Press Release: Novartis announces NEJM publication of updated analysis from ELIANA trial showing longer-term durable remissions with Kymriah(TM) in children,...

Novartis International AG / Novartis announces NEJM publication of

updated analysis from ELIANA trial showing longer-term durable

remissions with Kymriah(TM) in children, young adults with r/r ALL.

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-- Analysis of 75 patients with median follow-up of more than a year

demonstrated an overall remission rate of 81%

-- Event-free survival and overall survival at six months were 73% and 90%,

with median duration of remission not reached

-- Kymriah was detected in patients up to 20 months, demonstrating long-term

persistence

-- Novartis is committed to bringing Kymriah to more patients with a

regulatory application currently under review by the EMA for r/r ALL and

r/r DLBCL based on Novartis global clinical trial program, including

ELIANA

The digital press release with multimedia content can be accessed here:

https://novartis.gcs-web.com/Novartis-announces-NEJM-publication-of-updated-analysis-from-ELIANA-trial-showing-longer-term-durable-remissions-with-Kymriah-in-children-young-adults-with-r-r-ALL

Basel, January 31, 2018 - Novartis today announced updated results from

the pivotal ELIANA clinical trial of Kymriah(TM) (tisagenlecleucel),

formerly CTL019, in relapsed or refractory (r/r) pediatric and young

adult patients with B-cell acute lymphoblastic leukemia (ALL) have been

published in The New England Journal of Medicine (NEJM). New data

include longer-term follow-up and efficacy in 75 infused patients,

analysis of expansion and persistence of Kymriah, and longer-term

safety. Kymriah became the first chimeric antigen receptor T (CAR-T)

cell therapy to receive regulatory approval in August 2017, when it was

approved by the US Food and Drug Administration (FDA) for the treatment

of patients up to 25 years of age with B-cell precursor ALL that is

refractory or in second or later relapse, based on previous results from

the ELIANA study, which was conducted in collaboration with the

University of Pennsylvania (Penn) and Children's Hospital of

Philadelphia (CHOP).

In the analysis of 75 infused patients with three or more months of

follow-up, Kymriah demonstrated an overall remission rate of 81% (95%

CI: 71% - 89%). Sixty percent of patients achieved complete remission

(CR) and 21% of patients achieved CR with incomplete blood count

recovery (CRi), with no minimal residual disease (MRD) detected among

all responding patients (95% [58/61] by day 28). Median follow-up was

13.1 months.

"Kymriah, the first FDA-approved CAR-T cell therapy, has shown the

potential to be a definitive therapy, providing early, deep and durable

remissions for children and young adults with relapsed or refractory ALL,

" said Samit Hirawat, MD, Head, Novartis Oncology Global Drug

Development. "These data are a testament to our commitment at Novartis

for continued CAR-T cell therapy research to bring this therapy to as

many patients as possible."

Among patients who achieved CR/CRi, median duration of response was not

reached. Remissions were durable with six-month relapse-free survival of

80%. Event-free survival was 73% at six months (95% CI: 60%-82%) and 50%

at 12 months (95% CI: 35%-64%), with median event-free survival not

reached. Overall survival in the 75 infused patients was 90% (95% CI:

81%-95%) at six months, and 76% (95% CI: 63%-86%) at 12 months. Kymriah

was detected in patients up to 20 months. Median persistence of Kymriah

was 168 days (range: 20-617; n=60 patients with CR/CRi) at data cutoff.

All responding patients demonstrated B-cell aplasia (a low number of or

absent B-cells), an on-target effect of treatment with Kymriah, and most

received immunoglobulin replacement per local practice. Evaluable

patients with a response at day 28 had a median time to maximum

expansion of 10 days (5.7-28 days; n=60), whereas six patients with no

response had a median time to maximum expansion of 20 days (13-63 days).

Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen

receptor, which has shown to enhance early cellular expansion and

long-term endurance of CAR-T cells.

"We continue to be encouraged by the results demonstrated with Kymriah

in a patient population who previously had limited treatment options,

and now have the potential for durable remissions translating into

longer-term survival," said lead study author Shannon L. Maude, MD, PhD,

Assistant Professor of Pediatrics, at Children's Hospital of

Philadelphia and Perelman School of Medicine at the University of

Pennsylvania. "Not only does this longer-term follow-up from the ELIANA

study reinforce that this is a potentially paradigm-changing treatment,

but it also contributes to the growing body of evidence which shows the

critical role of cell function, expansion and ongoing persistence of

Kymriah associated with the durability of clinical response."

Any grade treatment-related adverse events (AE) occurred in 95% of

patients, with the most common non-hematologic AEs being cytokine

release syndrome (CRS; 77%), pyrexia (40%), decreased appetite (39%),

febrile neutropenia (36%) and headache (36%). Seventy-three percent of

patients experienced a grade 3/4 treatment-related AE. CRS, a known

complication of Kymriah that may occur when engineered cells become

activated in the patient's body, occurred in 77% of patients. Forty-six

percent of patients experienced grade 3/4 CRS (grade 3: 21%; grade 4:

25%), using the Penn Grading Scale, a rigorous scale for grading CRS.

CRS was managed globally using prior site education on implementation of

the CRS treatment algorithm. Thirty-five of 75 infused patients (47%)

were admitted to the intensive care unit for management of CRS.

Neurological events occurred in 40% of patients within eight weeks of

infusion, and 13% (n=10) of patients had grade 3, which were managed

with best supportive care. No incidence of grade 4 neurological events

or cerebral edema was reported. Eighteen patients (24%) received Kymriah

in the outpatient setting. To support safe patient access, Kymriah is

only available through a network for certified treatment centers

throughout the country which are fully trained on the use of Kymriah and

appropriate patient care.

ELIANA is the first pediatric global CAR-T cell therapy registration

trial, examining patients in 25 centers in the US, Canada, Australia,

Japan and the EU, including: Austria, Belgium, France, Germany, Italy,

Norway and Spain, demonstrating effective distribution of CTL019 across

four continents using a global supply chain. 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.

A Marketing Authorization Application for Kymriah for the treatment of

children and young adults with r/r B-cell ALL and adult patients with

r/r diffuse large B-cell lymphoma (DLBCL) who are ineligible for

autologous stem cell transplant (ASCT) is currently under review by the

European Medicines Agency (EMA). A supplemental Biologics License

Application is also under review by the FDA for Kymriah for the

treatment of adult patients with r/r DLBCL who are ineligible for or

relapse after ASCT. Additional filings beyond the US and EU are

anticipated in 2018.

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.

About Kymriah Manufacturing

Kymriah will be manufactured for each individual patient using their own

cells at the Novartis Morris Plains, New Jersey facility. In the US, the

target turnaround time for manufacturing Kymriah in the commercial

setting is 22 days. The reliable and integrated manufacturing and supply

chain platform for Kymriah allows for an individualized treatment

approach on a global scale. The process includes cryopreservation of a

patient's harvested (or leukapheresed) cells, giving treating physicians

and centers the flexibility to initiate therapy with Kymriah based on

the individual patient's condition. Building on the company's experience,

having manufactured CAR-T cells for over 300 patients from 11 countries

across various indications in clinical trials, it has demonstrated a

high-quality and reproducible product. Novartis continues to advance its

CAR-T manufacturing expertise and make investments to support the

anticipated demand to meet the needs of patients. Novartis continues to

advance its CAR-T manufacturing expertise in Morris Plains where we have

been supplying CAR-T cells for global clinical trials and where we

continue to invest in support of the anticipated demand to meet the

needs of patients.

Kymriah(TM) (tisagenlecleucel) Important Safety information

The full prescribing information, including Boxed WARNING, for Kymriah

can be found at: https://www.pharma.us.novartis.com/sites/

www.pharma.us.novartis.com/files/kymriah.pdf

Kymriah may cause side effects that are severe or life-threatening, such

as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients

with CRS may experience symptoms including high fever, difficulty

breathing, chills/shaking chills, severe nausea, vomiting and diarrhea,

severe muscle or joint pain, very low blood pressure, or

dizziness/lightheadedness. Patients may be admitted to the hospital for

CRS and treated with other medications.

Patients with neurological toxicities may experience symptoms such as

altered or decreased consciousness, headaches, delirium, confusion,

agitation, anxiety, seizures, difficulty speaking and understanding, or

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January 31, 2018 17:00 ET (22:00 GMT)