ceu­ti­cals, had this to say:

Keep the fo­cus on mov­ing in­no­v­a­tive prod­ucts swift­ly for­ward for dis­eases with high un­met need. Pro­vide more con­sis­tent guid­ance on bio­mark­er dri­ven strate­gies. Pro­mote ear­li­er ex­plo­ration of com­bi­na­tions and adap­tive tri­al de­signs to al­low more ef­fi­cient de­vel­op­ment. En­hance the per­spec­tive of the pa­tient in de­ci­sions on what con­sti­tutes clin­i­cal ben­e­fit and risk/re­ward.

From re­view­ing the sur­vey and mod­er­at­ing a re­cent con­ver­sa­tion on FDA re­form in Cam­bridge, MA, I’ll em­pha­size that there’s con­sid­er­able sup­port for mak­ing cer­tain that pa­tient per­spec­tives are re­spon­si­bly in­clud­ed in the re­view process, in­clud­ing a big­ger fo­cus on pa­tient re­port­ed out­comes in clin­i­cal tri­als.

Al­so, biotech R&D is in­creas­ing­ly less and less like­ly to be neat­ly di­vid­ed along the di­vi­sion­al bound­aries in­side the agency. That is caus­ing some added frus­tra­tion. Here’s one CEO, anony­mous­ly:

Change the di­vi­sion­al frame­work. It is an old fash­ioned way to di­vide a world that is in­creas­ing­ly mol­e­c­u­lar.

And don’t for­get about doc­tors and pa­tients, urges sci­en­tist and biotech in­vestor/en­tre­pre­neur Greg Ver­dine.

Em­pha­size the ed­u­ca­tion­al mis­sion of the FDA to help pa­tients and pre­scribers nav­i­gate the risk/ben­e­fit equa­tion for drugs.

We al­so asked CEOs about pub­lish­ing CRLs and found some sol­id back­ing for that.

Self re­straint on drug prices? It’s not enough

To be sure, there are some peo­ple in the in­dus­try who like the idea that com­pa­nies can rein in drug prices to help lance the boil on this is­sue. Up un­til a few days ago, the gen­er­al con­sen­sus was that the Trump ad­min­is­tra­tion would try some­thing de­fin­i­tive to slash drug prices. That is less and less like­ly, if the re­port­ing from Wash­ing­ton DC is ac­cu­rate. But self dis­ci­pline on pric­ing won’t be enough, ac­cord­ing to 63% of the sur­vey group.

“In­sin­cere,” re­marked one. You mean a cap of 10%? asks an­oth­er. That’s still way above in­fla­tion, say some. And the gen­er­al pub­lic won’t buy it now in any case, es­pe­cial­ly as long as a few price gougers ru­in pub­lic opin­ion about bio­phar­ma.

“The pub­lic’s per­cep­tion is now so neg­a­tive that more will be need­ed to turn it around. A few re­main­ing rot­ten ap­ples are enough to sour it for the rest.”

“I think it is a piece of the puz­zle, but on its own a com­mit­ment with­out demon­stra­ble change and ac­tion will not fun­da­men­tal­ly change the per­cep­tion. Need to keep the in­no­va­tion up and mak­ing drugs that have a big im­pact on pa­tients’ lives.”

Sev­er­al not­ed that the is­sue isn’t about drug pric­ing per se, but more about the stiff out-of-pock­et charges that are be­ing levied. As long as that re­mains in is­sue, man­u­fac­tur­ers can cut prices all they want with­out re­solv­ing the is­sue.

Sus­tain­able pric­ing? Hm­m­mm…

A sol­id ma­jor­i­ty of 60% be­lieve that the pric­ing on new drugs this year is sus­tain­able for all con­cerned. But a sig­nif­i­cant mi­nor­i­ty — 22% — said no.

Ac­cess to cap­i­tal

Close to 80% of our group in the E100 are bull­ish about ac­cess to cap­i­tal, with many rank­ing it good or ex­cel­lent.

“As an IO com­pa­ny with pos­i­tive hu­man da­ta, I feel I can get all the cap­i­tal I want.”

Oth­ers ex­pressed en­thu­si­asm about non-tra­di­tion­al cap­i­tal mak­ing it in­to the mar­ket, and sev­er­al re­marked that in this day and age in biotech, good com­pa­nies with good ideas have good ac­cess to cash.

But sev­er­al sound­ed a note of cau­tion. VCs ap­pear to be in­creas­ing­ly in­ter­est­ed on­ly in in­cu­bat­ing their own com­pa­nies, said a few, not look­ing out­side the ranks to in­vest in biotechs with lots of po­ten­tial.

And God help you if the da­ta sour — in­vestors ap­pear to be in­creas­ing­ly harsh in the face of a set­back, say some.

IPOs: Not bad, but not 2014

The biotech IPO mar­ket, which be­gan to show some fresh signs of live­li­ness af­ter the sur­vey went out, drew def­i­nite skep­ti­cism. 70% said the IPO mar­ket was av­er­age or on­ly fair. On­ly one in four thought it was good.

And there isn’t much be­lief that things will get much bet­ter in the short term, ac­cord­ing to 65%. The big boom of 2014 is def­i­nite­ly dead, said sev­er­al ex­ecs. And it’s not com­ing back soon.

Af­ter all, say some, gen­er­al­ist in­vestors are out of biotech and there are lots of fac­tors be­yond the con­trol of biotech that dic­tate in­vest­ment trends.

“The IPO mar­ket seems to be sup­port­ing high-qual­i­ty com­pa­nies, but I don’t see a re­turn to the 2014/2015 mar­ket.”

It will go up, Arc­turus CEO Joseph Payne writes: “The volatil­i­ty in­dex (VIX) has been con­sis­tent­ly sta­ble for the last 6 months (post elec­tion). This has been the my pre­ferred da­ta source as a pre­dic­tor of bub­bles pop­ping. In oth­er words, IPOs will be “the same” or “go up” as long as the VIX stays un­der 15.”

As I write this, the biotech sec­tor is ex­pe­ri­enc­ing a spike, and we’ll see how sus­tain­able it is by the time we ask this ques­tion again.

Hir­ing: Heck yes. But good tal­ent is hard to find

A big yes here. From the be­gin­ning of this sur­vey, which is now get­ting close to a year ago, these ex­ecs were in a hir­ing mode. In the lat­est round, 83% said they were adding staff in the sec­ond quar­ter; 86% will be adding staff lat­er in the year. No one is re­duc­ing staff. And that fits in with over­all in­dus­try pat­terns, where adding staff is now the name of the game.

“Both of the com­pa­nies I am build­ing are hir­ing ag­gres­sive­ly,” says one.

Brex­it, Schmex­it: “Good glob­al hir­ing in UK with no im­pact from Brex­it un­cer­tain­ties to date.”

“Mar­ket for tal­ent is get­ting very tight in San Fran­cis­co.”

“We’re hir­ing ag­gres­sive­ly but find­ing the right peo­ple is a chal­lenge with the sup­ply not keep­ing any­where near the de­mand,” notes Yu­val Co­hen.

Deal Watch: Show me the mon­ey

Talk to the av­er­age Big Phar­ma ex­ec, and you’ll get an ear­ful about how ex­pen­sive biotech val­u­a­tions are these days. Ask a biotech ex­ec, though, and things are just so-so.

More than half of the ex­ecs say that val­u­a­tions are on­ly av­er­age.

Why is that? De­spite big deals for Acte­lion and an ear­ly Ari­ad buy­out, M&A in biotech is in the slow lane. Tax re­form is still hangin­gin lim­bo and de­spite all the promis­es, we’re not see­ing any­thing like the ac­tiv­i­ty an­tic­i­pat­ed in 2017.

Right now it’s a case of “show me the mon­ey.” Once the deals and dol­lars (or eu­ros) flow, they’ll be ready to be­lieve again. In the mean­time, they’re on the side­lines with all the deal­mak­ers.

This is the third End­points 100 ex­ec­u­tive sur­vey. Pre­vi­ous sur­vey re­sults are avail­able here, and here. The End­points 100 is an in­vite-on­ly group of bio­phar­ma chief ex­ec­u­tives, polled once-a-quar­ter. 

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Martin Shkreli (Shutterstock)

Mar­tin Shkre­li con­tin­ued to or­ches­trate an­ti-com­pet­i­tive schemes for Dara­prim be­hind bars — FTC

Martin Shkreli didn’t just blog, read up on drug development news and run his biotech business with a contraband cell phone in prison. According to the FTC, he was also coordinating the anticompetitive scheme to shield Daraprim — the drug at the center of a price-gouging controversy that earned him the “Pharma Bro” nickname — from generic rivals.

Back in January the FTC, together with New York’s attorney general, launched a federal lawsuit against Shkreli, who’s now serving a 7-year sentence for defrauding investors in his hedge fund, alleging that he effectively created a drug monopoly. While Shkreli’s notorious move to raise the per tablet price of Daraprim from $17.50 to $750 was perfectly legal, the tactics he allegedly deployed to box out competitors weren’t.

Cal­lid­i­tas bets up to $102M on a biotech buy­out, snag­ging a once-failed PBC drug

After spending years developing its oral formulation of the corticosteroid budesonide, Sweden’s Calliditas now has its sights set on the primary biliary cholangitis field.

The company will buy out France-based Genkyotex, and it’s willing to bet up to €87 million ($102 million) that Genkyotex’s failed Phase II drug, GKT831, will do better in late-stage trials.

Under the current agreement, Calliditas $CALT will initially pay €20.3 million in cash for 62.7% of Genkyotex (or €2.80 a piece for 7,236,515 shares) in early October, then circle back for the rest of Genkyotex’s shares under the same terms. If nothing changes, the whole buyout will cost Calliditas €32.3 million, plus up to  €55 million in contingent rights.

James Wilson, WuXi Global Forum at JPM20

FDA puts up a red light for Pas­sage Bio’s first gene ther­a­py pro­gram, de­lay­ing a pro­gram from James Wilson's group at Penn

Gene therapy pioneer James Wilson spearheaded animal studies demonstrating the potential of new treatments injected directly into the brain, looking to jumpstart a once-and-done fix for an extraordinarily rare disease called GM1 gangliosidosis in infants. His team at the University of Pennsylvania published their work on monkeys and handed it over to Passage Bio, a Wilson-inspired startup building a pipeline of gene therapies — with an IND for PBGM01 to lead the way.

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