Press Release: Novartis JULIET trial of Kymriah demonstrates more than one-year durability of responses in adults with relapsed or refractory DLBCL

Novartis International AG / Novartis JULIET trial of Kymriah

demonstrates more than one-year durability of responses in adults with

relapsed or refractory DLBCL. Processed and transmitted by Nasdaq

Corporate Solutions. The issuer is solely responsible for the content of

this announcement.

-- Overall response rate was 52% and median duration of response was not

reached at a median follow-up of 14 months, signifying responses were

durable[1]

-- Patients had a 65% chance of being relapse-free one year after onset of

response[1]

-- With eight months of additional follow-up, response rates remained

consistent with previous reports and the safety profile was maintained

with no emergence of new safety signals

Basel, June 16, 2018 - Novartis today announced 14-month results from

the pivotal JULIET clinical trial showing ongoing durable responses are

achievable with Kymriah(R) (tisagenlecleucel) when administered to adult

patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma

(DLBCL). The overall response rate (ORR) was 52% (95% confidence

interval [CI], 41% - 62%), among 93 evaluable patients who were followed

for at least 3 months or discontinued earlier[1]. A complete response

(CR) was achieved in 40% of patients and 12% achieved a partial response

(PR). Of the patients in CR at month 3, 83% remained in CR at month 12,

and the median duration of response was not reached, indicating

sustainability of response. These data will be presented in an oral

presentation at the 23(rd) Annual Congress of the European Hematology

Association (EHA) (Abstract # S799; Saturday, June 16, 11:30AM CEST)[1].

"Advanced aggressive lymphoma patients who once faced a poor prognosis

now have the possibility of sustained remission after a single course of

therapy - a previously unimaginable and revolutionary breakthrough,"

said the lead author of the updated JULIET analysis Peter Borchmann, MD,

Department of Internal Medicine, University Hospital of Cologne,

Germany. "With 14 months of data from JULIET, we are seeing that Kymriah

may continue to redefine outcomes for patients with relapsed or

refractory DLBCL."

In the JULIET study, the relapse-free probability at 12 months after a

patient's first response (n=48) was 65% (95% CI, 49%-78%). In fact, 54%

(13/24) of patients who had achieved a PR converted to CR, including two

patients between months 9 and 12. Median overall survival (OS) was not

reached for patients in CR (95% CI, 17.9-NE). The OS rate at 12 months

was 49% and median OS was 11.7 months among all infused patients (n=111)

(95% CI, 6.6-NE). The median time from infusion to data cutoff was 14

months with a maximum time from infusion of 23 months. At the time of

data cutoff, no patients in response following treatment with Kymriah

proceeded to stem cell transplant[1].

"These results from JULIET continue to show Kymriah delivers strong

efficacy with durable responses, and a predictable and consistent safety

profile more than a year after infused in patients with advanced DLBCL,"

said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development.

"Novartis is committed to bringing this important and innovative

treatment option to more patients around the world."

Within eight weeks of infusion with Kymriah, Grade 3/4 cytokine release

syndrome (CRS), as defined by the Penn Grading Scale - a rigorous scale

for grading CRS -, was reported in 22% of patients (14% grade 3; 8%

grade 4). Fifteen percent of patients received tocilizumab for treatment

of CRS, including only 3% of patients with Grade 2 CRS and 50% of

patients with Grade 3 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. No deaths due to cerebral

edema were reported[1].

In this analysis, 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 32%, 20% and 15% of patients, respectively[1].

"When we continued follow-up with DLBCL patients in the global JULIET

study, we were extremely pleased that response rates were maintained a

year or more after infusion with Kymriah, which was consistent with the

durable responses seen in the pilot studies conducted at Penn," said

Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus

Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and

Research in Penn's Perelman School of Medicine and director of the

Lymphoma Program at the Abramson Cancer Center. "We look forward to

continuing to follow these patients who we hope will remain in remission

from their disease."

Analyses to better characterize and predict severe CRS and neurologic

events, including relationships with baseline clinical and laboratory

parameters, dose and cellular kinetics will also be presented.

Fifty patients discontinued before infusion and the majority did so due

to rapid progression of their disease or deterioration in their clinical

status reflecting the acute and progressive nature of r/r DLBCL. Twelve

out of 165 (7.3%) enrolled patients could not be infused due to

inability to manufacture an adequate dose of CAR-T cells.

In May 2018, the US Food and Drug Administration (FDA) approved Kymriah

for the treatment of adult patients with r/r large B-cell lymphoma after

two or more lines of systemic therapy including DLBCL, high grade B-cell

lymphoma and DLBCL arising from follicular lymphoma based on data from

the JULIET study. Kymriah is not approved for the treatment of patients

with primary central nervous system lymphoma. The European Medicines

Agency (EMA) is evaluating the Marketing Authorization Application (MAA)

for Kymriah for the treatment of children and young adults with r/r

B-cell acute lymphoblastic leukemia (ALL) and for adult patients with

r/r DLBCL.

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 globally conducted

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. 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 DLBCL

DLBCL is the most common form of non-Hodgkin lymphoma, a cancer of the

lymphatic system, accounting for up to 40% of all NHL cases globally[2].

An estimated 27,650 new cases of DLBCL were diagnosed in the US in

2016[3]. The crude incidence of DLBCL in Europe per year is 3.8 cases

per 100,000 people, and incidence increases with age and varies

considerably across Europe[4]. Roughly one-third of patients with DLBCL

relapse after receiving first-line treatment[4]. Out of those patients

diagnosed with DLBCL, about 10% have refractory disease and about 75% of

patients who relapse or are refractory to treatment are ineligible for

ASCT[2],[5]. For patients who relapse or don't respond to initial

therapy, there are limited treatment options that provide durable

responses and median life expectancy is approximately six months[6].

About Kymriah Manufacturing

Kymriah is manufactured for each individual patient using their own

cells at the Novartis Morris Plains, New Jersey facility. 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. Novartis has significant CAR-T manufacturing

experience and has demonstrated a reproducible product. Novartis has

manufactured CAR-T cells for more than 300 patients from 11 countries.

Novartis continues to advance its CAR-T manufacturing expertise in

Morris Plains.

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,

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

loss of balance. Patients should be advised to call their healthcare

provider or get emergency help right away if they experience any of

these signs and symptoms of CRS or neurological toxicities.

Because of the risk of CRS and neurological toxicities, Kymriah is only

available through a restricted program under a Risk Evaluation and

Mitigation Strategy (REMS) called Kymriah REMS.

Serious allergic reactions, including anaphylaxis, may occur after

Kymriah infusion. Kymriah can increase the risk of life-threatening

infections that may lead to death. Patients should be advised to tell

their healthcare provider right away if they develop fever, chills, or

any signs or symptoms of an infection.

Patients may experience prolonged low blood cell counts (cytopenia),

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June 16, 2018 05:30 ET (09:30 GMT)