Stung by pa­tient deaths, a small Juno study points to a Goldilocks for­mu­la for CAR-T

For Juno, the hunt to find just the right mix­ture of T cells along with an ef­fec­tive reg­i­men to prep pa­tients for their CAR-T ther­a­py has had a lethal his­to­ry, tan­gling up de­vel­op­ment time­lines in a way that has ced­ed the lead in the field to ri­val Kite.

Stan­ley Rid­dell

But in a new, small study in­volv­ing one of their most ad­vanced CAR-Ts, an in­ves­tiga­tive team feels that they came up with just the right recipe. And that could have big im­pli­ca­tions for an­oth­er CAR-T pro­gram in which Juno holds high hopes for a come­back.

The drug in­volved in the study is called JCAR014, and the in­ves­ti­ga­tors say that they came up with a one-on-one mix of CD4+ helper cells with CD8+ killer cells that showed a re­mark­able abil­i­ty to wipe out can­cer cells that ex­press CD19, which has been the big ini­tial tar­get for all the play­ers in the van­guard of CAR-T work.

Sig­nif­i­cant­ly, the in­ves­ti­ga­tors al­so con­clud­ed that adding flu­dara­bine to cy­clophos­phamide (Cy/Flu) in a cock­tail to prep pa­tients cre­ates the right en­vi­ron­ment for the T cells to grow in the body. Half of the 18 pa­tients with non-Hodgkin lym­phoma who got the Cy/Flu com­bo had a com­plete re­sponse to the ther­a­py, com­pared to on­ly 8% of the group who re­ceived on­ly cy­clophos­phamide.

The team point­ed out that these re­sults could in­di­cate sim­i­lar out­comes for JCAR017, which is now in ear­ly stud­ies. Juno has tapped JCAR017 as a po­ten­tial “best-in-class” treat­ment for blood can­cers.

The mes­sage helped buoy the com­pa­ny’s stock to­day, send­ing shares up about 3%.

“With the de­fined com­po­si­tion treat­ment, we are able to get more re­pro­ducible da­ta about the ef­fects of the cells — both the ben­e­fi­cial im­pact against the can­cer and any side ef­fects to the pa­tient,” said Fred Hutch clin­i­cal re­searcher Stan Rid­dell, one of the se­nior au­thors of the pa­per, along with Dr. David Mal­oney. “We are then able to ad­just the dose to im­prove what we call the ther­a­peu­tic in­dex — im­pact against the tu­mor, with low­er tox­i­c­i­ty to the pa­tient.”

The ad­di­tion of flu­dara­bine to Juno’s lead CAR-T, JCAR015, was fin­gered for killing four pa­tients, a set­back for the biotech which trig­gered a brief but dam­ag­ing clin­i­cal hold by the FDA. The hold last­ed on­ly days, end­ing with the FDA sign­ing off on the biotech’s de­ci­sion to drop flu­dara­bine. But the hold end­ed up forc­ing Juno to de­lay its ex­pect­ed move to file for their first ap­proval back to 2018. Kite, mean­while, which is us­ing its own mix of T cells and Cy/Flu, has said it ex­pects to take the first batch of da­ta from its lead­ing study to the FDA af­ter an ini­tial re­view that comes in just a mat­ter of weeks.

This new study from Juno al­so rais­es ques­tions about its lead drug, JCAR015. If pa­tient out­comes are sig­nif­i­cant­ly low­ered by the ab­sence of flu­dara­bine, Juno’s first at­tempt at a com­mer­cial en­try against the com­pe­ti­tion could be se­vere­ly af­fect­ed.

CAR-Ts be­came a hot field a cou­ple of years ago, at­tract­ing hun­dreds of mil­lions in new in­vest­ments as the front run­ners raced to ad­vance new reme­dies for can­cer by adding a chimeric anti­gen re­cep­tor to a pa­tient’s T cells and then in­fus­ing them back in­to the pa­tient. But with Juno’s de­rail­ment and a re­cent de­ci­sion by No­var­tis to dis­solve its cell and gene ther­a­py unit and re­ab­sorb it in­to their big on­col­o­gy di­vi­sion, all eyes are on Kite now to see if it can claim the first ap­proval and mar­ket en­try.

The stakes are high.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.

The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 158,500+ biopharma pros reading Endpoints daily — and it's free.