Gene edit­ing stocks get bush­whacked as new stud­ies high­light CRISPR/Cas9 can­cer risks

Gene edit­ing stocks have a habit of run­ning up and down when some new piece of re­search un­der­scores their po­ten­tial or the risks as­so­ci­at­ed with the tech.

To­day the num­bers were plung­ing in­to the red for CRISPR Ther­a­peu­tics $CR­SP, In­tel­lia $NT­LA and Ed­i­tas $ED­IT as some top-lev­el in­ves­ti­ga­tors spot­light­ed a con­nec­tion be­tween CRISPR-Cas9 and an added risk of can­cer as­so­ci­at­ed with the tech­nol­o­gy. And soon af­ter the stud­ies hit, the biotechs in­volved be­gan to strike back at the re­searchers’ con­clu­sions.

Jus­si Taipale

The prob­lem, says Pro­fes­sor Jus­si Taipale, now at the De­part­ment of Bio­chem­istry, Cam­bridge, is that edit­ing cells with p53 is hard be­cause it ac­ti­vates a sys­tem that flags the cell for DNA dam­age. As a re­sults, there’s a nat­ur­al pref­er­ence for cells that lack the p53 path­way, which are more vul­ner­a­ble to can­cer, giv­ing rise to vul­ner­a­ble cell pop­u­la­tions. 

De­press­ing p53 ac­tiv­i­ty in cells may well have the same risks, as they are stripped of their nat­ur­al de­fens­es.

Taipale worked with in­ves­ti­ga­tors at the pres­ti­gious Karolin­s­ka In­sti­tute in Swe­den.

“Al­though we don’t yet un­der­stand the mech­a­nisms be­hind the ac­ti­va­tion of p53, we be­lieve that re­searchers need to be aware of the po­ten­tial risks when de­vel­op­ing new treat­ments,” Taipale says. “This is why we de­cid­ed to pub­lish our find­ings as soon as we dis­cov­ered that cells edit­ed with CRISPR-Cas9 can go on to be­come can­cer­ous.”

Si­mul­ta­ne­ous­ly, a group at the No­var­tis In­sti­tutes for Bio­Med­ical Re­search al­so raised the same is­sue with p53, un­der­scor­ing some of the risks in­volved with CRISPR/Cas9 tech­nol­o­gy and spook­ing in­vestors who were gam­bling that this tech­nol­o­gy will de­liv­er a whole new gen­er­a­tion of drugs.

Dar­ren Grif­fin

Dar­ren Grif­fin, a ge­net­ics ex­pert at Kent Uni­ver­si­ty who was not in­volved in ei­ther study, told Reuters that the study rais­es “rea­son for cau­tion, but not nec­es­sar­i­ly alarm”.

“Al­most any treat­ment that has the pow­er to do good, has the pow­er to do harm and this find­ing should be con­sid­ered in this broad­er con­text,” he added. “As we learn more about the CRISPR-Cas9 sys­tem and how it can be used, this study will in­evitably be con­sid­ered a sig­nif­i­cant find­ing.”

In­tel­lia was one of the first to re­spond to the re­port, and the droop­ing stock price. In an email to me the biotech not­ed:

We’ve ob­served no signs of this type of tox­i­c­i­ty or cells trans­form­ing in­to can­cer or tu­mors in In­tel­lia’s in vi­vo and ex vi­vo pro­grams.

In­tel­lia has not found this type of ef­fect in any of our in vi­vo stud­ies us­ing our lipid nanopar­ti­cle de­liv­ery sys­tem, in­clud­ing our 52-week study of suc­cess­ful TTR knock­down in mice and our on­go­ing stud­ies of non-hu­man pri­mates. For In­tel­lia’s ex vi­vo work, we have achieved ef­fi­cient edit­ing (>90 per­cent) in HSCs and T-cells and have not seen the type of tox­i­c­i­ty or tu­mor­genic­i­ty be­ing re­port­ed in these pa­pers. De­spite ex­tend­ed ob­ser­va­tion in an­i­mals and in vit­ro cul­tures, we have not seen this ef­fect. In­tel­lia’s cur­rent ap­proach­es are di­rect­ed at dif­fer­ent cell types.

CRISPR shares were down 13% Mon­day af­ter­noon, In­tel­lia was off 9% and Ed­i­tas shed 10% of its val­ue.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Build­ing on suc­cess­ful PD-1 pact, Eli Lil­ly li­cens­es di­a­betes drug to Chi­nese part­ners at In­novent

Eli Lilly is expanding its partnership with China’s Innovent in a deal involving a diabetes drug sitting in its Phase I reserves.

The two companies had jointly developed one of China’s first homegrown PD-1 agents, scoring an approval for Tyvyt (sintilimab) late last year for relapsed/refractory classical Hodgkin’s lymphoma. This time around, Lilly is out-licensing a piece of its diabetes pipeline, a leading franchise that has historically produced the top-selling Trulicity and Humalog.

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.