Sekar Kathiresan, Verve Therapeutics CEO

Verve re­veals let­ter from FDA that lays out con­di­tions to lift base edit­ing tri­al hold

We now know why Verve’s lead can­di­date was placed on hold last month by US reg­u­la­tors.

In an SEC fil­ing, Verve laid out the FDA’s con­di­tions for lift­ing the hold on its lead ther­a­py, VERVE-101. That in­cludes sub­mit­ting pre­clin­i­cal da­ta about po­ten­cy dif­fer­ences in hu­man ver­sus non-hu­man cells, risks of gene edit­ing germline cells, and off-tar­get analy­ses in non-he­pa­to­cyte cell types.

The FDA al­so wants clin­i­cal da­ta from the on­go­ing Heart-1 tri­al, and to mod­i­fy the tri­al pro­to­col in the US to add ad­di­tion­al con­tra­cep­tive mea­sures and in­crease the length of a stag­ger­ing in­ter­val be­tween the dos­ing of par­tic­i­pants.

The goal of the ther­a­py is to per­ma­nent­ly turn off the PC­SK9 gene in pa­tients with an in­her­it­ed dis­ease that caus­es ex­treme­ly high cho­les­terol lev­els.

Verve said in the fil­ing that it plans to “sub­mit a re­sponse as ex­pe­di­tious­ly as pos­si­ble” the FDA. The biotech al­so said that it is con­tin­u­ing to en­roll pa­tients for the tri­al in the UK and in New Zealand — and plans to re­port ini­tial da­ta from the dose-es­ca­la­tion part of the tri­al lat­er this year.

Verve de­clined to com­ment to End­points News out­side of the fil­ing.

The rev­e­la­tions of the FDA’s asks are the newest de­vel­op­ment that Verve an­nounced since its base edit­ing tri­al got put on hold just last month. A Phase Ib tri­al in­ves­ti­gat­ing VERVE-101 kicked off in Ju­ly as the biotech start­ed dos­ing pa­tients in New Zealand and the UK.

The lead can­di­date, a sin­gle base ed­i­tor, is be­ing test­ed in pa­tients with het­erozy­gous fa­mil­ial hy­per­c­ho­les­terolemia (HeFH). The tri­al is the first time that base edit­ing has been done in hu­mans. Base edit­ing, a genome edit­ing tech­nol­o­gy, works dif­fer­ent­ly than tra­di­tion­al CRISPR, us­ing a chem­i­cal process to change a spe­cif­ic let­ter in the tar­get gene — rather than mak­ing a dou­ble-strand­ed cut in DNA.

In­vestors did not ap­pear hap­py with the re­sults, as $VERV took an 18% dive on the Nas­daq Mon­day morn­ing.

Verve is the third biotech to have got­ten reg­u­la­to­ry per­mis­sion to ed­it genes in hu­mans di­rect­ly, thanks to New Zealand reg­u­la­to­ry au­thor­i­ties in May. In­tel­lia and Ed­i­tas Med­i­cines were the first two com­pa­nies to have got­ten the go-ahead.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

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I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

CBER Director Peter Marks (Susan Walsh/AP Images)

FDA ad­vi­so­ry com­mit­tee votes unan­i­mous­ly in fa­vor of bi­va­lent Covid shots re­plac­ing pri­ma­ry se­ries

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all current vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

The vote marks an effort to clear up confusion around varying formulations and dosing schedules for current primary series and booster vaccines, as well as “get closer to the strains that are circulating,” according to committee member Paul Offit, professor of pediatrics at the Children’s Hospital of Philadelphia.

FDA re­ports ini­tial 'no sig­nal' for stroke risk with Pfiz­er boost­ers, launch­es con­comi­tant flu shot study

The FDA hasn’t detected any potential safety signals, including for stroke, in people aged 65 years and older who have received Pfizer’s bivalent Covid booster, one senior official told members of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Thursday.

The update comes as the FDA and CDC investigate a “preliminary signal” that may indicate an increased risk of ischemic stroke in older Americans who received Pfizer’s updated shot.

FDA cuts off use for As­traZeneca’s Covid-19 ther­a­py Evusheld

The FDA has stopped use of another drug as a result of the new coronavirus variants. On Thursday, the agency announced that AstraZeneca’s antibody combo Evusheld, which was an important prevention option for many immunocompromised people and others, is no longer authorized.

The FDA said it made its decision based on the fact that Evusheld works on fewer than 10% of circulating variants.

Evusheld was initially given emergency authorization at the end of 2021. However, as Omicron emerged, so did studies that showed Evusheld might not work against the dominant Omicron strain. In October, the FDA warned healthcare providers that Evusheld was useless against the Omicron subvariant BA.4.6. It followed that up with another announcement earlier this month that it did not think Evusheld would work against the latest Omicron subvariant XBB.1.5.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.