Penn team-biotech col­lab­o­ra­tion high­lights promise of gene edit­ing in tar­get­ing PC­SK9, liv­er dis­eases

James Wil­son. Penn News

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PC­SK9 car­dio drugs may still be hav­ing a tough time build­ing a mar­ket among stub­born pay­ers, but they’re nev­er­the­less con­sid­ered a re­mark­able ad­vance in slash­ing lev­els of LDL in at-risk pa­tients. And now one of the pi­o­neers in gene ther­a­py — work­ing in col­lab­o­ra­tion with an up­start biotech com­pa­ny — has com­plet­ed a pri­mate study to show that a unique gene edit­ing ap­proach can hit the same tar­get, with pos­i­tive ef­fects.

We know through ex­ten­sive hu­man stud­ies that a drug that in­hibits the PC­SK9 pro­tein will low­er LDL, the bad cho­les­terol that’s a cul­prit in car­dio de­te­ri­o­ra­tion. James Wil­son at Penn, whose ad­vances and set­backs in gene ther­a­py helped birth the field, used a meganu­cle­ase de­vel­oped at Pre­ci­sion Bio­sciences in Durham, NC, put the en­zyme in an AAV vec­tor, and dis­patched it to the liv­er, where it tar­get­ed PC­SK9 to good ef­fect.

Us­ing a vec­tor that’s al­ready demon­strat­ed its safe­ty in hu­man he­mo­phil­ia stud­ies, the re­search team at Penn con­clud­ed that their ap­proach re­duced PC­SK9 lev­els by 45% to 84%, cut­ting LDL lev­els by 30% to 60%, “both clin­i­cal­ly rel­e­vant and sta­ble re­duc­tions. Mol­e­c­u­lar analy­ses of biop­sied liv­er tis­sue al­so demon­strat­ed that genome edit­ing in­duced mu­ta­tions in 40% to 65% of the PC­SK9 genes.”

Lili Wang

“Most of­ten these pa­tients are treat­ed with re­peat­ed in­jec­tions of an an­ti­body to PC­SK9,” said first au­thor Lili Wang, a re­search as­so­ciate pro­fes­sor of med­i­cine. “But, our study shows that with suc­cess­ful genome edit­ing, pa­tients who can­not tol­er­ate in­hibitor drugs might no longer need this type of re­peat treat­ment.”

Suc­cess here al­so points to the promise of gene edit­ing in a range of liv­er meta­bol­ic dis­eases be­yond hy­per­c­ho­les­terolemia, they note. A range of star­tups have been us­ing new gene edit­ing tech­niques, with the first for­ays in hu­mans un­der­way at Penn and in sev­er­al hos­pi­tals in Chi­na.

This is the sec­ond time in just a mat­ter of days that Pre­ci­sion has made a splash. The biotech just wrapped a whop­ping $110 mil­lion crossover round with a broad syn­di­cate of back­ers. The crew al­so split off its ag op­er­a­tions in­to a sep­a­rate com­pa­ny, like­ly flag­ging that the CEO has an S-1 in his brief­case.

An­i­mal stud­ies in the field, though, haven’t al­ways been so suc­cess­ful. Wil­son trig­gered safe­ty alarms when he re­port­ed ear­ly this year that one of his vec­tor-de­liv­ered gene ther­a­py stud­ies us­ing three rhe­sus macaque mon­keys and three pigs ran in­to a tox­ic dis­as­ter.

Four days af­ter one of the macaques had re­ceived 2×1014 GC/kg AAVhu68 vec­tor ex­press­ing hu­man SMN, the mon­key ex­pe­ri­enced a se­vere cri­sis, go­ing in­to shock af­ter suf­fer­ing se­vere liv­er dam­age, which forced re­searchers to eu­th­a­nize the pri­mate. The two oth­er macaques sur­vived, but al­so suf­fered a tox­ic re­ac­tion.

All three piglets treat­ed with a high, sys­temic IV dose were al­so eu­th­a­nized, with the first ex­pe­ri­enc­ing atax­ia and the oth­er two re­spond­ing with neu­ro­log­i­cal symp­toms.

Daniel O'Day [via AP Images]

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Daniel O’Day is executing his first major development deal since taking over as CEO of Gilead $GILD. And he’s going in deep to ally himself with a longstanding partner.

O’Day announced today that he is spending $5 billion in cash to add new late-stage drugs to Gilead’s pipeline, picking up rights to Galapagos’ $GLPG Phase III IPF drug GLPG1690 alongside adoption of the biotech’s Phase IIb drug GLPG1972 for osteoarthritis. And Gilead is also putting billions more on the table for milestones, gaining options for everything else in Galapagos’ pipeline, with a shot at all rights outside of Europe.

Altogether, Gilead is gaining rights to 6 clinical-stage assets, 20 preclinical programs and everything else being hatched in translation.

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UP­DAT­ED: Am­gen, No­var­tis scrap Alzheimer's stud­ies — is BACE fi­nal­ly dead or will Bio­gen and Ei­sai car­ry on?

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After the market closed Thursday, Amgen and Novartis announced that they were dumping two pivotal programs underway with the Banner Alzheimer’s Institute on their BACE drug CNP520 (umibecestat) after an independent review of the data indicated that patients’ cognitive abilities were actually worsening at a faster pace than the placebo arm.

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Christi Shaw at JP Morgan 2019. Jeff Rumans for Endpoints News

Fresh out of Eli Lil­ly, Christi Shaw sur­faces as Daniel O'­Day's new CEO at CAR-T pi­o­neer Kite

Well, that didn’t take long. 

We found out Thursday evening that Christi Shaw has given up her top post as the head of the Bio-Medicines group at Eli Lilly for the helm at CAR-T pioneer Kite. New Gilead CEO Daniel O’Day, a Roche veteran, had made finding a Kite CEO a top priority on his arrival at Gilead. And he went right for a headliner.

O’Day was clearly excited about the coup.

“We conducted an extensive search for a new leader at Kite and we believe that Christi’s unique set of skills will allow us to continue to build on our leadership position in cell therapy,” he said in a prepared statement. “Christi’s vast experience across complex therapeutic areas, and particularly in oncology, will serve Kite very well. She is clearly a leader who will bring teams and individuals together and I am confident she will build upon the entrepreneurial spirit at Kite as we seek to help more people with cancer around the world.”

Christi Shaw at JP Morgan 2019. Jeff Rumans for Endpoints News

Eli Lil­ly's Christi Shaw bows out of top post at the Bio-Med­i­cines unit

Less than 3 years after Eli Lilly CEO David Ricks recruited Novartis vet Christi Shaw to run their big Bio-Medicines business, she’s out.

In a statement put out Thursday morning, Lilly said that Shaw’s last day will come at the end of August. Patrik Jonsson, currently president and general manager of Lilly Japan, will succeed Shaw once he gets the paperwork sorted out.

Lilly’s shares dropped 4% on the news.

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Alnylam chief John Maraganore says that CFO Manmeet S. Soni is leaving in the proverbial pursuit of new opportunities. And he’s being replaced by ex-Shire CFO Jeff Poulton, not long after the Takeda takeover obliterated that position.

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President Donald Trump at State of the Union. AP Images

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So what exactly is the White House’s plan to tackle rising drug prices? It doesn’t look like we will get definitive answers anytime soon. On the heels of President Donald Trump’s surprise revelation that an executive order is in the works to implement a “favored nations clause,” his administration is now putting out word that it has abandoned an earlier proposal to overhaul rebates.

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Janet Woodcock, AP Images

The FDA's Janet Wood­cock talks about some big changes she's push­ing for in drug de­vel­op­ment, and agency re­views

Janet Woodcock is perhaps the most influential regulator at the FDA. And when the head of CDER talks about the changes being made at the agency when it comes to clinical trial designs, or the need to reorganize for a specific disease arena, an assessment of the expansion of gene therapy or I/O, common development mistakes, and so on, you can be sure the industry pays attention to every word.

So it was with some eagerness that I opened up Geoffrey Porges’ summary of their recent conversation about the FDA. And I wasn’t disappointed. In a wide-ranging exchange with the SVB Leerink analyst, Woodcock discussed the growing importance of patient-reported outcomes in clinical trials, a campaign underway now to see if CROs would help spur more basket studies to compare drugs head-to-head, and much, much more.

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Ex-DARPA di­rec­tor pur­sues all-in-one can­cer pill as NED CEO; Karyopharm los­es com­mer­cial chief ahead of drug roll­out

“Why not try?”

That’s what Geoffrey Ling told me over the phone when asked about what led him to his journey to the position of CEO at NED Biosciences — a company with a lofty goal of creating an all-in-one oral drug to treat all types of cancer and making this drug available to not only developed nations, but also the developing world. 

Ling comes from an extensive background in medicine and the government. He is the co-leader of The Brain Health Project, a professor of neurology and an attending neurocritical care physician at John Hopkins University and Hospital, as well as the assistant director for Medical Innovation of the Science Division in president Obama’s White House Office of Science and Technology Policy (OSTP).