Albert Bourla (Evan Vucci, AP Images)

Amid safe­ty con­cerns, FDA grants two new JAK ap­provals — but with added warn­ings and a key la­bel change

Af­ter a post-mar­ket­ing tri­al for Pfiz­er’s Xel­janz turned up con­cern­ing safe­ty re­sults at the be­gin­ning of the year, thwart­ing the whole JAK class, the FDA is fi­nal­ly rolling out some new ap­provals — but with added warn­ings and a key la­bel change.

Both Xel­janz and Ab­b­Vie’s Rin­voq got cleared for new in­di­ca­tions on Tues­day, but on one con­di­tion: They can on­ly be tak­en af­ter a pa­tient has failed on one or more tu­mor necro­sis fac­tor (TNF) block­ers, like Hu­mi­ra or En­brel.

Ear­li­er this month, the FDA slapped boxed warn­ings on the la­bels of Xel­janz, Rin­voq and Eli Lil­ly’s Olu­mi­ant, flag­ging the risk of car­dio­vas­cu­lar events such as heart at­tack or stroke in high-risk pa­tients who are 50 years and old­er, es­pe­cial­ly those with oth­er risk fac­tors such as cur­rent or past smok­ers.

Xel­janz is now ap­proved for adults with ac­tive anky­los­ing spondyli­tis, a rare type of arthri­tis that caus­es pain and stiff­ness in the spine. And Rin­voq pulled a win in adults with ac­tive pso­ri­at­ic arthri­tis, a type of in­flam­ma­to­ry arthri­tis that caus­es joint pain, stiff­ness and swelling.

The lat­est fall­out over JAK safe­ty be­gan back in Jan­u­ary, when Xel­janz failed a six-year post-mar­ket­ing safe­ty study across 4,362 rheuma­toid arthri­tis pa­tients. Re­searchers found that those who re­ceived ei­ther a low or high dose of Xel­janz ex­pe­ri­enced more ma­jor car­dio­vas­cu­lar events — such as stroke and heart at­tack — than those on Hu­mi­ra or En­brel. They al­so had high­er rates of can­cer, with Pfiz­er fail­ing to hit non-in­fe­ri­or­i­ty on both pri­ma­ry end­points.

The study re­newed some dif­fi­cult ques­tions for JAK in­hibitors more broad­ly, a class that gen­er­at­ed sig­nif­i­cant ef­fi­ca­cy in au­toim­mune con­di­tions but faced re­peat­ed safe­ty con­cerns.

In the first week of De­cem­ber, the FDA con­clud­ed that there’s an in­creased risk of se­ri­ous heart-re­lat­ed events such as heart at­tack or stroke, can­cer, blood clots and death as­so­ci­at­ed with Xel­janz, and put up­dat­ed warn­ings on that drug and two oth­ers. Al­though Olu­mi­ant and Rin­voq hadn’t been stud­ied in large safe­ty tri­als, reg­u­la­tors de­cid­ed that they may pose sim­i­lar risks, as they share the same mech­a­nism of ac­tion.

In­vestors were mut­ed on the news of Ab­b­Vie and Pfiz­er’s new ap­provals, with the com­pa­ny’s stock, $AB­BV and $PFE, up about 1% in pre-mar­ket trad­ing on Tues­day.

The Xel­janz ap­proval is based on da­ta from a Phase III tri­al, show­ing that twice-dai­ly 5 mg dos­es of the block­buster drug helped 56.4% of pa­tients achieve an im­prove­ment of at least 20% on the As­sess­ment in Spondy­loArthri­tis in­ter­na­tion­al So­ci­ety scale (ASAS20), com­pared to just 29.4% of place­bo pa­tients (p<0.0001).

Just over 40% of pa­tients on Xel­janz achieved an ASAS40 re­sponse, com­pared to 12.5% on place­bo, ac­cord­ing to Pfiz­er. The safe­ty pro­file was sim­i­lar to that in ap­proved in­di­ca­tions of rheuma­toid arthri­tis and pso­ri­at­ic arthri­tis, the com­pa­ny said.

Mean­while, Rin­voq helped pso­ri­at­ic arthri­tis pa­tients treat­ed with 15 mg dos­es achieve high­er ACR50 re­spons­es (an im­prove­ment of at least 50% on the Amer­i­can Col­lege of Rheuma­tol­ogy scale) com­pared to place­bo in two Phase III tri­als. In the tri­als, 38% and 32% of pa­tients on Rin­voq achieved ACR50, com­pared to 13% and 5% on place­bo, re­spec­tive­ly.

The Rin­voq arms al­so boast­ed 16% and 9% ACR70 re­spons­es, com­pared to 2% and 1% in the place­bo arms, re­spec­tive­ly. And the drug was seen to sig­nif­i­cant­ly in­hib­it the pro­gres­sion of struc­tur­al joint dam­age com­pared to place­bo, ac­cord­ing to Ab­b­Vie. The com­pa­ny said Rin­voq’s safe­ty pro­file was con­sis­tent with that in pa­tients with rheuma­toid arthri­tis.

Now, we’ll wait to see if the added warn­ings af­fect the drugs’ per­for­mances. Xel­janz pulled in $2.4 bil­lion in 2020, and Rin­voq was a bit be­hind it with $731 mil­lion in net sales.

Alexander Lefterov/Endpoints News

A new can­cer im­munother­a­py brings cau­tious hope for a field long await­ing the next big break­through

Bob Seibert sat silent across from his daughter at their favorite Spanish restaurant near his home in Charleston County, SC, their paella growing cold as he read through all the places in his body doctors found tumors.

He had texted his wife, a pediatric intensive care nurse, when he got the alert that his online chart was ready. Although he saw immediately it was bad, many of the terms — peritoneal, right iliac — were inscrutable. But she was five hours downstate, at a loud group dinner the night before another daughter’s cheer competition.

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In a set­back, FDA or­ders Gilead to hit the brakes on their late-stage, $5B can­cer play

Gilead’s $5 billion drug magrolimab has run into a serious setback.

The FDA ordered Gilead to halt enrollment on their studies of the drug in combination with azacitidine after investigators reports revealed an “apparent imbalance” in the suspected unexpected serious adverse reactions between study arms.

“While no clear trend in the adverse reactions or new safety signal has been identified by Gilead at this time, the partial clinical hold is being implemented by Gilead across all ongoing magrolimab and azacitidine (Vidaza) combination studies worldwide in the best interests of patients as additional data is gathered and analyzed to address the concerns raised by FDA,” the big biotech said in a statement.

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Graphic: Alexander Lefterov for Endpoints News

Small biotechs with big drug am­bi­tions threat­en to up­end the tra­di­tion­al drug launch play­book

Of the countless decisions Vlad Coric had to make as Biohaven’s CEO over the past seven years, there was one that felt particularly nerve-wracking: Instead of selling to a Big Pharma, the company decided it would commercialize its migraine drug itself.

“I remember some investors yelling and pounding on the table like, you can’t do this. What are you thinking? You’re going to get crushed by AbbVie,” he recalled.

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Mar­ket­ingRx roundup: Pfiz­er de­buts Pre­vnar 20 TV ads; Lil­ly gets first FDA 2022 pro­mo slap down let­ter

Pfizer debuted its first TV ad for its Prevnar 20 next-generation pneumococcal pneumonia vaccine. In the 60-second spot, several people (actor portrayals) with their ages listed as 65 or older are shown walking into a clinic as they turn to say they’re getting vaccinated with Prevnar 20 because they’re at risk.

The update to Pfizer’s blockbuster Prevnar 13 vaccine was approved in June, and as its name suggests is a vaccine for 20 serotypes — the original 13 plus seven more that cause pneumococcal disease. Pfizer used to spend heavily on TV ads to promote Prevnar 13 in 2018 and 2019 but cut back its TV budgets in the past two fall and winter seasonal spending cycles. Prevnar had been Pfizer’s top-selling drug, notching sales of just under $6 billion in 2020, and was the world’s top-selling vaccine before the Covid-19 vaccines came to market last year.

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Roy Baynes, Merck

FDA bats back Mer­ck’s ‘pipeline in a prod­uct,’ de­mands more ef­fi­ca­cy da­ta

Despite some heavy blowback from analysts, Merck execs maintained an upbeat attitude about the market potential of its chronic cough drug gefapixant. But the confidence may be fading somewhat today as Merck puts out news that the FDA is handing back its application with a CRL.

Dubbed by Merck’s development chief Roy Baynes as a “pipeline in a product” with a variety of potential uses, Merck had fielded positive late-stage data demonstrating the drug’s ability to combat chronic cough. The drug dramatically reduced chronic cough in Phase III, but so did placebo, leaving Merck’s research team with a marginal success on the p-value side of the equation.

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Albert Bourla (Photo by Steven Ferdman/Getty Images)

UP­DAT­ED: Pfiz­er fields a CRL for a $295M rare dis­ease play, giv­ing ri­val a big head start

Pfizer won’t be adding a new rare disease drug to the franchise club — for now, anyway.

The pharma giant put out word that their FDA application for the growth hormone therapy somatrogon got the regulatory heave-ho, though they didn’t even hint at a reason for the CRL. Following standard operating procedure, Pfizer said in a terse missive that they would be working with regulators on a followup.

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UP­DAT­ED: FDA slams Eli Lil­ly's 'mis­lead­ing' In­sta­gram ad for its type 2 di­a­betes in­jec­tion

In a first for 2022, the FDA’s Office of Prescription Drug Promotion has issued an untitled letter, which was recently sent to Eli Lilly over what the agency calls a “misleading” and “particularly concerning” Instagram ad the company posted for its type 2 diabetes drug Trulicity.

The questionable Instagram post, which has since been deleted by Lilly, failed to adequately communicate the indication and limitations of use associated with Trulicity, FDA says.

US re­stricts use of two mon­o­clon­al an­ti­bod­ies that don't work against Omi­cron

Two monoclonal antibody combos from Eli Lilly and Regeneron are no longer authorized in the US, and shipments to states have ceased because HHS said they are “highly unlikely” to work against the sweeping new variant Omicron.

The move by the FDA comes as states like Florida have become insistent that the mAbs need to be independently evaluated, although the federal Department of Health and Human Services, which has shipped hundreds of thousands of these two mAbs to states in recent weeks, did not ship any this week.

Florida Gov. Ron DeSantis (AP Photo/Wilfredo Lee, File)

Opin­ion: Flori­da is so mAb crazy, Ron De­San­tis wants to use mAbs that don't work

Florida Gov. Ron DeSantis is trying so hard to politicize the FDA and demonize the federal government that he entered into an alternate universe on Monday evening in describing a recent FDA action to restrict the use of two monoclonal antibody, or mAb, treatments for Covid-19 that don’t work against Omicron.

Without further ado, let’s break down his statement from last night, line by line, adjective by adjective.