Novartis International AG / Primary analysis results from Novartis
pivotal JULIET trial show Kymriah (tisagenlecleucel) sustained
complete responses at six months in adults with r/r DLBCL, a
difficult-to-treat cancer . Processed and transmitted by Nasdaq
Corporate Solutions. The issuer is solely responsible for the content of
this announcement.
-- At six months, 30% of patients treated with Kymriah were in complete
response, with a 74% relapse-free rate after onset of response; median
duration of response was not reached
-- Grade 3/4 neurologic events occurred in 12% of patients; Grade 3/4 CRS
occurred in 23% of treated patients using the Penn Grading Scale and was
managed by protocol-specific algorithm
-- More than a quarter of patients received Kymriah in outpatient setting
during JULIET trial
-- Cost-effectiveness and societal value of Kymriah in pediatric and young
adult patients with r/r B-cell ALL to be presented at ASH
The digital press release with multimedia content can be accessed here:
https://novartis.gcs-web.com/Primary-analysis-results-from-Novartis-pivotal-JULIET-trial-show-Kymriah-tisagenlecleucel-sustained-complete-responses-at-six-months-in-adults-with-r-r-DLBCL-a-difficult-to-treat-cancer
Basel, December 10, 2017 - Novartis today announced updated results from
the JULIET clinical trial demonstrating sustained responses with
Kymriah (tisagenlecleucel) suspension for intravenous infusion,
formerly CTL019, in adult patients with relapsed or refractory (r/r)
diffuse large B-cell lymphoma (DLBCL). The data from this pivotal trial,
led by researchers from the University of Pennsylvania (Penn), show an
overall response rate (ORR) of 53% (95% confidence interval [CI], 42% -
64%; p<0.0001), with 40% achieving a complete response (CR) and 14%
achieving a partial response (PR) among 81 infused patients with three
or more months of follow-up or earlier discontinuation. At six months
from infusion, the ORR was 37% with a CR rate of 30%. The median
duration of response was not reached. Results from this study of Kymriah,
the first-ever FDA-approved chimeric antigen receptor T cell (CAR-T)
therapy, were included in the US and EU regulatory filings for Kymriah
in r/r DLBCL and will be presented in an oral presentation at the 59th
American Society of Hematology (ASH) annual meeting (Abstract #577;
Monday, December 11, 7:00 AM EST)[1].
"At the time of trial enrollment, these patients with DLBCL had been
through multiple rounds of chemotherapy and many had unsuccessful stem
cell transplants, leaving them with few options and a poor prognosis,"
said the study's principal investigator Stephen J. Schuster, MD, the
Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic
Leukemia and Lymphoma Clinical Care and Research in the University of
Pennsylvania's (Penn) Perelman School of Medicine and director of the
Lymphoma Program at the Abramson Cancer Center. "With tisagenlecleucel,
we have been able to significantly increase their chance of achieving
and maintaining a sustained response without stem cell transplant,
demonstrating the therapy's benefit in the treatment of this lethal
blood cancer."
At month three, the CR rate was 32% and the PR rate was 6%, which
remained consistent to month six (30% CR, 7% PR). Response rates were
also consistent among prognostic subgroups, including patients who
received prior autologous stem cell transplant (ASCT) and those with a
subtype of DLBCL known as double-hit lymphoma, who historically have
poor outcomes. No patients in response following treatment with Kymriah
proceeded to stem cell transplant[1].
In the JULIET study, the relapse-free probability at six months after
first response was 74% (95% CI, 52%-87%), and median duration of
response was not reached. Median overall survival was also not reached
(95% CI: 6.5 months to NE [not estimable]), and the median time from
infusion to data cutoff was 5.6 months[1].
"While immediate response to treatment is a marker for efficacy,
patients and physicians need treatment options that provide sustained
responses over time with a consistent safety profile," said Samit
Hirawat, MD, Head, Novartis Oncology Global Drug Development. "We look
forward to continuing to work with health authorities to bring Kymriah
to patients with relapsed or refractory DLBCL."
In the JULIET study, cytokine release syndrome (CRS) occurred in 58% of
all treated patients, with 23% of patients experiencing grade 3/4 CRS
(15% grade 3; 8% grade 4) using the Penn Grading Scale, a rigorous scale
for grading CRS. CRS is a known complication of CAR-T therapy that may
occur when the engineered cells become activated in the patient's body.
CRS was managed globally using prior site education on implementation of
the CRS treatment algorithm[1].
Twenty one percent of patients experienced any grade neurologic events,
and 12% of patients had grade 3/4 neurologic adverse events, which were
managed with supportive care. Grade 3/4 cytopenias lasting more than 28
days, grade 3/4 infections and grade 3/4 febrile neutropenia occurred in
27%, 20% and 13% of patients, respectively. Three patients died from
disease progression within 30 days of infusion. There were no deaths
attributed to Kymriah, CRS or neurological events. No cerebral edema
events were reported[1].
In the JULIET trial, 26 patients (26%) were infused in the outpatient
setting; of those, 20 patients (77%) remained outpatient for three or
more days after infusion. Forty-three patients discontinued before
infusion and the majority did so due to rapid progression of their
disease or deterioration in their clinical status. This reflects the
acute and progressive nature of relapsed or refractory DLBCL. Only 9 of
147 (6.1%) enrolled patients could not be infused due to inability to
manufacture an adequate dose of CAR-T cells. Over the course of JULIET,
with continuous process improvements, manufacturing success rate
improved to 97% for the last 30 patients.
JULIET is the first multi-center global registration study for Kymriah
in adult patients with r/r DLBCL and the second global CAR-T cell
therapy trial, following the Novartis ELIANA study of Kymriah in
children and young adults with r/r B-cell acute lymphoblastic leukemia
(ALL). JULIET was conducted in collaboration with Penn and enrolled
patients from 27 sites in 10 countries across the US, Canada, Europe,
Australia and Japan. In 2012, Novartis and Penn entered into a global
collaboration to further research, develop and commercialize CAR-T cell
therapies, including Kymriah, for the investigational treatment of
cancers.
The results from JULIET build upon a pilot study of Kymriah in r/r DLBCL
and follicular lymphoma published online today in the New England
Journal of Medicine, which was led by and conducted at Penn and
supported by Novartis and grants from the National Institutes of Health,
as well as through philanthropic support. Among patients with r/r DLBCL,
the study demonstrated an ORR and safety profile similar to results seen
in JULIET. The study demonstrated sustained remissions at a follow up of
28.6 months among patients who responded at six months[2].
In April 2017, the US Food and Drug Administration (FDA) granted
Breakthrough Therapy designation to Kymriah based on data from the
JULIET study. In October 2017, Novartis submitted an application to the
FDA for Kymriah in adult patients with r/r DLBCL who are ineligible for
or relapse after ASCT, followed shortly by an application to the
European Medicines Agency (EMA) in November for Kymriah for the
treatment of adult patients with r/r DLBCL who are ineligible for ASCT,
and for children and young adults with r/r B-cell ALL. Additional
filings beyond the US and EU are anticipated in 2018.
Economic and Societal Value of Kymriah in ALL Presented at ASH
Results of a cost-effectiveness analysis of Kymriah for the treatment of
r/r B-cell ALL in the US will be presented in an oral presentation at
the meeting (Abstract #609; Monday, December 11, 7:30 AM EST).
The analysis showed that, based on the current US list price of
$475,000, Kymriah is cost-effective compared to standard of care. The
analysis compared the life years and quality-adjusted life years gained
with Kymriah compared to clofarabine monotherapy, clofarabine
combination therapy, blinatumomab, other salvage chemotherapies and
allogeneic stem cell transplant. Quality-adjusted life years is a
measure of value of health outcomes based on disease burden, including
both the quality and quantity of life lived[3].
In addition, results of another analysis to determine the potential
societal value of Kymriah to patients with r/r ALL in the United Kingdom
were presented in a poster presentation at the meeting (Abstract #1330;
Saturday, December 9, 5:30 PM EST).
To quantify the societal value of Kymriah, the analysis looked at the
economic value of the incremental quality adjusted life years gained
along with the patient's expected productivity using nationally
representative data on employment rates and earnings. Results show that
therapies such as Kymriah have the potential to provide benefit to
patients and society, particularly through gains in survival,
contributing to productivity[4].
About Kymriah
In August 2017, Kymriah became the first available chimeric antigen
receptor T cell (CAR-T) therapy when it received FDA approval for
children and young adults with B-cell acute lymphoblastic leukemia (ALL)
that is refractory or has relapsed at least twice. Kymriah is a novel
immunocellular therapy and a one-time treatment that uses a patient's
own T cells to fight cancer. Kymriah uses the 4-1BB costimulatory domain
in its chimeric antigen receptor to enhance cellular expansion and
persistence.
About Kymriah Manufacturing
Kymriah will be manufactured for each individual patient using their own
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