EMA im­pos­es for­mal lim­it on Xel­janz pre­scrip­tion as reg­u­la­tors con­tin­ue to re­view safe­ty con­cerns

Three months af­ter Pfiz­er flagged blood clot is­sues and a high­er rate of deaths for rheuma­toid arthri­tis pa­tients tak­ing the 10 mg dose of Xel­janz (to­fac­i­tinib) in a post-mar­ket­ing safe­ty study, the EMA has hand­ed down of­fi­cial re­stric­tions in its use.

The agency’s safe­ty com­mit­tee — phar­ma­covig­i­lance risk as­sess­ment com­mit­tee, or PRAC — is still in the process of re­view­ing the ev­i­dence, but it is alarmed enough to ban pre­scrip­tion of the 10 mg twice dai­ly reg­i­men in any pa­tients with a high risk of blood clots in the lungs. Those who have heart fail­ure, can­cer, a his­to­ry or pre­dis­po­si­tion to blood clots are on the list, as are pa­tients tak­ing hor­mone-based ther­a­pies or prepar­ing/re­cov­er­ing from ma­jor surgery.

And reg­u­la­tors made sure to be crys­tal clear about the im­pli­ca­tions:

The new ad­vice means that, since 10 mg is the on­ly rec­om­mend­ed start­ing dose for ul­cer­a­tive col­i­tis, pa­tients with this con­di­tion who are at high risk of blood clots must not be start­ed on Xel­janz. Pa­tients at high risk cur­rent­ly tak­ing this dose for any con­di­tion must be switched to al­ter­na­tive treat­ments.

The for­mal — though tem­po­rary — re­stric­tions fol­low an ear­li­er warn­ing, which di­rect­ed health­care pro­fes­sion­als to mon­i­tor pa­tients for signs and symp­toms of blood clots in the lungs. Doc­tors were al­so ad­vised to stick to the rec­om­mend­ed 5 mg dose when treat­ing rheuma­toid arthri­tis.

In Feb­ru­ary, Pfiz­er yanked the 10 mg dose from the on­go­ing A3921133 study in rheuma­toid arthri­tis, switch­ing pa­tients to the 5 mg dose af­ter doc­u­ment­ing “a sta­tis­ti­cal­ly and clin­i­cal­ly im­por­tant dif­fer­ence in the oc­cur­rence of pul­monary em­bolism” as well as an im­bal­ance in the rate of death. In ad­di­tion to the 5 mg arm, there was al­so a con­trol group tak­ing a TNF in­hibitor.

The FDA sound­ed its own alarm days lat­er, launch­ing an in­ves­ti­ga­tion and urg­ing pa­tients to seek med­ical care if they ex­pe­ri­ence a blood clot in the lung, chest pains, or start cough­ing up blood.

Xel­janz was the orig­i­nal JAK in­hibitor to hit the mar­ket, rack­ing up block­buster sales in the sev­en years it’s been ap­proved by the FDA (the EMA nod came much lat­er in 2017). But safe­ty is­sues have cloud­ed both the drug and the en­tire class, as man­i­fest­ed by the FDA’s de­ci­sion to slap down a high­er, 4 mg dose of Eli Lil­ly’s Olu­mi­ant (baric­i­tinib) and al­low on­ly the 2 mg dose in the mar­ket.

None of that has stopped Pfiz­er from step­ping up its JAK game, though. Just this week, the phar­ma gi­ant tout­ed a pos­i­tive slate of Phase III da­ta for its JAK1 in­hibitor abroc­i­tinib (PF-​04965842) in atopic der­mati­tis, look­ing to get in­to a heat­ed block­buster race.

Ab­b­Vie’s own JAK1, upadac­i­tinib, is now un­der reg­u­la­to­ry re­view for rheuma­toid arthri­tis on both sides of the At­lantic. Gilead put its bet on fil­go­tinib, wide­ly tapped as a po­ten­tial block­buster in its own right. Both com­pa­nies are giv­ing them­selves high marks on safe­ty, sig­nal­ing a fierce mar­ket­ing ri­val­ry to come.


Im­age Source: Pfiz­er

Bio­mark­er 'roadmap­s' and the fu­ture of can­cer R&D; Cur­tain rais­es on #AS­CO22; Pfiz­er, No­var­tis tack­le drug ac­cess; 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.

While this was not a week for earth-shattering news, there were certainly a lot of interesting tidbits. If you found this recap helpful, please recommend it to your friends and colleagues. We’ll see you on the other side of the long weekend.

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Keep­ing pres­sure on Am­gen, Mi­rati draws mixed re­views on lat­est cut of KRAS da­ta

As the close runner-up to Amgen’s Lumakras in the KRAS race, any data cut from Mirati’s adagrasib continues to draw scrutiny from analysts. And the latest batch of numbers from ASCO is a decidedly mixed bag.

While a quick comparison suggests that adagrasib spurred slightly more responses and led to a longer overall survival than Lumakras among a group of non-small cell lung cancer patients, its duration of response appears shorter and the safety profile continues to spark concern.

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Ann is one of ViiV Healthcare's newest spokespeople as the retired school administrator speaks up about her HIV status.

GSK's Vi­iV de­buts next evo­lu­tion in HIV med Dova­to cam­paign with new spokes­peo­ple and new mes­sage

When Ann saw the first TV commercials for HIV medicine Dovato, she didn’t see herself represented. So the 74-year-old retired school administrator who’s been living with HIV since 1998, reached out to GSK’s ViiV Healthcare and asked why not?

Now Ann is one of three people starring in ViiV’s latest Dovato campaign called “Detect This.” The next-step evolution in the branded campaign plays on the word “detect” — often used in describing HIV status under control as undetectable — but in this case, uses the word as a directive for people to understand they can use fewer medicines.

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Switzer­land to de­stroy over 600,000 ex­pired dos­es of Mod­er­na Covid vac­cine

As concerns related to uptake and distribution continue to linger, Switzerland is among the first countries that plans to destroy hundreds of thousands of expired and unused Covid-19 vaccine doses.

The European country said it plans to destroy more than 600,000 doses of Moderna’s Spikevax Covid-19 vaccine as the doses have reached their expiration date.

However, Moderna CEO Stéphane Bancel told the World Economic Forum in Davos, Switzerland that he’s in the process of throwing 30 million doses in the garbage, exclaiming, “We have a big demand problem.”

Lina Khan, FTC chair (Graeme Jennings/Pool via AP Images)

Pile-on over PBMs con­tin­ues with FTC com­ments and a new bi­par­ti­san Sen­ate bill

More than 500 stakeholders sent comments to the FTC on whether the commission should look further into pharma middlemen, known as PBMs, with many of the commenters calling for more federal oversight.

Similar to the critical open comment period in a deadlocked FTC session last February, pharmacies and pharmacy groups are continuing to call out the lack of transparency among the top 3 PBMs, which control about 80% of the market.

Pharma brands are losing their shine with US consumers who are now thinking about the economy and inflation instead of Covid. (Credit: Shutterstock)

Phar­ma brands fade in an­nu­al Har­ris con­sumer vis­i­bil­i­ty poll: Mod­er­na drops off and Pfiz­er dips

As Covid-19 concerns are fading in the US, so is biopharma visibility. The annual Axios Harris Poll survey to determine and rank the 100 most top-of-mind brands in the US finds Moderna, which was No. 3 last year, not on the list at all for 2022, and Pfizer sinking 37 spots.

However, it’s not that Moderna or Pfizer did anything wrong, it’s just that Americans have moved on to other worries beyond Covid.

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HHS Secretary Xavier Becerra (Jacquelyn Martin/AP Images)

HHS fin­ish­es off Trump-era rule that would've erased ba­sic FDA regs with­out fre­quent re­views

HHS on Thursday finalized its decision to withdraw a rule, proposed just before former President Donald Trump left office, that would’ve caused thousands of HHS and FDA regulations to automatically expire if they weren’t reviewed within two years, and every 10 years thereafter.

The decision follows the filing of a lawsuit last March, in which several nonprofits alleged that the outgoing administration planted “a ticking timebomb” for HHS, essentially forcing it to devote an enormous amount of resources to the unprecedented and infeasible task of reviewing thousands of regulations regularly.

Tran­si­tion to new Eu­ro­pean clin­i­cal tri­als in­fo sys­tem starts slow­ly

At the end of January, the European Medicines Agency officially launched its new clinical trials info system (CTIS), although the migration to the new platform has only really just begun, and sponsors have until the end of January 2023 before all initial trial applications must be submitted through CTIS.

Overall, 56 clinical trial applications have been submitted in CTIS during the first 3 months since the launch of the system on Jan. 31, according to new data posted by the EMA. By comparison, about 4,000 new trials are authorized each year across Europe.

Vi­iV Health­care looks to make long-act­ing HIV pre­ven­tion shot ac­ces­si­ble in low- and mid­dle-in­come coun­tries

The Joint United Nations Programme on HIV and AIDS set a lofty goal back in 2019 to end the HIV epidemic by 2030. But according to the World Health Organization, infection rates are not falling rapidly enough to meet that target.

GSK’s ViiV Healthcare thinks it can help change that.

On Friday, ViiV announced that it’s in talks with the UN-backed Medicines Patent Pool (MPP) for patent rights to its cabotegravir long-acting HIV injectable for pre-exposure prophylaxis (PrEP) in low- and middle-income countries.