Press Release: Novartis announces longer-term analyses from pivotal Kymriah(R) trials that showed durable responses are maintained in patients with advanced ...

Novartis International AG / Novartis announces longer-term analyses from

pivotal Kymriah(R) trials that showed durable responses are maintained

in patients with advanced blood cancers. Processed and transmitted by

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this announcement.

-- In the updated analysis from ELIANA, Kymriah demonstrated an 82%

remission rate within 3 months in pediatric patients with r/r ALL;

relapse-free survival was 62% at 24 months, with median duration of

remission still not reached[1]

-- The longer follow-up from the JULIET study in patients with r/r DLBCL

reported 64% relapse-free probability and a 43% probability of overall

survival at 18 months, with median duration of response still not

reached[2]

-- The safety profiles observed in both longer-term analyses remained

consistent with previously reported results, with no emergence of new

safety signals

-- ASH presentations demonstrate the Novartis commitment to understanding

the long-term potential of Kymriah in transforming the treatment of ALL

and DLBCL

Basel, December 1, 2018 - Novartis today announced longer-term analyses

of both ELIANA and JULIET, the pivotal clinical trials of Kymriah

(tisagenlecleucel) in children and young adult patients with relapsed or

refractory (r/r) acute lymphoblastic leukemia (ALL) and adult patients

with r/r diffuse large B-cell lymphoma (DLBCL), respectively. In these

analyses, Kymriah continued to demonstrate strong efficacy with durable

responses and maintained a consistent and well-characterized safety

profile. These data are being presented at the 60(th) American Society

of Hematology (ASH) annual meeting. Additionally, today, the New England

Journal of Medicine published online the 14-month results from JULIET,

the study led by the Abramson Cancer Center at the University of

Pennsylvania[3].

"After bringing the first CAR-T cell therapy to patients, Novartis is

committed to continue our pioneering efforts to reimagine the treatment

paradigm for patients with aggressive blood cancer," said Samit Hirawat,

MD, Head, Novartis Oncology Global Drug Development. "These analyses

underscore the longer-term durability of response with Kymriah and its

consistent safety profile, reinforcing our belief in the potential for

CAR-T cell therapy to extend the lives of patients with these advanced

B-cell malignancies."

In the 24-month follow-up analysis of the ELIANA study in children and

young adults with r/r B-cell ALL, Kymriah demonstrated deep and durable

responses without subsequent therapy in a significant portion of

patients in this population. Among 79 evaluable patients, who were

followed for at least three months or discontinued earlier, 82% (95%

confidence interval [CI], 72% - 90%) achieved complete response (CR) or

CR with incomplete blood count recovery (CRi) within three months of

infusion; and among these responding patients, 98% had negative minimal

residual disease (MRD-). The relapse-free survival rate was 62% at 24

months; and the median duration of remission (mDOR) and median overall

survival (mOS) remained unreached, signifying responses are deep and

sustained, and further reinforcing the potential for Kymriah to be a

definitive therapy for many patients. The probability of OS was 76% (95%

CI, 65% - 85%) at 12 months and 66% (95% CI, 58% - 79%) at 24 months.

The safety profile observed in this updated analysis was consistent with

previously reported results, with no emergence of new safety signals.

Grade 3/4 cytokine release syndrome (CRS) - as defined by the rigorous

Penn Grading Scale - occurred in 49% of patients. Within eight weeks of

infusion, 13% of patients experienced grade 3 neurological events, with

no grade 4 events or cerebral edema[1]. These updated data will be

presented in an oral session at the ASH annual meeting (Abstract # 895;

Monday, December 3, 4:30 PM PST).

"Our group has devoted a great deal of attention to advancing treatment

options for children and young adults with B-cell ALL. This two-year

analysis is an exciting milestone for the field, as it is the longest

follow-up data for a multicenter CAR-T cell trial for those patients who

have failed to respond to other treatment options," said Stephan A.

Grupp, MD, PhD, Director of the Cancer Immunotherapy Program and Section

Chief of Cell Therapy and Transplant at Children's Hospital of

Philadelphia, and a Professor of Pediatrics in the Perelman School of

Medicine at the University of Pennsylvania. "Seeing that the majority of

responding patients from ELIANA are still in remission for this long

after a one-time infusion further establishes Kymriah as a truly

transformative treatment option."

The 19-month analysis from the JULIET study of Kymriah in adult patients

with r/r DLBCL showed prolonged durability of response in patients

(n=99) who had previously been through multiple rounds of chemotherapy

and unsuccessful stem cell transplants. The overall response rate (ORR)

after a median of 19 months of follow-up was 54% (95% CI, 43% - 64%; CR,

40%; partial response [PR], 13%) among patients who were followed for at

least 3 months or discontinued earlier. The mDOR was not reached at the

time of analysis indicating most responders were still experiencing a

response at the time of analysis; and the relapse-free probability,

which was 66% (95% CI, 51%-78%) at 6 months, remained consistent at 64%

(95% CI, 48%-76%) between 12-month and 18-month analyses. Further, 54%

(15/28) of patients who had achieved a PR converted to CR. Median OS for

all infused patients was 11.1 months (95% CI, 6.6 months-NE) and not

reached (95% CI, 21 months-NE) for patients in CR. The OS probability

was 48% (95% CI, 38%-57%) at 12 months and 43% (95%CI, 33%-53%) at 18

months (max follow-up, 29 months). Analyses of ORR, DOR and OS data

showed consistent results across all patient subgroups, regardless of

relapsed/refractory status, age and high-risk cytogenetics.

The safety profile observed in the 19-month follow-up from JULIET

continued to be consistent with previous reports and no deaths occurred

due to causes other than disease progression in this longer-term follow

up analysis. Within eight weeks of infusion with Kymriah, Grade 3/4 CRS,

as defined by the Penn Grading Scale, was reported in 23% of patients.

CRS management was conducted per the Penn CRS management algorithm,

which is specific to Kymriah. Tocilizumab and steroids were used in 16%

and 11% of patients, respectively, to treat CRS. Eleven percent of

patients had Grade 3/4 neurologic adverse events, which were managed

with supportive care[2].

The updated JULIET data will be presented today in a poster at the ASH

annual meeting (Abstract #1684; Saturday, December 1, 6:15 PM PST).

"Before CAR-T cell therapy, achieving and maintaining a prolonged

complete response in adult patients with relapsed or refractory DLBCL

was incredibly rare, but now we are seeing Kymriah result in durable

complete responses more than a year and a half after infusion[4]," said

lead author of the updated JULIET analysis, 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. "For physicians treating

this patient population, duration of response and a consistent safety

profile are incredibly important data points, and the findings from this

updated analysis further instill confidence in the continuing potential

of Kymriah in the treatment of these patients."

Kymriah is approved in the US, the EU, Canada and Switzerland for

children and young adults with relapsed or refractory ALL and in adult

patients with relapsed or refractory DLBCL, making it the only CAR-T

cell therapy approved for two distinct indications and delivering the

transformative potential for durable responses for patients who relapse

or don't respond to initial therapies and for whom the outlook is poor.

Patients do not need to be in complete remission to receive Kymriah and

no donor is required.

About the ELIANA Trial

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

trial, examining patients in 25 centers in 11 countries across the US,

Canada, Australia, Japan and the EU, including: Austria, Belgium, France,

Germany, Italy, Norway and Spain, demonstrating effective distribution

of Kymriah 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.

About the JULIET Trial

JULIET is the first multi-center global registration study for Kymriah

in adult patients with r/r DLBCL. JULIET, led by researchers at the

University of Pennsylvania, is the largest and only registration study

examining a CAR-T cell therapy in DLBCL, enrolling patients from 27

sites in 10 countries across the US, Canada, Australia, Japan and Europe,

including Austria, France, Germany, Italy, Norway and the Netherlands.

Kymriah(R) (tisagenlecleucel, formerly CTL019) US Important Safety

information

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 difficulty breathing, fever

(100.4degF/38degC or higher), 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,

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December 01, 2018 14:30 ET (19:30 GMT)