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.

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

Up­dat­ed: As­traZeneca jumps deep­er in­to cell ther­a­py 2.0 space with $320M biotech M&A

Right from the start, the execs at Neogene had some lofty goals in mind when they decided to try their hand at a cell therapy that could tackle solid tumors.

Its founders have helped hone a new approach that would pack in multiple neoantigen targets to create a personalized TCR treatment that would not just make the leap from blood to solid tumors, but do it with durability. And they managed to make their way rapidly to the clinic, unveiling their first Phase I program for advanced tumors just last May.

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Emily Leproust, Twist Bioscience CEO

Twist Bio­science’s 'fac­to­ry of the fu­ture' in Ore­gon could de­liv­er with com­pet­i­tive pric­ing, SVB Se­cu­ri­ties says

The synthetic DNA manufacturer Twist Bioscience has given a peek behind the curtain to several analysts into its “factory of the future” as well as insight into the cost structure, workflow and technology at the site.

The 110,000-square-foot manufacturing site in the city of Wilsonville, OR, just south of Portland, which was announced back in 2020, will double Twist’s production capacity and bring around 400 jobs to the area.

Lex­i­con slams FDA over hear­ing de­nial fol­low­ing a CRL for its SGLT2 in­hibitor can­di­date

Lexicon Pharmaceutical is not giving up on its Type I diabetes candidate, despite FDA’s repeated rejections. This week the company laid out is argument again for a hearing on sotagliflozin in response to the FDA’s most recent denial.

The issue goes back to March 2019 when the FDA made very clear to Lexicon and its now departed partner Sanofi that it would not approve their application for a potential Type I diabetes drug because it does not appear to be safe.

Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and DN­Di aim to elim­i­nate sleep­ing sick­ness in Africa with promis­ing Ph II/III re­sults for new drug

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting:

Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

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Digital render of CPI's Medicines Manufacturing Innovation Centre in Glasgow, Scotland (Image:

CPI opens the doors to a new $100M+ man­u­fac­tur­ing fa­cil­i­ty in Scot­land

A manufacturing site that has received interest and investments from large pharma companies and the UK government is opening its doors in Scotland.

The manufacturer CPI (Centre for Process Innovation) has opened a new £88 million ($105 million) “Medicines Manufacturing Innovation Centre” in Glasgow, Scotland, to accelerate the development of manufacturing tech and solve longstanding challenges in medicine development and manufacturing.

Pro­tect­ing its megablock­buster, Janssen chal­lenges Am­gen's Ste­lara biosim­i­lar ahead of planned 2023 launch

Johnson & Johnson unit Janssen on Wednesday sued Amgen over the company’s proposed biosimilar to its megablockbuster Stelara (ustekinumab), after Amgen said it was ready to launch next May or as soon as the FDA signs off on it.

If Amgen carries through with that plan, Janssen told the Delaware district court that the Thousand Oaks, CA-based company will infringe on at least two Janssen patents.