Pfiz­er jumps in­to the heat­ed PhI­II race for new-wave JAK in­hibitors — but safe­ty frets loom large

Pfiz­er has racked up a pos­i­tive slate of Phase III da­ta for its an­ti-in­flam­ma­to­ry JAK1 in­hibitor abroc­i­tinib (PF-04965842), which the phar­ma gi­ant is hop­ing to steer to the FDA rel­a­tive­ly soon as it looks to get in­to a heat­ed block­buster race that’s been heav­i­ly over­shad­owed by new safe­ty warn­ings for the class.

All we’re get­ting now are some un­spec­i­fied — though promis­ing — re­sults, with the phar­ma gi­ant lay­ing claim to a sta­tis­ti­cal­ly sig­nif­i­cant re­sult against a place­bo for atopic der­mati­tis. Pfiz­er, though, wants to go up against some deeply en­trenched ri­vals in a high­ly com­pet­i­tive field, and there’s no re­al in­sight to of­fer on how that stacks up. 

Abroc­i­tinib is a JAK1 in­hibitor, look­ing to bust in­to a mar­ket dom­i­nat­ed by its own fran­chise drug Xel­janz, with Eli Lil­ly’s Olu­mi­ant an­gling in for a slice of the pie af­ter the FDA ap­proved on the low dose of the drug af­ter ini­tial­ly re­ject­ing it on safe­ty fears. 

The field was rat­tled bad­ly more re­cent­ly when Pfiz­er not­ed that the high dose of their block­buster JAK1/JAK3 in­hibitor Xel­janz was linked to a high­er rate of blood clots and death. That trig­gered reg­u­la­to­ry warn­ings on both sides of the At­lantic as they re­viewed the sit­u­a­tion. And days ago In­cyte an­nounced that it will stop co-fund­ing Olu­mi­ant as ques­tions about the cat­e­go­ry abound.

One of the many ques­tions now is whether the safe­ty is­sue at Pfiz­er will bleed over to Ab­b­Vie, which has its own JAK1, upadac­i­tinib, now un­der reg­u­la­to­ry re­view for rheuma­toid arthri­tis on both sides of the At­lantic. Gilead al­so has a lot rid­ing on fil­go­tinib, wide­ly tapped as a po­ten­tial block­buster in its own right. 

And now Pfiz­er gets to join that ma­jor league crew.

Here’s what we know:

Their drug, des­ig­nat­ed a break­through ther­a­py by the FDA, hit on the pri­ma­ry end­point for the In­ves­ti­ga­tor Glob­al As­sess­ment score of clear or al­most clear skin and a ≥2 point im­prove­ment. The drug al­so scored on the pro­por­tion of pa­tients who achieved at least a 75% or greater change from base­line in their Eczema Area and Sever­i­ty In­dex (EASI) score. “The key sec­ondary end­points were the pro­por­tion of pa­tients achiev­ing a 4 point or larg­er re­duc­tion in itch sever­i­ty mea­sured with the pru­ri­tus nu­mer­i­cal rat­ing scale and the mag­ni­tude of de­crease in the pru­ri­tus and Symp­toms As­sess­ment for Atopic Der­mati­tis.”

Dis­con­tin­u­a­tion rates for the two dos­es test­ed were low­er than in the place­bo arm, but no de­tails on ad­verse events were re­port­ed.

More Phase III re­sults will be avail­able lat­er in the year.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Eli Lil­ly's an­ti­body cuts risk of Covid-19 by up to 80% among the most vul­ner­a­ble — but will it have a place next to vac­cines?

Eli Lilly says bamlanivimab lowered the risk of contracting symptomatic Covid-19 in a first-of-its-kind trial involving nursing home residents and staff, paving the way for a new option to protect against the virus.

But how big of an impact it might have, and what role it will play, at a time vaccines are being rolled out to the exact population it is targeting still remains unclear.

Among 965 participants in the study — all of whom tested negative for the coronavirus at baseline — the number of symptomatic cases reported in the bamlanivimab arm was 57% lower than that in the placebo arm (odds ratio 0.43, p=0.00021). In addition to that primary endpoint, all secondary endpoints reached statistical significance.

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Janet Woodcock (AP Images)

End­points poll: Janet Wood­cock takes the (in­ter­im) helm at the FDA. And a large ma­jor­i­ty of our read­ers want her to stay there

It’s official: Janet Woodcock is now the acting chief of the FDA.

And — according to an Endpoints poll — most industry readers would like her to stay there, although a significant minority is strongly opposed.

To recap: Joe Biden is reportedly choosing between Woodcock and former deputy FDA commissioner Joshua Sharfstein as his nominee for the permanent position. Given their respective track records, the decision is set to determine the agency’s lodestar for years to come.

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What’s next for End­points — and how to sup­port our in­de­pen­dent bio­phar­ma news mis­sion

The firehose of biopharma news is gushing these days.

That’s why broader and deeper is the theme for 2021 at Endpoints. You can expect new coverage outside our core R&D focus, with deeper reporting in some key areas. When John Carroll and I launched Endpoints nearly five years ago, we were wading in waist-high waters. Now we’re a team of 25 full-time staffers (and growing) with plans to cover the flood of biopharma news, Endpoints-style.

Charlie Fuchs, Roche and Genentech global head of product development for oncology and hematology (Yale Cancer Center)

Yale can­cer spe­cial­ist Char­lie Fuchs tapped as new glob­al de­vel­op­ment chief for Roche/Genen­tech

Roche and their big sub Genentech have just recruited a top cancer specialist at Yale to head up global product development in oncology and hematology.

I just got word that the pharma giant, which leads one of the most active cancer research operations in the world, recruited Charlie Fuchs, director of the Yale Cancer Center and physician-in-chief of Smilow Cancer Hospital. He’ll join the global operation March 1 and will be based in South San Francisco, where Genentech is based.

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Jonathan Weissman (MIT)

Can a new CRISPR tech­nique un­lock the se­crets of how can­cer spreads?

Jonathan Weissman’s team watched the cancer cells spread across the doomed mouse. Engineered with a bioluminescent enzyme, they appeared in scans first as a small navy blue diamond lodged near the heart; a week later, as a triangle splayed across the mouse’s upper body, with streaks of green and two distinct bright red hubs of activity. By day 54, the mouse resembled a lava lamp.

The images would have been familiar to any cancer biologist, but they didn’t actually tell you much about what was going on: why the cancer was metastasizing or which cells were responsible. For that, Weissman’s team had designed a new tool. Inside the original navy blue diamond, they had engineered the microbiological equivalent of an airplane’s black box — a “molecular recorder” that, after the mouse’s death, could allow them to extract the cells and wind back intimate footage of a single cancer’s ascent.

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Glax­o­SmithK­line scraps a LAG3 study, mark­ing an­oth­er fail­ure for the pipeline af­ter a crit­i­cal set­back

Another gap has appeared in GlaxoSmithKline’s pipeline.

Friday morning the Australian biotech Immutep put out word that Hal Barron’s R&D group at GSK had decided to scrap a Phase II proof-of-concept study in ulcerative colitis for their anti-LAG3 therapy GSK2831781. According to the biotech, the program didn’t survive an interim review.

The trial was stopped by GSK based on the assessment of clinical data as part of a planned interim analysis conducted in consultation with the trial’s Data Review Committee. GSK is conducting further reporting, assessment and analyses of the efficacy and safety data and evaluating the biology to determine next steps for the GSK2831781 development program.

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Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.