Press Release: Kymriah(R) (tisagenlecleucel), first-in-class CAR-T therapy from Novartis, receives second FDA approval to treat appropriate r/r patients with...

Novartis International AG / Kymriah(R) (tisagenlecleucel),

first-in-class CAR-T therapy from Novartis, receives second FDA approval

to treat appropriate r/r patients with large B-cell lymphoma. Processed

and transmitted by Nasdaq Corporate Solutions. The issuer is solely

responsible for the content of this announcement.

-- Kymriah demonstrated an overall response rate of 50%, with median

duration of response not yet reached at the time of data cut-off,

indicating sustainability of response[1]

-- Kymriah is the only CAR-T therapy FDA-approved for two distinct

indications - in non-Hodgkin lymphoma (NHL) and B-cell acute

lymphoblastic leukemia (ALL)

-- Novartis has established leadership based on first-to-launch CAR-T

therapy experience, existing treatment center network and payor

environment understanding, which helps to support access and anticipated

patient demand

-- Novartis continues to collaborate with the Centers for Medicare and

Medicaid Services (CMS) on various value-based pricing initiatives

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

https://novartis.gcs-web.com/Kymriah-tisagenlecleucel-first-in-class-CAR-T-therapy-from-Novartis-receives-second-FDA-approval-to-treat-appropriate-r-r-patients-with-large-B-cell-lymphoma

Basel, May 1, 2018 - Novartis today announced the US Food and Drug

Administration (FDA) has approved Kymriah(R) (tisagenlecleucel)

suspension for intravenous infusion for its second indication - the

treatment of adult patients with relapsed or refractory (r/r) large

B-cell lymphoma after two or more lines of systemic therapy including

diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma and

DLBCL arising from follicular lymphoma. Kymriah is not indicated for the

treatment of patients with primary central nervous system lymphoma.

Kymriah, developed in collaboration with the University of Pennsylvania,

became the first chimeric antigen receptor T cell (CAR-T) therapy to

receive regulatory approval in August 2017 for the treatment of patients

up to 25 years of age with B-cell precursor acute lymphoblastic leukemia

(ALL) that is refractory or in second or later relapse. Kymriah is now

the only CAR-T cell therapy to receive FDA approval for two distinct

indications in non-Hodgkin lymphoma (NHL) and B-cell ALL.

"Today's FDA approval of Kymriah provides another opportunity for

Novartis to build on its leadership in CAR-T development, delivering a

potentially transformative therapy with durable and sustained response

rates and a well-characterized safety profile to help patients in dire

need of new treatment options," said Liz Barrett, CEO, Novartis

Oncology. "We look forward to leveraging all of our learnings and new

capabilities from the initial launch of Kymriah in pediatric and young

adult B-cell ALL for this larger group of patients."

DLBCL is the most common form of NHL[2],[3]. 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[4],[5].

"The goal of Kymriah is to provide physicians with a therapy that has

demonstrated durable response rates in relapsed or refractory DLBCL

patients, a patient population that has endured multiple rounds of

chemotherapy with many having experienced unsuccessful stem cell

transplants," 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. "With

this approval, physicians now have a meaningful therapeutic option that

can achieve and maintain a sustained response without stem cell

transplant along with a consistent safety profile."

Kymriah is an innovative immunocellular therapy that is a one-time

treatment manufactured individually for each patient using the patient's

own T cells. Kymriah uses the 4-1BB costimulatory domain in its chimeric

antigen receptor to enhance cellular expansion and persistence. 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.

As part of the Novartis commitment to ensure eligible patients have

access to Kymriah, the company continues to collaborate with the Centers

for Medicare and Medicaid Services (CMS) on the creation of an

appropriate value-based pricing approach. Novartis continues to be an

innovator and leader in value and innovative-based pricing options, and

is proud to work with CMS and other stakeholders across the healthcare

spectrum on creating a sustainable and modern healthcare payment system.

To ensure all hospitals and their associated clinics are aware of how to

manage the risks of cytokine release syndrome (CRS) and neurological

toxicities, Kymriah is available through a Risk Evaluation and

Mitigation Strategy (REMS) program. The REMS program serves to inform

and educate healthcare professionals about the risks that may be

associated with Kymriah treatment. To support safe patient access,

Novartis has established a network of certified treatment centers

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

and appropriate patient care, and there are currently treatment centers

which are certified and fully operational to begin treatment of eligible

patients with DLBCL.

To address the unique aspects of this therapy, Novartis offers various

patient programs and resources to support safe and timely access for

patients and address a range of needs.

Novartis is also committed to bringing Kymriah to patients outside the

US. In January 2018, Novartis announced that the European Medicines

Agency (EMA) granted accelerated assessment to the Marketing

Authorization Application (MAA) for Kymriah for the treatment of

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

with r/r DLBCL who are ineligible for ASCT. Accelerated assessment is

granted to therapies which may provide a significant improvement in the

safety and effectiveness of the treatment of a serious disease, and the

designation is intended to expedite the standard review time. Novartis

plans additional regulatory submissions for Kymriah in pediatric and

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

DLBCL beyond the US and EU in 2018.

About Kymriah JULIET Pivotal Study

The FDA approval of Kymriah in adult patients with r/r DLBCL is based on

the pivotal phase II JULIET clinical trial, the first multi-center

global registration study for Kymriah in adult patients with r/r DLBCL.

JULIET was conducted in collaboration with Penn, and is the largest

study examining a CAR-T 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 the JULIET trial, patients were infused in the inpatient and

outpatient setting.

In this Novartis-sponsored study, Kymriah showed an overall response

rate (ORR) of 50% (95% confidence interval [CI], 38% - 62%), with 32% of

patients achieving a complete response (CR) and 18% achieving a partial

response (PR) in 68 patients evaluated for efficacy. The median duration

of response was not reached among these patients, indicating

sustainability of response[1].

In all patients infused with Kymriah (n=106), severe or life-threatening

(grade 3/4) CRS, defined by the Penn Grading Scale -a rigorous scale for

grading this reaction-, occurred in 23% of patients. 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.

Eighteen percent of all infused patients experienced grade 3/4

neurologic events, which were managed with supportive care.

Encephalopathy, a distinctive neurotoxicity associated with CAR-T

therapies, was seen as severe or life-threatening in 11% of patients.

There were no deaths attributed to neurological events, and no fatal

cases of cerebral edema have occurred. Grade 3/4 cytopenias lasting more

than 28 days included thrombocytopenia (40%) and neutropenia (25%), and

grade 3/4 infections occurred in 25%. The most common (>20%) adverse

events (AEs) in the JULIET study are CRS, infections, pyrexia, diarrhea,

nausea, fatigue, hypotension, edema and headache[1].

About Kymriah Manufacturing

Kymriah is 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 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. 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 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.

Novartis has also successfully established the Kymriah manufacturing

process at the Fraunhofer-Institut for cell therapy and immunology

(Fraunhofer-Institut für Zelltherapie and Immunologie) facility in

Leipzig, Germany, which currently supports the manufacturing of Kymriah

(MORE TO FOLLOW) Dow Jones Newswires

May 01, 2018 16:26 ET (20:26 GMT)