#ASH17: The big los­er in CAR-T, Juno is mak­ing a bid to seize the fast lane to fron­trun­ner sta­tus

Juno Ther­a­peu­tics $JUNO may be play­ing catchup in CAR-T. But if the lat­est cut of its 3-month DL­B­CL da­ta at the top dose holds up, the biotech won’t be play­ing for sec­ond — or third — place.

In their ab­stract out for ASH this morn­ing, Juno ex­ecs spelled out a key piece of da­ta for the high dose arm of the ear­ly study on JCAR017. Ze­ro­ing in on that one snap­shot, re­searchers say they tracked an 80% over­all re­sponse rate and a 73% com­plete re­sponse rate at 3 months for the high dose among a “piv­otal core” group of 15 pa­tients.

Gilead’s Kite and No­var­tis saw a slight de­cline in the CR rates to the low 30s go­ing from 3 to 6 months, leav­ing Juno a win­dow for con­sid­er­able im­prove­ment.

To be sure, Juno still has a long way to go af­ter its lead JCAR015 proved to be a lethal, tox­ic dis­as­ter in what was in­tend­ed to be a piv­otal study. But the biotech isn’t at all con­tent to be re­main­dered to the sec­tion of the in­dus­try that counts the num­ber of pa­tients killed in a failed study. In­stead, Juno be­lieves that its fol­low-up pro­gram will prove that the big sums gam­bled on its tech­nol­o­gy will show that they came up with a bet­ter CAR-T, with a more ef­fec­tive man­u­fac­tur­ing process and a safer pro­file that will ul­ti­mate­ly carve out a big place for it­self in the mar­ket.

In­vestors liked what they were see­ing, dri­ving up Juno’s shares by 10% this morn­ing.

Sunil Agar­w­al

Every­thing is rid­ing on this one. There won’t be much chance for a third shot at suc­cess.

What’s dif­fer­ent this time?

“The anal­o­gy I’ll give you,” says R&D chief Sunil Agar­w­al: “Small changes in the an­ti­body world can make big dif­fer­ences; all CARs are not the same.”

There’s more to come at ASH, he adds, where they can re­view the re­sponse for a big­ger group of pa­tients. But the es­sen­tial ef­fi­ca­cy and safe­ty pro­file on dis­play to­day, he adds, isn’t go­ing to change.

Says Agar­w­al: “I think these da­ta con­tin­ue to sup­port a best-in-class pro­file.”

For one, there’s the switch to the 4-1BB cos­tim­u­la­to­ry do­main, which al­lows for a slow and steady ac­ti­va­tion that sets the foun­da­tion for a more durable re­sponse.

Hans Bish­op

But that’s a fea­ture that No­var­tis’ CAR-T shares as well. Juno CEO Hans Bish­op tells me the “pre­cise pro­duc­tion” val­ues used now in mak­ing the ther­a­py from cells ex­tract­ed from pa­tients is just far more pre­cise.

“We know CD4 and CD8 cells act dif­fer­ent, CD8 cells are more po­tent,” says Bish­op. Get­ting the right mix with a mea­sured ex­pan­sion of cells now is part of a pre­cise­ly arranged pro­duc­tion recipe that dis­tin­guish­es JCAR017 from the rest, he as­serts.

Bish­op isn’t talk­ing ex­act pric­ing yet, and won’t un­til much lat­er in the game. But he does want peo­ple to un­der­stand that to be com­pet­i­tive here in­volves beat­ing out some steep ex­ist­ing costs in treat­ing DL­B­CL or ALL. Safe­ty, he says, will play a big role in that.

The lat­est up­date on the da­ta re­mains with 1 pa­tient suf­fer­ing from cy­tokine re­lease syn­drome, and 14% with neu­ro­tox­i­c­i­ty run­ning from Grade 1 to Grade 4. That’s not a per­fect score, by any means, but in this world Bish­op feels the num­bers give Juno an ad­van­tage over worse is­sues with the mar­ket lead­ers.

Close to two thirds of the pa­tients in their study nev­er ex­hib­it­ed any signs of tox­i­c­i­ty, ei­ther cy­tokine re­lease syn­drome or neu­ro­tox­i­c­i­ty, which ul­ti­mate­ly de­stroyed Juno’s lead ther­a­py, JCAR015, af­ter it killed 5 pa­tients. In this world, any tox, Grade 1 or above, earns pa­tients a one-way trip to the hos­pi­tal, which doesn’t come cheap. By avoid­ing tox, Juno hopes to prove that most pa­tients can be treat­ed in an out­pa­tient set­ting, vast­ly re­duc­ing their over­all cost — which some ex­perts say may well range from $1 mil­lion to $1.5 mil­lion, all in.

It’s a com­pelling ar­gu­ment, and one that Juno has care­ful­ly craft­ed af­ter one of the worst clin­i­cal set­backs in re­cent his­to­ry. Their R&D work here will be care­ful­ly scru­ti­nized at every step. To get on to the mar­ket, they’ll have to pass muster at the hands of a group of reg­u­la­tors em­bar­rassed by their abrupt and in­ex­plic­a­ble de­ci­sion to lift the orig­i­nal hold on JCAR015 af­ter just a few days — al­low­ing more pa­tients to die.

Juno has a high bar to clear, but they’re tak­ing a run­ning leap at it.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

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Vir's CMO says he's sur­prised that a low dose of their he­pati­tis B drug ap­pears promis­ing in ear­ly slice of da­ta — shares soar

Initial topline data from a Phase I study of a new therapeutic for chronic hepatitis B virus was so promising that it surprised even the CMO of the company that produces it.

Vir Biotechnology on Tuesday announced that its VIR-3434 molecule reduced the level of virus surface antigens present in a blinded patient cohort after eight days of the trial with just a single 6 mg dose. Six of the eight patients in the cohort were given the molecule, and the other two a placebo—all six who received the molecule saw a mean antigen reduction of 1.3 log10 IU/mL, Vir said.

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David Marek, Myovant

My­ovant beefs up da­ta pack­age in NDA #3, boost­ing its case for longterm dos­ing of Pfiz­er-part­nered re­l­u­golix

When Pfizer handed over $650 million in cash to partner on Myovant’s relugolix, the pharma giant made clear that the deal — valued at $4.2 billion total — was just as much about the approved indication of prostate cancer as the two women’s health conditions the drug could treat.

A month later, the two companies are offering another glimpse of the therapy’s longterm potential in endometriosis.

Look­ing to win over some skep­ti­cal an­a­lysts, Rhythm beats the drum on in­ter­im da­ta in PhII bas­ket study for ad­di­tion­al in­di­ca­tions

Rhythm Pharmaceuticals has been working toward expanding the FDA approval they received just two months ago for three rare genetic disorders that result in obesity. In December, their Phase III cut of data saw mixed reactions from analysts, but new interim results released Tuesday may provide more excitement.

In an ongoing Phase II study for setmelanotide across individuals with one of three distinct rare genetic diseases of obesity, 65 patients had reached the Dec. 17 cutoff date for evaluation. Among patients who met the primary endpoint of at least 5% weight loss over three months, Rhythm saw an average reduction of no less than 7.1% in any of the groups.

Eli Lil­ly demon­strates that 2 an­ti­bod­ies beat 1 for guard­ing against se­vere Covid-19. But can that solve the first an­ti­body’s prob­lem amid slow up­take?

It seems safe to say that two antibodies are better than one.

Eli Lilly released the largest results yet on Tuesday for their Covid-19 neutralizing antibody cocktail, announcing that the combo reduced deaths and hospitalizations in coronavirus patients by 70%. Across 1,000 patients, there were 11 such events in the treatment group and 36 in the placebo group.

The breakdown for deaths alone was even starker: 10 in the placebo group and 0 in the treatment group. Lilly added that the drug hit secondary endpoints for reducing viral load and alleviating symptoms, although they did not disclose numbers.

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