Andy Plump (Jeff Rumans for Endpoints News @ JPM19)

MD An­der­son emerges with strong ev­i­dence for nat­ur­al killer cell ther­a­py, and Take­da looks like a win­ner

As far as bi­o­log­i­cal brand­ing goes, it’s hard to beat nat­ur­al killer cells.

Katay­oun Rez­vani

These im­mune re­spon­ders earned their moniker in the ’70s for their ap­par­ent abil­i­ty to kill virus­es and some tu­mor cells quick­ly and with­out ini­tial train­ing. And in re­cent years, as sci­en­tists be­gan re-en­gi­neer­ing T cells to at­tack eva­sive tu­mors and cre­at­ing the first CAR-T treat­ments, re­searchers start­ed se­ri­ous­ly ex­plor­ing how to do the same with nat­ur­al killers.

Now, MD An­der­son has emerged with some of the first clin­i­cal proof this can work. A team led by Katay­oun Rez­vani at­tached CARs – chimeric anti­gen re­cep­tors – for CD19 to nat­ur­al killer cells and in­ject­ed them in­to 11 pa­tients with ei­ther non-Hodgkin lym­phoma or chron­ic lym­pho­cyt­ic leukemia. Sev­en of them had a com­plete re­sponse; their tu­mors van­ished.

The news is a step for­ward in nat­ur­al killer cell re­search and for can­cer cell ther­a­py as a field. It’s al­so a good sign for Take­da, who li­censed the ther­a­py for an undis­closed sum in No­vem­ber as part of a broad push to reignite an ail­ing R&D en­gine. Re­sults from the Phase I/II study were pub­lished in the New Eng­land Jour­nal of Med­i­cine.

Much of the in­ter­est around nat­ur­al killer cell ther­a­py, or CAR-NK, stems from their po­ten­tial as a form of “off-the-shelf CAR-T.” CAR-T treat­ments such as Kite Phar­ma’s Yescar­ta and No­var­tis’ Kym­ri­ah have dis­ap­point­ed com­mer­cial­ly be­cause they have to be done us­ing a pa­tient’s own cells, set­ting off a long and cost­ly process that both lim­it the num­ber of pa­tients it can help and po­ten­tial prof­it. You can’t use donor T cells now in part be­cause it would like­ly trig­ger graft-ver­sus-host dis­ease, al­though there are on­go­ing ef­forts to get around that and make an al­lo­genic CAR-T.

But for­eign nat­ur­al killer cells don’t cause graft-ver­sus-host dis­ease. So rather than draw­ing mil­lions of a pa­tient’s cells, treat­ing them with a re­cep­tor over weeks or months and then rein­ject­ing them in­to a pa­tient, Rez­vani could use do­nat­ed um­bil­i­cal cord blood. For 9 of the 11 pa­tients, the team found a par­tial donor match and for the last 2, the cells were com­plete­ly mis­matched. None of the pa­tients ex­pe­ri­enced GVHD.

“We have shown that we can man­u­fac­ture hun­dreds of dos­es of CAR NK cells from a sin­gle unit of cord blood,” Rez­vani said in De­cem­ber. “Ul­ti­mate­ly, our plan is to freeze and store these CAR NK cells in a cell bank so that when a pa­tient comes to the clin­ic, we can take those CAR NK cells im­me­di­ate­ly from the bank to treat the pa­tients, mak­ing this a tru­ly off-the-shelf-prod­uct.”

Rez­vani’s team took iso­lat­ed nat­ur­al killers cells from the um­bil­i­cal cord blood, ge­net­i­cal­ly mod­i­fied them to iden­ti­fy can­cers that would oth­er­wise evade the cells, “ar­mored” the nat­ur­al killers with IL-15 and fi­nal­ly in­ject­ed them in­to 11 pa­tients who had al­ready been through a me­di­an of 4 lines of ther­a­py. Most be­gan to re­spond with­in 30 days. Af­ter 13.8 months, sev­en were still dis­ease-free, al­though the re­searchers said the ac­tu­al du­ra­tion of re­sponse couldn’t be mea­sured be­cause pa­tients went on oth­er ther­a­pies af­ter re­ceiv­ing the CAR-NK.

The oth­er ben­e­fit of nat­ur­al killer cells is that they ap­pear to not cause the main tox­i­c­i­ty that CAR-T can cause: cy­tokine re­lease syn­drome, a po­ten­tial­ly dead­ly sce­nario in which the mod­i­fied im­mune cells re­lease bil­lions of in­flam­ma­tion-caus­ing mol­e­cules. This syn­drome is thought to be caused by IL-6, and nat­ur­al killers give off far less of that pro­tein than T cells.

The ther­a­py could reach pa­tients soon, at least by the stan­dards of ear­ly-stage can­cer stud­ies. Take­da R&D chief Andy Plump told End­points News in No­vem­ber they were look­ing to ini­ti­ate a piv­otal tri­al in 2021.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

FDA spells out how can­cer drug de­vel­op­ers can use one tri­al for both ac­cel­er­at­ed and full ap­provals

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

Lat­est on ul­tra-rare dis­ease ap­proval; Pos­i­tive, if mixed, signs for Bio­gen's ALS drug; Clay Sie­gall finds a new job; and more

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Over the last four years, we’ve honored 80 women whose extraordinary accomplishments have changed the game in biopharma R&D. You can now nominate someone to be highlighted in this year’s special report. Details are here.

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No­vo Nordisk oral semaglu­tide tri­al shows re­duc­tion in blood sug­ar, plus weight loss

Novo Nordisk is testing higher levels of its oral version of its GLP-1, semaglutide, and its type 2 diabetes trial results released today show reductions in blood sugar as well as weight loss.

In the Phase IIIb trial, Novo compared its oral semaglutide in 25 mg and 50 mg doses with the 14 mg version that’s currently the maximum approved dose. The trial looked at how the doses compared when added to a stable dose of one to three oral antidiabetic medicines in people with type 2 diabetes who were in need of an intensified treatment.

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Ly­me vac­cine test com­ple­tion is pushed back by a year as Pfiz­er, Val­ne­va say they'll ad­just tri­al

Valneva and Pfizer have adjusted the end date for the Phase III study of their investigational Lyme disease vaccine, pushing it back by a year after issues at a contract researcher led to thousands of US patients being dropped from the test.

In a March 20 update to, Valneva and Pfizer moved the primary completion date on the trial, called VALOR, from the end of 2024 to the end of 2025.

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Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

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FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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Sijmen de Vries, Pharming CEO

FDA ap­proves Pharm­ing drug for ul­tra-rare im­mun­od­e­fi­cien­cy dis­ease

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.

Stuart Peltz, former PTC Therapeutics CEO

Stu­art Peltz re­signs as PTC Ther­a­peu­tics CEO af­ter 25 years

Stuart Peltz, the longtime CEO of PTC Therapeutics who’s led the rare disease drug developer since its founding 25 years ago, is stepping down.

Succeeding him in the top job is Matthew Klein, who joined PTC in 2019 and was promoted to chief operating officer in 2022. In a call with analysts, he said the CEO transition has been planned for “quite some time” — in fact, as part of it, he gave the company’s presentation at the JP Morgan healthcare conference earlier this year.

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