Genome edit­ing prod­ucts: FDA rec­om­mends at least 15 years of fol­low-up af­ter clin­i­cal tri­als

As In­tel­lia re­cent­ly un­veiled its lat­est promis­ing da­ta around one in a se­ries of po­ten­tial­ly game-chang­ing gene ther­a­pies, the FDA on Tues­day sought to fur­ther en­cour­age the field with new draft guid­ance on what should be sub­mit­ted in a clin­i­cal tri­al ap­pli­ca­tion and what po­ten­tial­ly con­cern­ing safe­ty is­sues to track for these genome edit­ing prod­ucts.

The agency is up­front about the risks of genome edit­ing, as Al­lo­gene was hit with a clin­i­cal hold and pre­clin­i­cal stud­ies sug­gest po­ten­tial risks. The draft guid­ance points to sev­er­al spe­cif­ic risks as­so­ci­at­ed with genome edit­ing, in­clud­ing off-tar­get edit­ing, un­in­tend­ed con­se­quences of on- and off-tar­get edit­ing, and the un­known long-term ef­fects of on- and off-tar­get edit­ing.

As such con­cerns linger, spon­sors may be on the hook for a long and ex­pen­sive fol­low-up to any clin­i­cal work. As part of ef­forts to fur­ther en­sure the safe­ty of such de­vel­op­ing prod­ucts, the guid­ance rec­om­mends at least 15 years of long-term fol­low-up af­ter prod­uct ad­min­is­tra­tion, which is in line with past guid­ance on gene edit­ing.

The agency al­so calls for ad­e­quate mon­i­tor­ing of any off-tar­get edit­ing and ad­e­quate as­sess­ment of the out­comes of un­in­tend­ed con­se­quences of on- and off-tar­get edit­ing.

“Ad­di­tion­al mon­i­tor­ing should cap­ture AEs re­lat­ed to aber­rant cel­lu­lar pro­lif­er­a­tion, im­muno­genic­i­ty, and tu­mori­genic­i­ty,” the agency says. “Such AEs should be an­tic­i­pat­ed from pre-clin­i­cal stud­ies, if pos­si­ble, and tox­i­c­i­ty grad­ing and man­age­ment strat­e­gy should be out­lined in the clin­i­cal pro­to­col.”

And for the small­er com­pa­nies just start­ing out, the draft of­fers a brief guide as to what to ex­pect when it comes to the type and de­gree of ge­nom­ic mod­i­fi­ca­tion, specifics on ex vi­vo vs. in vi­vo ge­nom­ic mod­i­fi­ca­tions, and how best to find the op­ti­mal de­liv­ery method for the edit­ed genes.

“When de­vel­op­ing a hu­man GE [genome edit­ing] prod­uct, we rec­om­mend that spon­sors con­sid­er: 1) the method by which the DNA se­quence change will be achieved; 2) the type of ge­nom­ic mod­i­fi­ca­tion need­ed for the de­sired ther­a­peu­tic ef­fect; and, 3) the de­liv­ery method of the hu­man GE com­po­nents,” the 17-page draft says.

On the clin­i­cal end, the agency again makes clear that due to the risky na­ture of these prod­ucts, first-in-hu­man tri­als “gen­er­al­ly should be de­signed to en­roll on­ly sub­jects for whom no oth­er treat­ment op­tions are avail­able or ac­cept­able,” but then lat­er on in the draft, the agency al­so says that “in some in­stances, sub­jects with less ad­vanced or more mod­er­ate dis­ease may be ap­pro­pri­ate for in­clu­sion in first-in-hu­man clin­i­cal stud­ies.”

As far as pre­clin­i­cal ob­jec­tives, the draft calls for spon­sors to iden­ti­fy an ad­e­quate dose range and reg­i­men, es­tab­lish the fea­si­bil­i­ty and safe­ty of the clin­i­cal route of ad­min­is­tra­tion, and iden­ti­fy po­ten­tial tox­i­c­i­ties, among a check­list of items to com­plete.

Mean­while, in ad­di­tion to the genome edit­ing guid­ance, the FDA on Tues­day al­so re­leased new, 36-page draft guid­ance on de­vel­op­ing CAR-T prod­ucts.

The FDA of­fers CMC, pre­clin­i­cal and clin­i­cal rec­om­men­da­tions for those de­vel­op­ing CAR-T prod­ucts, as well as gen­er­al con­sid­er­a­tions on CAR con­structs, vec­tor, cel­lu­lar start­ing ma­te­r­i­al, and more.

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Dave Marek, Myovant CEO

My­ovant board balks as ma­jor­i­ty own­er Sum­it­o­mo swoops in with a $2.5B deal to buy them out

Three years after Sumitomo scooped up Roivant’s 46% stake in the publicly traded Myovant $MYOV as part of a 5-company, $3 billion deal, they’re coming back for the whole thing.

But these other investors at Myovant want more than what the Japanese pharma company is currently offering to pay at this stage.

Sumitomo is bidding $22.75 a share for the outstanding stock, which now represents 48% of the company after Sumitomo bumped its ownership since the original deal with Roivant. Myovant, however, created a special committee on the board, and they’re shaking their heads over the offer.

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Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Vlad Coric, Biohaven CEO

Vlad Coric charts course for new Bio­haven with neu­ro­science push and Big Phar­ma vets on board

What’s Biohaven without its CGRP portfolio? That’s what CEO Vlad Coric is tasked with deciding as he maps out the new Biohaven post-Pfizer takeover.

Pfizer officially scooped up Biohaven’s CGRP assets on Monday, including blockbuster migraine drug Nurtec and the investigational zavegepant, for $11.6 billion. As a result, Coric spun the broader pipeline into an independent company on Tuesday — with the same R&D team behind Nurtec but about 1,000 fewer staffers and a renewed focus on neuroscience and rare disease.

In AstraZeneca's latest campaign, wild eosinophils called Phils personify the acting up often seen in uncontrolled asthma

As­traZeneca de­buts an­noy­ing pur­ple ‘Phil’ crea­tures, per­son­i­fied asth­ma eosinophils ‘be­hav­ing bad­ly’

There are some odd-looking purple creatures lurking around the halls of AstraZenca lately. The “Phil” character cutouts are purple, personified eosinophils with big buggy eyes and wide mouths, and they’re a part of AZ’s newest awareness effort to help people understand eosinophilic asthma.

The “Asthma Behaving Badly” characters aren’t only on the walls at AZ to show the new campaign to employees, however. The “Phils” are also showing up online on the campaign website, and in digital and social ads and posts on Facebook and Instagram.

Kite Phar­ma gets FDA to sign off on new Cal­i­for­nia-based vec­tor man­u­fac­tur­ing fa­cil­i­ty

Kite Pharma just got FDA approval to kick off operations at a new manufacturing campus.

The cancer-focused, CAR-T cell therapy player made the announcement Monday, saying that the federal regulatory agency gave the green light to Kite’s 100,000 square-foot, retroviral vector manufacturing facility in Oceanside, CA.

Kite’s global head of technical operations Chris McDonald tells Endpoints News that the facility has been in the works for about four years, after Kite teamed up with its parent company Gilead. Gilead acquired Kite Pharma for just shy of $12 billion in 2017.

Big Phar­ma heavy­weights seek tweaks to FDA's clin­i­cal out­come as­sess­ment guid­ance

Pfizer, GSK, Janssen, Regeneron, Boehringer Ingelheim and at least a half dozen other companies are calling on the FDA to provide significantly more clarity in its draft guidance from this summer on clinical outcome assessments, which are a type of patient experience.

The draft is the third in a series of four patient-focused drug development guidance documents that the FDA had to create as part of the 21st Century Cures Act, and they describe how stakeholders (patients, caregivers, researchers, medical product developers and others) can collect and submit patient experience data and other relevant information for medical product development and regulatory decision-making.

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Robert Califf, FDA commissioner (via AP Images)

User fees in ac­tion: FDA un­veils new short­ened sup­ple­ment re­view, rare dis­ease pi­lots

Thanks to PDUFA VII, signed into law last Friday by President Joe Biden, the FDA this week unveiled two new industry-friendly pilot programs to advance new rare disease endpoints via additional meetings, and to shorten FDA review times for supplemental apps aimed at unmet medical needs.

The agency this week released eagerly-awaited details behind the shortened pilot, known as the Split Real Time Application Review or STAR pilot program, which will speed up certain FDA reviews of efficacy supplements across all therapeutic areas (thanks to earlier submissions of data), but only for those that propose addressing an unmet medical need.

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Mar­ket­ingRx roundup: No­var­tis re­cruits NFL coach for Leqvio cam­paign; Pfiz­er pro­motes ‘Sci­ence’ merch on so­cial me­dia

Novartis is turning to a winning coach to talk about Leqvio and the struggles of high cholesterol — including his own. Bruce Arians, the retired NFL head coach of the Arizona Cardinals and Super Bowl-winning Tampa Bay Buccaneers, is partnering with the pharma for its “Coaching Cholesterol” digital, social and public relations effort.

In the campaign, Arians talks about the potential for “great comebacks” in football and heart health. Once nicknamed a “quarterback whisperer,” he is now retired from fulltime coaching (although still a front-office consultant for Tampa Bay), and did a round of media interviews for Novartis, including one with People and Forbes.

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