CAR-T free webinar Oct. 3, a new CAR-T entrant, etc…

CAR-Therapy: A New Twist on Transplants (free webinar Oct. 3 from the Blood & Marrow Transplant Information Network)

A long article (you must navigate across several pages) that covers the topic well…

CAR T-cell therapy approval huge step for oncology, but only ‘beginning of story’

CAR-T Cell Therapy Is Here To Stay

Autolus, a British startup that has made news for raising $$ for their new CAR-T trials in lymphoma and multiple myeloma:

UK start-up Autolus starts ‘living medicine’ cancer trials

Three CAR-T cell therapy studies announced from UK start-up Autolus – EPM Magazine

British biotech joins race to find ‘living medicines’ for cancer after cash injection

‘Living medicine’ cancer therapy starts clinical trials – GOV.UK

Autologous CAR-T Cell Manufacturing: Current Standing and Future Directions | GEN

Unpacking what $475,000 means (Slide presentation from Memorial Sloan-Kettering that turned up in social media)

(7) CAR-T – Welcome to the Jungle! | LinkedIn

Why Fred Hutch’s chief is enlisting techies to defeat cancer by 2025 – GeekWire




CAR-T: The road ahead (controlling costs, new products and innovations, etc.)

“The cost of the leukemia treatment, called Kymriah, is ‘dramatically higher’ than other such complex treatments, and the health-care system isn’t ready to pay for it, Steve Miller, chief medical officer at Express Scripts Holding Co., said Thursday in a blog post on his company’s website.”

Novartis’s $475,000 Price on Cancer Therapy Meets Resistance – Bloomberg

P.S.  In the “it’s a small world” department, the two companies mentioned above are Novartis and Express Scripts.  As it happens, two companies I worked at a few years before being diagnosed with lymphoma were Medco (acquired by Express Scripts) and Sandoz (merged with Ciba-Geigy to become Novartis).

Somehow (Twitter?), I stumbled on this site, Prescription Drug Prices and More.  It seems to be run by a pharmacist named Bertram Drachtman.  I found these two recent posts interesting:

Off The Shelf Car-T and Gene Therapy – Prescription Drug Prices and More

Car-T Therapy. A “Miracle Cure For Cancer In Our Time”? – Prescription Drug Prices and More

Why CAR-T Therapies Don’t Work for Everyone Yet | GEN

The CAR-T landscape going forward…

Evolution Bioscience | The CAR-T Revolution: Gilead’s Acquisition of Kite Pharma & FDA Approval of Novartis’ Kymriah Signal Tipping Point for Promising Cancer Immunotherapies

A New Model T on the Horizon?


A very technically detailed explanation of the ins-and-outs of CAR-T, posted on Quora, apparently from someone with a PhD in Cancer Immunotherapy.  A fascinating read…

Tirumalai Kamala’s answer to Why didn’t the anti-CD19 CAR-T immunotherapies from Novartis or Kite suffer from neurotoxicity adverse events as the ones from Juno did? – Quora

A reminder that CAR-T therapies, while potentially curative, “carry unique, potentially lethal side effects…”

Researchers compose guidelines for handling CAR-T cell side effects

…behind the scenes, there’s another race going on: the effort to develop efficient manufacturing for CAR-T therapeutics.

The Other CAR-T Race: Manufacturing – Bioprocess Technology Consultants

The publication below from the Journal of the AMA (JAMA) made headlines recently in places like the New York Times and NPR, especially in light of Novartis’ recent pricing of their FDA-approved Kymriah CAR-T therapy at $475,000.  The crux of the issue seems to be how to fairly compensate for all the “sunk costs” of failed drugs, a topic I heard about often during my employment at Sandoz (which ironically is now Novartis).  It seems a bit like the argument made by record companies back in the ‘80’s to charge $17 per CD, to compensate for their investments in albums that didn’t sell in the millions. This will certainly remain a hot topic…

Cost of Developing a Single Cancer Drug | Clinical Pharmacy and Pharmacology | JAMA Internal Medicine | The JAMA Network

Stories on Juno Therapeutics, the other CAR-T competitor besides Novartis and Kite.  (My CAR-T therapy at MSK in July 2015 was in partnership with Juno)

“The Seattle biotech company lost the race to be first with an approved treatment using the revolutionary approach called CAR-T cell therapy. But it still aims to be the best in class…”

Juno Therapeutics ready for another round in war on cancer | The Seattle Times

On CAR-T’s Edge, Seattle Researchers Plot to Bypass Novartis Therapy | Xconomy

Considering investing in CAR-T?

“Juno has nine different drugs being tested in eleven different trials, all of which tap into the recently-validated science of CAR-T therapies. The race for them is only apt to heat up as time marches on, with some observers suggesting the CAR-T therapy market could be worth $8.5 billion by 2028.”

Yes, Juno Therapeutics (JUNO) Just Became a Great CAR-T Trade

September 2017 news updates (updated 11:45am)

A great piece from the New England Journal of Medicine detailing how we got here.  (This has been all over the web.) …

Comprehensive coverage of CAR-T from the NIH:

Patient Death Won’t Slow Research on “Off-the-Shelf” Immune Cells to Treat Cancer – MIT Technology Review

A plethora of new cancer treatments is under development
There will be more cures, and they will be expensive

Kymriah and the CAR-T roller coaster – MedCity News

By Jamie Reno, a longtime fNHL survivor himself.  Jamie really covers it in this piece:

CAR T-cells: an exciting frontier in cancer therapy – The Lancet

Click the “Download as PDF” for a free, informative CAR-T wall chart:

Stories about that $475,000 price tag for Novartis CAR-T (updated 11:45am):

    CAR-T in the Courts | GEN
    Patent Disputes Bring Immunotherapy Technology and Patent Review Process into Focus

    T-Cell Pioneer Carl June Acknowledges Key Ingredient Wasn’t His – MIT Technology Review (March 2016)

    5 Significant Developments With CAR-T Therapy

    CAR-T Mania: Could Juno Therapeutics Get Acquired Next? | Fox Business

    A CAR-T Conversation with Gregg Sando, CEO of Cell Medica
    The CAR-T Race is Far from Over: This CEO is Exploring a New Avenue


    Gene therapy for cancer halted after patient death

    Gene therapy for cancer halted after patient death

    11 September 2017

    By Ebtehal Moussa

    Appeared in BioNews 917

    Two trials assessing gene therapy for blood cancer have been put on hold by the US Food and Drug Administration (FDA), following a patient fatality.

    The therapy, known as ‘off-the-shelf’ CAR-T immunotherapy, used genetically modified immune system T cells to target cancer, yet unlike other trials the cells were taken from a healthy donor instead of the patient. It was hoped this therapy would prove easier and less expensive to produce.

    Allogeneic production of CAR-T cells is cost-effective and results in remarkable off-the-shelf product, capable of being distributed worldwide’, the manufacturer Cellectis had suggested in a video presentation.

    The early-stage trials of the therapy, called UCART123, aimed to treat two types of blood cancer, blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukaemia (AML), in patients who did not respond to typical treatment or relapsed.

    The 78-year old male patient who died was first to be treated in the BPDCN study. He experienced side effects in the form of lung infection and moderate cytokine release syndrome (CRS) at day five, severe CRS and blood vessel leakage on day eight, and death on day nine. CRS results from the excessive release of immune components called cytokines from targeted cancer cells and immune system cells.

    The first patient in the AML study, a 58-year old female patient, received the same treatment at the same dose, and experienced similar side effects. Although intensive care treatment resolved the side effects, the AML study has also been put on hold until the development of appropriate safety measures.

    Two days following the reported patient fatality, the FDA made a recommendation to lower the immunotherapy and supporting drug dosage.

    ‘Cellectis is working closely with the investigators and the FDA in order to resume the trials with an amended protocol including a lowered dosing of UCART123,’ the company said in a statement.

    Cellectis’s shares fell by 23 percent following the FDA’s notice. It is not the first to report patient death through CAR-T therapy trials. In March 2017, the pharmaceutical company Juno Therapeutics reported five patient deaths in response to personalised CAR-T therapy targeting acute myeloid leukaemia, a type of blood cancer. Similarly, Kite Pharma’s trial on aggressive non-Hodgkin lymphoma has reported one patient death.


    Some of the logistics, manufacturing and pricing details in the aftermath of Novartis gaining FDA approval of CAR-T

    Wow, where to start? So much has been written about CAR-T while I was away this past week. The stories below just scratch the surface. I’m sure I’ll have more in the next few days. So, in no particular order…

    Details of Novartis’ manufacturing process:


    Kite’s manufacturing process (Kite Pharmaceuticals anticipates being next to receive FDA approval for their CAR-T therapy):


    From Novartis, a video of its manufacturing process:


    About that $475,000 price tag … This was guaranteed to stir controversy. Novartis’ rationale is that CAR-T can supplant an allogeneic stem cell transplant (SCT), which can cost $550 – 800K, with greater mortality risk and probably less curative potential.  Also controversial is Novartis’ decision not to refund the cost if the patient has achieved a Complete Remission (CR) in the first month, when many patients may relapse afterwards.  A 3-month or even 6-month CR would be more indicative of a potential cure.


    Speaking of costs, the twittersphere is buzzing about this quote from Dr. Carl June at U. Penn back in 2012:

    Dr. June said that producing engineered T-cells costs about $20,000 per patient — far less than the cost of a bone-marrow transplant. Scaling up the procedure should make it even less expensive, he said, but he added, “Our costs do not include any profit margin, facility depreciation costs or other clinical care costs, and other research costs.”


    A profile of Carl June and his immunotherapy research in the Wall Street Journal:


    Some of CAR-T’s success can be attributed to insights gained by the publicly-funded National Institutes of Health (NIH):


    From Memorial Sloan-Kettering – from transplants to breakthroughs such as Steven Rosenberg at the NIH, etc…


    This didn’t get quite as much press, but the FDA simultaneously “approved an expanded indication for Actemra to treat CAR T cell-induced severe or life-threatening CRS in patients ages two and older on Wednesday”. Actemra is an IL-6 inhibitor typically used to treat Rheumatoid Arthritis.  It was famously used as a last resort to reduce the CRS and thereby save the life of CAR-T’s first patient, 6-year-old Emily Whitehead, at U. Penn in 2012.  I’m now planning to ask my own oncologist, during my next visit in January, whether it was ever considered to control my CRS after my CAR-T infusion in July 2015.  (I spent five days in ICU after my infusion.)


    I know I’ve posted about this before.  The Fred Hutchinson Cancer Center in Seattle is attempting to bypass the entire T-cell collection and manufacturing process by modifying the patient’s T cells in situ:


    From journalist Michelle Cortez at Bloomberg News… it details some other attempts to bypass the $$ T-cell collection and manufacturing process, including equipping the hospitals and cancer centers to conduct it themselves:




    This Science Magazine article contains links to other interesting articles…


    From AP News (links to other CAR-T demo videos):

    FDA has just approved the first CAR-T therapy!

    Truly a momentous day in the long and winding history of this life-saving therapy.  It’s initially approved for Acute Lymphoblastic Leukemia (ALL).  Can approval for Lymphoma be far behind?

    Press Announcements > FDA approval brings first gene therapy to the United States

    Novartis wins a landmark FDA approval with first CAR-T cancer drug

    EP Vantage – World’s first CAR-T approval sweeps away more cell therapy doubts

    Kite Seeks EU Approval for CAR T-Cell Therapy in 3 Lymphoma Subtypes (August 3, 2017)

    Kite Pharma submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) requesting the approval of its CAR T-cell therapy, axicabtagene ciloleucel, as treatment for patients with certain lymphomas.

    The include relapsed or refractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL), who cannot receive autologous stem cell transplants.

    This is the first application for a CAR T-cell therapy ever submitted to the EMA.

    Full article: