CAR-M era be­gins as Caris­ma dos­es first pa­tient

Last month, doc­tors at the Abram­son Can­cer Cen­ter in Philadel­phia in­sert­ed a nee­dle in­to a pa­tient with an un­treat­able tu­mor and be­gan draw­ing blood in­to a ma­chine.

The ma­chine fil­tered out every­thing but a spe­cif­ic set of im­mune cells that were then pack­aged, put on a plane and shipped, still warm, to a fa­cil­i­ty in Sun­ny­vale, CA. Over 24 days, tech­ni­cians ex­pand­ed the cells, armed them with a new kind of re­cep­tor and sent them back, now cryo­geni­cal­ly frozen, on a plane to Philadel­phia to be in­fused back in­to the pa­tient.

Saar Gill

It’s a fa­mil­iar process. A few de­tails aside, it’s played out thou­sands of times over the past half decade as pa­tients with dead­ly blood can­cers re­ceived CAR-T treat­ments, po­ten­tial­ly life-sav­ing in­fu­sions of ge­net­i­cal­ly tur­bocharged T cells. But for the first time, de­vel­op­ers used a dif­fer­ent im­mune cell, one they hope can un­lock a whole new set of pa­tients and in­cur­able tu­mors: macrophages.

Caris­ma Ther­a­peu­tics, the Uni­ver­si­ty of Penn­syl­va­nia spin­out, an­nounced to­day that they had dosed their first pa­tient with CAR-macrophages, or what they call CAR-M. Re­ly­ing on a bub­bly im­mune cell that eats pathogens and of­ten gath­ers around sol­id tu­mors, they hope it can bring the ben­e­fits of cell ther­a­py in­to places where CAR-T has con­sis­tent­ly failed.

Joshua Bauml

“CAR-T ther­a­pies have made huge ad­vances in the field of [blood can­cers], but there are ma­jor lim­i­ta­tions to uti­liz­ing the same tech­nol­o­gy in sol­id tu­mors,” Joshua Bauml, an on­col­o­gist at Penn Med­i­cine and lead in­ves­ti­ga­tor on the study, told End­points News. “And I think that this tri­al aims to over­come some of those in a very clever way.”

Biotechs and aca­d­e­m­ic re­searchers have man­aged to make CAR-Ts with re­cep­tors that go af­ter sev­er­al dif­fer­ent blood can­cers, in­clud­ing lym­phoma and mul­ti­ple myelo­ma. But ef­forts to ap­ply T cells in sol­id tu­mors have failed, in large part be­cause many such tu­mors have mech­a­nisms to keep T cells from in­fil­trat­ing their en­vi­ron­ment and de­stroy­ing can­cer cells.

Those en­vi­ron­ments, though, are of­ten swarm­ing with macrophages. That’s ac­tu­al­ly a bad thing: There are mul­ti­ple types of macrophages and tu­mors re­ly on ones that sup­press the im­mune sys­tem, ef­fec­tive­ly giv­ing the can­cer a walled-off com­pound in which to thrive.

Michael Klichin­sky

But near­ly a decade ago Uni­ver­si­ty of Penn­syl­va­nia hema­tol­o­gist Saar Gill and a grad­u­ate stu­dent, Michael Klichin­sky, fig­ured out that if you at­tached a CAR on­to a macrophage, those macrophages can en­ter the tu­mor’s en­vi­ron­ment like a Tro­jan horse. There it both di­rect­ly eats up the tu­mor and sends out sig­nals that turn bad macrophages in­to good macrophages that can kill can­cer cells and re­cruit oth­er im­mune cells to join the brigade.

Or at least it did in an­i­mal mod­els. The new tri­al is test­ing to see whether those re­sults can trans­late in­to hu­mans, be­gin­ning with 18 pa­tients who have can­cers that ex­press HER2 and have ex­haust­ed oth­er op­tions.

Caris­ma chose to start with HER2 be­cause there’s al­ready a swath of treat­ments that tar­get the re­cep­tor, CMO Deb­o­ra Bar­ton said. It helps stan­dard­ize an oth­er­wise high­ly ex­per­i­men­tal pro­ce­dure.

Deb­o­ra Bar­ton

“We don’t want to add any vari­abil­i­ty,” she told End­points.

The first group of pa­tients will re­ceive 5 bil­lion cells in 3 dif­fer­ent in­fu­sions over 5 days to en­sure noth­ing goes wrong. If that goes well, the sec­ond group will re­ceive all the cells at once. Bar­ton, though, said they have good ev­i­dence to sug­gest the ther­a­py is safe. It doesn’t re­quire the same in­tense con­di­tion­ing reg­i­men that CAR-T ther­a­pies do, and they don’t think it will trig­ger the cy­tokine re­lease syn­drome, the dan­ger­ous im­mune over-re­ac­tion that CAR-T can stim­u­late.

Bar­ton isn’t promis­ing the near-cu­ra­tive im­pact that the first CAR-T stud­ies showed. In­stead, they’re hop­ing to sim­ply show that it’s safe, that the CAR-Ms are get­ting in­to the en­vi­ron­ment around the tu­mor and that they’re hav­ing some ef­fect.

The study al­so serves as a test run for the month-long, cross-coun­try process man­u­fac­tur­ing need­ed to make the CAR-Ms. Caris­ma has checked all the lo­gis­ti­cal box­es, she said, but mak­ing a cell ther­a­py is nev­er an easy task. If it runs smooth­ly and proves safe, Caris­ma hope to move for­ward with a swath of CAR-M ther­a­pies for oth­er tu­mors and oth­er anti­gens.

“It’s a whole world of lo­gis­tics that we need to get in place, and we have it in place, but you know there are snow­storms and every­thing can hap­pen,” Bar­ton said. “Every­thing can go wrong and we’re tak­ing all mea­sures.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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David Ricks, Eli Lilly CEO (David Paul Morris/Bloomberg via Getty Images)

Eli Lil­ly set to in­vest $2.1B in home state man­u­fac­tur­ing boost

Eli Lilly is looking to expand its footprint in its home Hoosier State by making a major investment in manufacturing.

The pharma is investing $2.1 billion in two new manufacturing sites at Indiana’s LEAP Lebanon Innovation and Research District in Boone County, northwest of Lilly’s headquarters in Indianapolis.

The two new facilities will expand Lilly’s manufacturing network for active ingredients and new therapeutic modalities, including genetic medicines, according to a press release.

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US sees spike in Paxlovid us­age as Mer­ck­'s mol­nupi­ravir and As­traZeneca's Evusheld are slow­er off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

Pfiz­er and CD­MOs ramp up Paxlovid man­u­fac­tur­ing with Kala­ma­zoo plant ex­pan­sion lead­ing the way

As the Covid-19 pandemic continues to evolve, pharma companies and manufacturers are exploring how to step up production on antivirals.

Pfizer is planning to expand its Kalamazoo-area facility to increase manufacturing capabilities for the oral Covid-19 antiviral Paxlovid, according to a report from Michigan-based news site MLive. The expansion of the facility, which serves as Pfizer’s largest manufacturing location, is expected to create hundreds of “high-skilled” STEM jobs, MLive reported. No details about the project’s cost and timeline have been released, but according to MLive, Pfizer will announce the details of the expansion at some point in early June.

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FDA spells out the rules and re­stric­tions for states seek­ing to im­port drugs from Cana­da

The FDA is offering more of an explanation of the guardrails around its program that may soon allow states to import prescription drugs in some select circumstances from Canada, but only if such imports will result in significant cost reductions for consumers.

While the agency has yet to sign off on any of the 5 state plans in the works so far, and PhRMA’s suit to block the Trump-era rule allowing such imports is stalled, the new Q&A guidance spells out the various restrictions that states will have to abide by, potentially signaling that a state approval is coming.

Pfizer CEO Albert Bourla at the World Economic Forum (Gian Ehrenzeller/Keystone via AP Images)

All about ac­cess: Pfiz­er moves to a non-prof­it mod­el for drug sales in 45 low­er-in­come coun­tries

Leading the way to increase access to cheaper drugs worldwide, Pfizer said Wednesday it will provide all current and future patent-protected medicines and vaccines available in the US or EU on a not-for-profit basis to about 1.2 billion people in 45 lower-income countries.

Rwanda, Ghana, Malawi, Senegal and Uganda are the first five countries to sign on to this accord, which will also seek to blaze new paths for quick and efficient regulatory and procurement processes to reduce the usual delays in making new medicines and vaccines available in these countries.

Almirall is tapping artificial intelligence on behalf of its sales force for insights and efficiencies. (via Shutterstock)

Almi­rall rolls out sales rep ar­ti­fi­cial in­tel­li­gence sys­tem, cut­ting pre-call prep and 'wind­shield time'

Dermatology specialty pharma Almirall is making its sales reps smarter. Not with extra training or educational courses, but instead with artificial intelligence tools.

It began a soft launch of a sales rep AI and machine learning platform it calls Polaris last August in one of its 7 US coverage regions. The platform from Aktana gathers information from across Almirall internal sources and external ones – such as claims and prescribing data – to generate insights for reps. Now, instead of spending hours prepping for a sales call, Polaris can generate details about a physician’s preferences, past behaviors and prescription habits for reps in minutes, said Almirall head of commercial operations Vincent Cerio.

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Te­va, Al­ler­gan reach yet an­oth­er opi­oid set­tle­ment — ef­fec­tive­ly end­ing WV tri­al

Teva and Allergan have reached settlements with multiple states over their involvement in the opioid crisis. Their latest is worth 9 figures.

West Virginia attorney general Patrick Morrisey announced the newest settlement, worth $161.5 million, at a press conference on Wednesday. The deal would resolve claims that the companies helped fuel the state’s opioid epidemic. If it goes through, it could become the largest state-negotiated settlement in West Virginia’s history, according to Reuters.

Roche un­veils three new mon­key­pox tests as cas­es rise

Health experts maintain that the current monkeypox situation is a stark contrast to Covid. Even so, a handful of biotechs have sprung to action, including Roche, who quickly developed a set of three tests to detect the virus.

Roche and subsidiary TIB Molbiol unveiled their Lightmix Modular Virus test kits on Wednesday — three unique test kits that can help track the spread of monkeypox.

The first kit detects orthopoxviruses, including all monkeypox viruses originating from the West African and Central African forms of the virus. The second kit is a specific test that detects monkeypox viruses only, while the third simultaneously tests for both orthopoxviruses and monkeypox viruses.