US FDA investigating safety risk of CAR-T cancer therapies (updated)

2Seventy Bio

28/11/2023 23:19

(Adds details on treatment, comments by CAR-T scientist, ASCO
expert and Novartis, adds closing share prices, paragraphs 1-10,
13, 15-17)
    By Pratik Jain
       Nov 28 (Reuters) - The U.S. Food and Drug Administration
(FDA) said on Tuesday it was investigating cancer therapies made
by Gilead Sciences  GILD.O , Johnson & Johnson  JNJ.N , Novartis
 NOVN.S  and others over the risk of hospitalizations and death
due to a serious safety issue.
    The FDA said it had received reports of patients developing
a type of T-cell blood cancer after being treated with
genetically modified cells known as chimeric antigen receptor
T-cell therapies or CAR-T.
    The treatment generally involves extracting disease-fighting
white blood cells known as T-cells from a patient,
re-engineering them to attack cancer and infusing them back into
the body.
    Since 2017, six CAR-T cell therapies have been approved by
the FDA and all are for the treatment of blood cancers,
including lymphomas and some forms of leukemia.
    Maksim Mamonkin, a CAR-T expert at Baylor College of
Medicine's Center for Cell and Gene Therapy, who oversees
production of CAR-T treatments, said in clinical trials,
secondary cancers are "definitely not something that we
routinely see or something that we expect."
    "Obviously, when you start treating thousands of patients
with commercial products, that may become an issue just by
chance."
    Mamonkin said T-cell cancers can occur after patients
receive other cancer treatments such as chemotherapy. If
pre-cancerous cells were inadvertently collected and used to
make CAR-T treatments, that could result in secondary cancers.
    Dr. Julie Gralow, chief medical officer of the American
Society of Clinical Oncology, said, “Based on the available
data, the risk of T-cell malignancies due to CAR-T cell therapy
appears to be low."
    While such cancers have occurred in people who have received
CAR-T therapy, she said the causal relationship — whether by
chance or caused by the therapy — needs to be investigated.
    Approved cancer therapies in this class include Bristol
Myers Squibb's  BMY.N  Breyanzi and its partnered therapy,
Abecma, with 2seventy bio  TSVT.O .
    J&J unit Janssen and Legend Biotech's  LEGN.O  Carvykti,
Novartis AG's  NOVN.S  Kymriah, and Gilead unit Kite's Tecartus
and Yescarta are also a part of the investigation.
    Shares of Gilead closed down 0.6% at $74.51 on Tuesday.
Legend shares fell 2.6% to close at $59.99. Shares of Autolus
Therapeutics  AUTL.O  declined 4.8% to end at $4.55. 
    RBC analysts in a note said the concerns could be higher for
Novartis' Kymriah, and extremely rare for all the other marketed
CAR-Ts. 
    However, Mamonkin said the higher number of cases involving
Kymriah could be related to the fact that the treatment is more
commonly used in older adults, who are more prone to cancer.
    Novartis said in a statement that there is no evidence to
date that would change its confidence in Kymriah’s benefit or
risk profile and that it has not identified a causal
relationship between Kymriah and secondary malignancies. 
    The company added that it is "fully committed to patient
safety and will continue to work with the FDA." 
    Gilead said it had cooperated with the FDA on its request
for an analysis of the company's data, adding there was no
evidence that treatment with either of its two therapies had a
causal role in the development of new malignancies.
    "We are confident in the overall safety profile of both
Tecartus and Yescarta," Gilead told Reuters in an emailed
statement. 
    J&J and Bristol Myers did not immediately respond to
requests for comment.

 (Reporting by Pratik Jain and Christy Santhosh in Bengaluru,
and Michael Erman in New York and Julie Steenhuysen in Chicago
Editing by Krishna Chandra Eluri, Maju Samuel and Matthew Lewis)
 ((Pratik.Jain@thomsonreuters.com;))