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.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Troy Wilson, Kura CEO

FDA lifts par­tial hold on Ku­ra's Phase Ib AML pro­gram as biotech re­dou­bles mit­i­ga­tion ef­forts

Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.

Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.

A Sen­ate bill wants to even an 'un­lev­el play­ing field' for do­mes­tic, for­eign in­spec­tion drop-ins amid back­log

Amid geopolitical tensions between the US and China, two Republican senators are calling for a bill that would aim to strike a balance on domestic and foreign inspection requirements from the FDA.

Sens. Mike Braun (R-IN) and Joni Ernst (R-IA) have penned a bill called the Creating Efficiency in Foreign Inspections Act. It contains a bit of rhetoric, highlighting “communist China” not once, but twice in the release, but states that the goal is to even the playing field between foreign and American manufacturers.

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