A fa­ther's plea: The FDA needs to make sure that Juno's lethal dis­as­ter is­n't re­peat­ed

The FDA nev­er has pub­licly ex­plained just why it de­cid­ed to lift a clin­i­cal hold on Juno’s lead CAR-T drug JCAR015 just days af­ter the stun­ning news that the tri­al was be­ing halt­ed af­ter three pa­tients tak­ing the cell ther­a­py died of a cere­bral ede­ma. But then, it nev­er does, cit­ing se­cre­cy rules that fre­quent­ly keep reg­u­la­tors silent.

Now the fa­ther of one of those vic­tims has joined in a pe­ti­tion from the Cen­ter for Re­spon­si­ble Sci­ence seek­ing some re­al trans­paren­cy at the FDA on the way it han­dles pa­tient deaths — with ma­jor im­pli­ca­tions for the peo­ple who par­tic­i­pate in clin­i­cal tri­als.

Al­most a year af­ter Michael Vokhgelt’s 24-year-old son Max died in Juno’s ROCK­ET study, and five months af­ter telling STAT that “he died for greed,” Vokhgelt is still look­ing for an­swers. Max didn’t die from leukemia, says his fa­ther. He was killed by the drug, which has since been scrapped by Juno.

Not on­ly did Juno not an­nounce Max Vokhgelt’s death, a week lat­er it put out a re­lease cit­ing the “en­cour­ag­ing” and “im­pres­sive” re­sults it was see­ing.

In the fa­ther’s words:

It wasn’t un­til two more tri­al vol­un­teers died and FDA is­sued a clin­i­cal hold that on Ju­ly 7, 2016, Juno an­nounced the deaths. Juno blamed the deaths on flu­dara­bine, a chemother­a­py pre­con­di­tion­ing treat­ment in con­junc­tion with the CAR-T ther­a­py. FDA ac­cept­ed Juno’s ex­pla­na­tion and al­lowed Juno to re­sume the tri­al with­out Flu­dara­bine. I was dev­as­tat­ed when I learned that two more tri­al par­tic­i­pants died in No­vem­ber from cere­bral ede­ma. How can this hap­pen? I don’t even know the ra­tio­nale be­hind FDA’s de­ci­sion to lift the clin­i­cal hold af­ter my son and two oth­ers died, be­cause that is con­sid­ered “pro­pri­etary”.

I have read the Cit­i­zen Pe­ti­tion from the Cen­ter for Re­spon­si­ble Sci­ence and sup­port the re­quest­ed reg­u­la­to­ry amend­ments to al­low for the use of the pre­clin­i­cal test that is best to pre­dict what will hap­pen to clin­i­cal tri­al par­tic­i­pants. If tra­di­tion­al tests don’t al­ways pre­dict dead­ly tox­i­c­i­ties, drug spon­sors must be al­lowed to use more pre­dic­tive tests that bet­ter pre­dict what hap­pens in hu­mans.

It is FDA’s re­spon­si­bil­i­ty to pro­tect hu­man health and pro­tect the pub­lic from dan­ger­ous drugs. To achieve that man­date, all avail­able tools to pre­dict safe­ty must be used. I don’t want an­oth­er fam­i­ly to go through what my fam­i­ly went through.

In a let­ter sent last April, and first re­port­ed by RAPS’ Zachary Bren­nan, the Cen­ter for Re­spon­si­ble Sci­ence not­ed 19 treat­ment-re­lat­ed deaths in clin­i­cal tri­als from Ju­ly 2016 through April 2017.  Three of those were in a study of a ri­val CAR-T by Kite, which re­cent­ly was hit with the death of its first pa­tient from a case of cere­bral ede­ma.

The CRS wants things to change be­fore more pa­tients die.

“We ar­gue that every­thing that can be done to pro­tect clin­i­cal tri­al vol­un­teers must be done. Rather than re­sume a tri­al with­out know­ing the ac­tu­al cause of the dead­ly tox­i­c­i­ty, spon­sors should have made the drug avail­able so that it could be test­ed in a hu­man-rel­e­vant plat­form.”

The FDA says it’s still un­der re­view. Let’s hope they do bet­ter by tri­al vol­un­teers.

The top 100 bio­phar­ma VCs, Bob Brad­way places $2B bet in can­cer, gene edit­ing pi­o­neer's new big idea, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Before diving in, we had some news to share: Endpoints is launching a premium weekly report focusing on all things regulatory. Coverage will be led by our new senior editor, Zachary Brennan, who joins us from POLITICO. Arsalan Arif has more details in his Publisher’s Note.

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Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Bruce Cozadd, Jazz CEO (Jazz Pharmaceuticals)

Jazz CEO Bruce Cozadd cam­paigned for 6 months to buy GW Phar­ma. A 90% pre­mi­um sealed the deal — along with $17.6M in ‘re­ten­tion’ in­cen­tives

Jazz CEO Bruce Cozadd didn’t beat around the bush.

In his first video meeting with GW Pharma chief Justin Gover last July 8, he offered to pay $172 a share to get the company, which had beaten the odds in getting its remarkable cannabinoid drug Epidiolex across the regulatory finish line for epilepsy. GW’s stock closed at $129 that day.

Cozadd had already done his homework on the financing to make sure he could swing it the way he wanted. He just needed to do some due diligence before making the non-binding bid firm.

UP­DAT­ED: Not 3 weeks af­ter tak­ing Hu­ma­cyte pub­lic, Ra­jiv Shuk­la launch­es an­oth­er blank check com­pa­ny

One of biotech’s earliest SPAC investors is back with another blank-check company, less than a month after his last effort announced its intent to merge.

Rajiv Shukla is intending to take a third lucky winner public with Alpha Healthcare Acquisition III, filing to go public Thursday with a $150 million raise penciled in. The move comes just a couple of weeks after Shukla’s second SPAC said it would jump to Nasdaq in tandem with Laura Niklason’s Humacyte in a $255 million new investment.

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How does Paul Hud­son's $13.5M comp pack­age stack up against oth­er CEOs? He's in the 'first quar­tile'

Paul Hudson arrived at Sanofi like a hurricane, chopping off duds in the pipeline, shaking up the C-suite, striking big M&A deals and jumping into the Covid-19 vaccine race — all in an attempt to reboot a pharma giant notorious for its setbacks.

Now, we’re getting a look at what the CEO brought home in his first year on the job.

When all is said and done, Hudson will have made about $6.7 million in 2020, about $2.5 million of which has already been paid. The bigger figure includes a $2.3 million bonus that’s subject to approval at an April meeting, and another $1.8 million in variable compensation that has yet to be paid.

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Af­ter three years of courtship (and turn­downs), Mer­ck pounced on the first glance of clin­i­cal da­ta in $1.85B Pan­dion takeover

It’s almost become cliché for biotech executives to talk about the importance of keeping your options open and being prepared to go all the way. But when it comes to negotiating with a giant like Merck, a little patience can indeed go a long way.

Just ask Pandion Therapeutics.

Days ago we already learned that Merck is shelling out $1.85 billion to pick up the biotech and its slate of autoimmune hopefuls. What we didn’t know until the SEC disclosure dropped Thursday is that the deal comes after Pandion turned down two other proposals from Merck over the past three years and held out until the last minute for a sweetened deal.

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Covid-19 roundup: RE­COV­ERY tri­al halts re­cruit­ment for colchicine study af­ter find­ing ‘no con­vinc­ing ev­i­dence’; Italy blocks As­traZeneca vac­cine ship­ment meant for Aus­tralia

It may be the end of the road for colchicine, an inexpensive oral anti-inflammatory drug commonly used to treat gout, as a potential Covid-19 treatment — at least in hospitalized patients.

The UK’s RECOVERY trial put out the word on Friday that it’s halting enrollment in its colchicine study after a data monitoring committee saw “no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any pre-specified subgroup.”