New safe­ty da­ta ex­pose po­ten­tial weak­ness as Pfiz­er's abroc­i­tinib takes on Dupix­ent in eczema

Last Sep­tem­ber, when Pfiz­er cel­e­brat­ed pos­i­tive da­ta from a sec­ond Phase III study of abroc­i­tinib, many watch­ers ap­plaud­ed the ef­fi­ca­cy but were still wait­ing to see whether the JAK1 in­hibitor is “safe enough to be a for­mi­da­ble com­peti­tor to Dupix­ent,” the clear leader in the atopic der­mati­tis field. The full slate of safe­ty da­ta are now out and, ac­cord­ing to one an­a­lyst, the an­swer is: prob­a­bly not.

The broad­er class of JAK in­hibitors has been plagued by se­ri­ous side ef­fects re­lat­ing to blood that threat­en to lim­it their adop­tion, and JAK1 drugs — which tar­get a more spe­cif­ic sub­type of the ki­nase — are still un­der heavy scruti­ny.

In a note, Jef­feries’ Re­gen­eron bull Biren Amin sin­gled out re­duc­tions in platelet count in JADE MONO-2 as a par­tic­u­lar cause for con­cern.

At week 4, platelet re­duc­tions of 26% were not­ed for the 200mg dose, 19% in the 100mg group, and less than 1% for those on place­bo. In the drug’s de­fense, the re­searchers wrote that platelet counts “re­turned to­wards base­line val­ues there­after de­spite con­tin­u­a­tion of treat­ment,” and that there were no re­ports of bleed­ing dis­or­ders in any treat­ment group.

Still, the fact that the mech­a­nism lead­ing to platelet re­duc­tions is un­known could be a con­cern, Amin not­ed.

Then there’s the da­ta point that 1.9% of pa­tients in the 100mg group re­port­ed a se­ri­ous in­fec­tion, com­pared to none on 200mg and 1.3% on place­bo. Her­pes zoster was ob­served in 2 pa­tients tak­ing 200mg (1.3%).

In Ab­b­Vie’s case, Amin point­ed out, 1% of pa­tients re­port­ing se­ri­ous in­fec­tions, op­por­tunis­tic in­fec­tions and her­pes zoster was enough for reg­u­la­tors to slap a black box warn­ing on Rin­voq’s rheuma­toid arthri­tis la­bel.

“Tak­en to­geth­er, giv­en the safe­ty sig­nals around con­cerns for JAK1i class, ini­tial adop­tion of abroc­i­tinib might be lim­it­ed to se­vere pa­tients or on­ly be used as a short course of in­duc­tion be­fore switch­ing pa­tients to oth­er ther­a­pies to re­duce the ex­po­sure,” he wrote.

For now, Pfiz­er is fo­cus­ing on the bright side, em­pha­siz­ing how abroc­i­tinib can of­fer po­ten­tial symp­tom re­lief to pa­tients — in­clud­ing the both­er­some itch that comes with mod­er­ate to se­vere atopic der­mati­tis. The rate of ad­verse events over­all was al­so low in the tri­al, back­ing the claim that the drug was well-tol­er­at­ed. Abroc­i­tinib is al­so giv­en in pill form rather than sub­cu­ta­neous­ly, of­fer­ing pa­tients a more con­ve­nient choice.

But as Sanofi and Re­gen­eron con­tin­ue to groom Dupix­ent — the prize gem of a fore­gone re­la­tion­ship that gen­er­at­ed $2.32 bil­lion in 2019 rev­enue — in­to an even big­ger block­buster, the fight is on­ly be­gin­ning to play out.

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Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

Roche gains rights to co-develop and co-commercialize the drug, with sole marketing responsibility for places outside the US and China (where CStone has staked its claim).

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President Trump (left) and NIAID chief Anthony Fauci in the White House press room, April 22, 2020 (Michael Reynolds/Sipa via AP Images)

White House tries to dis­cred­it An­tho­ny Fau­ci — could he be on his way out?

For two months in late winter and early spring, Anthony Fauci and President Trump stood in uneasy co-existence at White House briefings — an unlikely truce between an infectious disease official who had helped combat AIDS and Ebola and a president who repeatedly denied the danger of a virus that would go on to kill 100,000 Americans, repeatedly rejected masks and certain social distancing efforts, and promoted a drug with little scientific basis.

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Stéphane Bancel, Moderna CEO (Andrew Harnik/AP Images)

A top an­a­lyst turns the spot­light on Mod­er­na, fu­el­ing a fast-and-fu­ri­ous Street race over the fu­ture of mR­NA

Bioregnum Opinion Column by John Carroll

Four months ago, one of the favorite talking points on the biopharma social media wave length was whether Moderna shares $MRNA were priced right or were wildly inflated.

After all, said the naysayers, the company had never actually pushed a treatment to an approval. Did messenger RNA really work, coding cells to make a drug or a vaccine? And how about all that chatter about how ‘secretive’ they are, or were?

Now, as CEO Stéphane Bancel and the top execs push the company to the forefront of a frantic race to develop the first vaccine to fight against the reignited wildfire spread of Covid-19, all those questions have been magnified — along with the stock price.

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Andrew Allen, Gritstone Oncology CEO

A neoanti­gen pi­o­neer says its tech is work­ing great. So what wrecked the share price?

Gritstone Oncology was one of the original neoantigen upstarts, raising cash and planning to disrupt the immuno-oncology field with a bold new approach to fighting cancer with a new brand of vaccines.

On Monday, the crew in charge ran out a full display of what they’ve been seeing in a Phase I study. And everything seems to be working perfectly with one big exception: It didn’t significantly shrink tumors, let alone eradicate them.

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Janet Woodcock, CDER chief (AP Images)

More Warp Speed con­tracts com­ing, vac­cine pro­duc­tion to be­gin in 4-6 weeks — of­fi­cials

Operation Warp Speed has already handed out 4 of what they once said would be 3-5 major contracts to develop Covid-19 vaccines, but administration officials indicated Monday that more would be on their way.

“The slate is not closed,”  a senior HHS official said on a call with reporters. “We’ve invested in four … but the slate is not closed.”

At the same time, the official indicated that Warp Speed would continue to focus on three technologies: mRNA, viral vectors and protein subunits. That leaves the door open for a wide range of platforms, notably including both of Merck’s vaccine candidates — one of which has already received BARDA funding — and one of Sanofi’s candidates. It appears to preclude, though, the potential for Inovio and Vaxart, among certain other small developers that have hyped their ties to the Trump administration, to be included.

En­gi­neer­ing an on/off switch for CAR-T out of yeast and Juras­sic Park

Almost as soon as CAR-T emerged in the mid-2010s as a near-cure for some cancers, so did a question: How do you give this without risking killing patients?

At the time, James Patterson was wrapping an MD-PhD at a yeast lab at London’s Francis Crick Institute. Yeast may seem an unlikely place to find a fix for cancer therapy, but reading through other researchers’ solutions to CAR-T’s toxicity, Patterson wondered if a method long used by yeast biologists called auxotrophy might be useful. You genetically modify cells to make them dependent on a particular nutrient. Then you can make them live or die — proliferate or deplete — by giving or taking away that nutrient.

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Stéphane Bancel, Moderna CEO (Andrew Harnik/AP Images)

Covid-19 roundup: Af­ter re­ports of de­lays, gov­ern­ment dis­putes, Mod­er­na sets PhI­II launch; Clin­i­cal tri­als have re­turned — for now

After reported disputes between company officials and government scientists delayed a much-anticipated Phase III trial, Moderna has set a start date for the 30,000-person study that will determine whether its vaccine can actually protect people from developing Covid-19.

The study will start on July 27th, according to clinicaltrials.gov, in line with Moderna’s promise of a July launch but a bit more than 2 weeks after the July 10 date Reuters reported the trial was originally supposed to start. Conducted in collaboration with the NIH and BARDA, the trial will inoculate volunteers with placebo or mRNA-1273 at 87 sites across the country.

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Albert Bourla, AP

Covid-19 roundup: CanSi­no eyes more over­seas PhI­II sites as Cana­da tri­al re­port­ed­ly stalls; In­di­an drug­mak­er surges on 30-per­son da­ta

Having leveraged connections in Canada for a planned Phase III trial of its Covid-19 vaccine, CanSino is venturing out to a few more others as it plots a global late-stage program.

“We are contacting Russia, Brazil, Chile and Saudi Arabia, and it’s still in discussion,” Dongxu Qiu, executive director and co-founder of CanSino, said at a conference in Suzhou, China, per Reuters.

The trial is likely to start “pretty soon,” he added, with plans to recruit 40,000 participants total.

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