In­censed by Chi­na CRISPR scan­dal, US con­sor­tium am­pli­fy glob­al call to sus­pend hu­man em­bryo edit­ing

In­spired by his bi­ol­o­gist broth­er, Al­dous Hux­ley laid out his dystopi­an vi­sion — re­plete with ge­net­i­cal­ly mod­i­fied cit­i­zens strat­i­fied by an in­tel­li­gence-based so­cial hi­er­ar­chy — in his 1932 book Brave New World. The emer­gence of mi­to­chon­dr­i­al re­place­ment ther­a­py or ‘three-par­ent IVF’ and one rogue Chi­nese sci­en­tist lat­er, fears that un­bri­dled hu­man em­bryo edit­ing could be dan­ger­ous from a sci­en­tif­ic, eth­i­cal, and so­ci­etal per­spec­tive have reignit­ed. On Wednes­day, a con­sor­tium of sci­en­tists, bioethi­cists, and biotech ex­ec­u­tives wrote to US HHS sec­re­tary Alex Azar, call­ing for a col­lab­o­ra­tion on a bind­ing glob­al mora­to­ri­um on hu­man clin­i­cal germline ex­per­i­men­ta­tion.

Alex Azar

Glob­al­ly, guide­lines vary wide­ly about the ex­tent (or lack there­of) of germline re­search — in­tro­duc­ing her­i­ta­ble changes to sperm, eggs or em­bryos — is per­mit­ted. Some re­gions ban it al­to­geth­er; some al­low lab re­search but not preg­nan­cies (like in the UK); while oth­ers have no poli­cies. In the US, the NIH does not fund germline re­search, but pri­vate fund­ing is sanc­tioned.

Last month, an in­ter­na­tion­al group of ethi­cists and re­searchers, in­clud­ing ex­perts who orig­i­nal­ly de­vel­oped CRISPR–Cas9 as a gene-edit­ing tool, called for a mora­to­ri­um on clin­i­cal use of hu­man germline edit­ing un­til the safe­ty of the tech­nique has been es­tab­lished and a con­sen­sus on ac­cept­able use has been reached.

(W)e call for the es­tab­lish­ment of an in­ter­na­tion­al frame­work in which na­tions, while re­tain­ing the right to make their own de­ci­sions, vol­un­tar­i­ly com­mit to not ap­prove any use of clin­i­cal germline edit­ing un­less cer­tain con­di­tions are met.

The NIH sup­port­ed the call.

The move fol­lowed last year’s news that con­tro­ver­sial Shen­zhen-based re­searcher Jiankui He ge­net­i­cal­ly edit­ed em­bryos us­ing CRISPR/Cas9 tools — with in­ten­tion of in­duc­ing HIV re­sis­tance —  which were im­plant­ed and re­sult­ed in the birth of twin in­fant girls, trig­ger­ing a tem­pest in sci­en­tif­ic cir­cles the world over. In the wake of the scan­dal, the Chi­nese gov­ern­ment tight­ened its over­sight of gene edit­ing and oth­er “high-risk bio­med­ical tech­nolo­gies” in March.

“He pro­ceed­ed with­out clear med­ical need, in a sur­rep­ti­tious man­ner lack­ing any mean­ing­ful pub­lic or sci­en­tif­ic com­mu­ni­ty dis­cus­sion or con­sen­sus, and with­out any reg­u­la­to­ry ap­proval,” the group of 62 de­cried in the let­ter, con­demn­ing such hu­man germline clin­i­cal ex­per­i­men­ta­tion as ir­re­spon­si­ble.

Feng Zhang

“Such hu­man ge­net­ic ma­nip­u­la­tion should be con­sid­ered un­ac­cept­able and sup­port a bind­ing glob­al mora­to­ri­um un­til se­ri­ous sci­en­tif­ic, so­ci­etal, and eth­i­cal con­cerns are ful­ly ad­dressed,” the ex­perts, in­clud­ing CRISPR/Cas9 co-in­ven­tor Feng Zhang, said.

They un­der­scored a myr­i­ad of is­sues such as off-tar­get ef­fects and mu­ta­tions, which apart from the med­ical im­pact could pose ma­jor eth­i­cal con­cerns, be­cause re­search sub­jects would in­clude, and not on­ly be lim­it­ed, to em­bryos and chil­dren, but al­so fu­ture gen­er­a­tions of de­scen­dants.

Clin­i­cal germline gene edit­ing is ap­pro­pri­ate­ly pro­hib­it­ed in the Unit­ed States, across much of Eu­rope, in Chi­na, and in many oth­er coun­tries…Be­fore this sta­tus quo is re­vis­it­ed, it is vi­tal that ex­ten­sive dis­cus­sions and en­gage­ment take place among all ma­jor stake­hold­ers, in­clud­ing mem­bers of the sci­en­tif­ic, med­ical, pa­tient, care­giv­er, pol­i­cy, le­gal, eth­i­cal, and faith com­mu­ni­ties.

But the group was clear that the mora­to­ri­um should be lim­it­ed to germline edit­ing, not so­mat­ic (cells in the body ex­cept sperm and egg cells) cells, which have sig­nif­i­cant reper­cus­sions in the un­der­stand­ing and treat­ment of hu­man dis­ease.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

Vicente Anido (University of West Virginia via YouTube)

Aerie fires CEO af­ter lead pro­gram flop, com­ments about pri­ma­ry end­points be­ing 'not re­quired'

Aerie Pharmaceuticals CEO Vicente Anido has left the company less than a week after trying to chart a Phase III study in the wake of a serious Phase IIb flop.

Anido’s last day at Aerie was Friday, the biotech announced in a news release Tuesday morning, and Benjamin McGraw is taking his place in an interim role. The now former CEO was terminated without cause, according to an SEC filing.

The board has started looking for a full-time chief to take his place.

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When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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