Juno scram­bles to avoid be­ing crushed by a hold, but ex­perts ques­tion its best case sce­nario

“Flu­dara­bine in some ways acts like a dose am­pli­fi­er,” says Juno CEO Hans Bish­op, ex­plain­ing the com­pa­ny’s the­o­ry of what went wrong.

John Car­roll, Ed­i­tor

About the last thing a biotech wants to see in the lead­up to a wide­ly her­ald­ed reg­u­la­to­ry fil­ing is a clin­i­cal hold from the FDA af­ter pa­tients in a piv­otal tri­al are killed by your treat­ment. The in­stinc­tive re­sponse is to get out in front of the dis­as­ter, see if you can iden­ti­fy a fac­tor oth­er than your drug that could have caused the deaths, and re­as­sure in­vestors that you have a plan – or soon will have one – that will get you back on track AS­AP.

Then, with­out burn­ing through too many hours be­tween the hold and the news, you host a press con­fer­ence and put out a re­lease and hope your stock doesn’t get evis­cer­at­ed in the re­ac­tion.

By that mea­sure, the past 24 hours at Juno Ther­a­peu­tics must have been a blur of non­stop ac­tion. They not on­ly im­me­di­ate­ly iden­ti­fied the cause of death in their lead CAR-T study, cere­bral ede­ma, they al­so ID’d a prime sus­pect, new­ly added flu­dara­bine, which in­ves­ti­ga­tors were us­ing to help prep pa­tients for a bet­ter re­sponse to the treat­ment.

So­lu­tion: Drop the flu­dara­bine, get the doc­u­men­ta­tion back to the FDA and wait for the green light. All while as­sur­ing in­vestors that this could all be over soon.

But it may not be any­thing near­ly as easy as that at Juno. And there are ma­jor im­pli­ca­tions here for the whole field.

Sal­ly Church, a No­var­tis vet with a doc­tor­ate from King’s Col­lege, writes the high­ly re­gard­ed Biotech Strat­e­gy Blog, where she spe­cial­izes in cov­er­ing can­cer treat­ments. She’s been fol­low­ing the CAR-T field close­ly for 4 years, and she was im­me­di­ate­ly puz­zled by Juno’s po­si­tion.

Sal­ly Church, Biotech Strat­e­gy Blog

The chemo flu­dara­bine was used in the study to com­plete a round of lym­phode­ple­tion, elim­i­nat­ing dis­eased B cells to as­sist the new­ly in­sert­ed CAR-T cells to re­pop­u­late and do their work. It’s the same type of con­di­tion­ing pa­tients re­ceive for hematopoeitic stem cell trans­plants. It’s al­so a pro­ce­dure used in oth­er CAR-T tri­als, with no his­to­ry of cere­bral ede­mas. And there’s no record of flu­dara­bine be­ing linked to cere­bral ede­mas, she writes in her blog. Church gave me ac­cess to the ar­ti­cle, which you can find here. (Note: There is a pay wall. If you’ve got the bud­get, we high­ly rec­om­mend you sign up.)

Then she asked a group of hema­tol­o­gists what they knew of a con­nec­tion. Re­sponse: Noth­ing. And she queried Dr. Stephan Grupp (CHOP), who “prob­a­bly treat­ed more pe­di­atric ALL pa­tients with CAR T cell ther­a­py than any­one”:

“We have not seen sig­nif­i­cant cere­bral ede­ma in any of our pe­di­atric ALL pa­tients on the CHOP/Penn study treat­ed with CTL019, many of whom re­ceived flu­dara­bine. CNS-re­lat­ed side ef­fects have been seen, in­clud­ing con­fu­sion, apha­sia and seizures in a small num­ber of pa­tients, but these ef­fects have all re­solved. Ob­vi­ous­ly, it is al­ways hard to at­tribute tox­i­c­i­ty to the chemo vs. the CAR T cells when both are giv­en around the same time, but we be­lieve the self-lim­it­ed CNS side ef­fects we have re­port­ed are more like­ly to be due to the T cells.”

Both Juno as well as ri­val Kite Phar­ma use CD-28 as a co-stim­u­la­tion do­main, she adds. Penn/CHOP/No­var­tis use 4–1BB. There are dif­fer­ences in pa­tient re­spons­es, but no cas­es of cere­bral ede­ma have been re­port­ed by Kite so far, though Kite has had the same lim­it­ed CNS is­sues that Juno has re­port­ed.

It’s not un­usu­al to see a dif­fer­ence of opin­ion among sci­en­tists and com­pa­nies en­gaged in ri­val stud­ies. The point here is that there’s thought­ful con­sid­er­a­tion of a much big­ger mys­tery about what went wrong for Juno. And a mys­tery is ex­act­ly what Juno doesn’t want to ex­plore – es­pe­cial­ly when your com­pe­ti­tion at Kite an­nounced that it had ful­ly en­rolled its ri­val study on the same day Juno stunned in­vestors with news of the clin­i­cal hold.

Fur­ther con­found­ing all of this, Bish­op re­port­ed a few days ago that he had sold $4.5 mil­lion in stock; a small part of his hold­ings, but not the kind of thing in­vestors like to see when bad news fol­lows soon af­ter.

Juno has al­ready ac­knowl­edged that its pre­dic­tion of a 2017 mar­ket launch will have to be de­layed a year. And for now, de­spite its con­fi­dent as­ser­tion that this can all be re­solved in short or­der, there’s rea­son to be­lieve that this could go on for much longer than Juno wants.

— John Car­roll@John­Cendpts

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.

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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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.

Greg Mayes, Antios Therapeutics CEO

An­tios' HBV col­lab axed af­ter clin­i­cal hold, but biotech be­lieves safe­ty in­ci­dent is not treat­ment-re­lat­ed

The FDA has placed a clinical hold on a Phase IIa study of Antios Therapeutics’ investigational hepatitis B med, CEO Greg Mayes confirmed to Endpoints News in an emailed statement.

A safety report was delivered to the biotech on May 17 after a patient dosed in a triple combination cohort of the study had experienced bradycardia and hypotension. The triple combo included Antios’ ATI-2173, Assembly Biosciences’ vebicorvir and Viread, an approved antiviral for HIV and hepatitis B.

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Tim Schoen, BioMed Realty CEO

Life sci­ences de­vel­op­er Bio­Med Re­al­ty buys San Fran­cis­co ho­tel for $75M — re­port

In a somewhat unconventional deal, life sciences real estate developer BioMed Realty has bought a 169-room Hilton Garden Inn in South San Francisco for $75 million, the San Francisco Business Times reported.

BioMed Realty, an affiliate of Blackstone, has multiple life sciences and technology office projects in the Bay Area, including three sites within a five-minute drive of the hotel.

While the sale of the hotel property was announced earlier this month, the sellers, Summit and GIC, did not identify the buyer at the time.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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