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.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

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Joe Wiley, Amryt Pharma CEO

Am­ryt Phar­ma sub­mits a for­mal dis­pute res­o­lu­tion to the FDA over re­ject­ed skin dis­ease drug

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

Sen. Thom Tillis (R-NC) (J. Scott Applewhite/AP Images)

Phar­ma-friend­ly sen­a­tor calls on FDA for a third time to show patent pro­tec­tions should­n't be blamed for high drug prices

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”

AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

FDA un­veils new draft guid­ance to help with oligonu­cleotide ther­a­peu­tics de­vel­op­ment

While oligonucleotides, a wide variety of synthetically modified RNA or RNA/DNA hybrids that bind to a target RNA sequence to alter RNA and/or protein expression, have been winning approvals in recent years (e.g. Novartis’ cholesterol drug Leqvio), the regulatory agency is offering new draft guidance for those looking to follow a similar path.

The non-binding guidance, titled “Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics Guidance for Industry” deals with pharmacokinetic, pharmacodynamic, and safety assessments required as part of oligonucleotide therapeutics R&D.

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Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

EMA signs off on 3 drugs re­cent­ly re­ject­ed by FDA, in­clud­ing Bio­Mar­in's new he­mo­phil­ia gene ther­a­py

The EMA’s human medicines committee on Friday recommended three new drugs for approval or conditional approval, even as their US counterparts have rejected these three for various reasons.

In a major move, CHMP offered a thumbs-up to a conditional marketing authorization for the first gene therapy to treat severe hemophilia A, although the agency cautioned that it’s so far unknown how long the effects of infusion will last.

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