Press Release: Novartis drug Tasigna(R) is approved by FDA as first and only CML therapy with Treatment-free Remission data in its label

Novartis International AG / Novartis drug Tasigna(R) is approved by FDA

as first and only CML therapy with Treatment-free Remission data in its

label. Processed and transmitted by Nasdaq Corporate Solutions. The

issuer is solely responsible for the content of this announcement.

-- Inclusion of Treatment-free Remission (TFR) data provides additional and

novel option in management of Ph+ CML-CP

-- Deep and sustained molecular response included as key eligibility

criteria for attempting TFR after treatment with Tasigna

-- Approval granted under priority review and is based on Novartis trials

evaluating TFR with Tasigna in both the first-line and second-line

settings

Basel, December 22, 2017 - Novartis announced today that the US Food and

Drug Administration (FDA) approved the inclusion of Treatment-free

Remission (TFR) data in the Tasigna(R) (nilotinib) US product label.

Tasigna is now the first and only BCR-ABL tyrosine kinase inhibitor

(TKI) to include data about attempting treatment discontinuation in

eligible adult patients with Philadelphia chromosome-positive chronic

myeloid leukemia in the chronic phase (Ph+ CML-CP) after achieving

sustained deep molecular response of MR4.5 (BCR-ABL1 International Scale

[IS] <= 0.0032%) in its FDA-approved prescribing information. TFR is the

ability to maintain a sustained molecular response* after stopping TKI

therapy in patients with Ph+ CML-CP. TFR requires scheduled monitoring

of BCR-ABL1 levels to identify possible loss of molecular response.

"It has long been our ambition at Novartis to make it possible for some

people with CML to discontinue therapy," said Bruno Strigini, CEO,

Novartis Oncology. "We are proud that Tasigna is now the first and only

TKI with TFR data in its labeling in the US and several countries around

the globe. This achievement would not have been possible without the

partnership of patients around the world who participated in our

groundbreaking TFR trials, helping Novartis to once again reimagine what

is possible for people living with CML."

With this label update, Tasigna is the only TKI that provides defined,

approved criteria to attempt and monitor TFR. This approval follows a

priority review for a supplemental New Drug Application (sNDA) for

Tasigna seeking the addition of TFR information and is based on safety

and efficacy results from the 96-week analyses of two open label trials,

ENESTfreedom and ENESTop. These trials evaluated the potential to

maintain MMR (BCR-ABL1 <= 0.1%) after stopping Tasigna therapy among

eligible adult patients with Ph+ CML-CP. Patients in the trials had

achieved a sustained MR4.5 with Tasigna in both the first-line setting

or after switching from Glivec(R) (imatinib)(**) [1]. The trials

demonstrated that almost half of the Ph+ CML-CP patients who

discontinued Tasigna remained in TFR approximately two years after

stopping treatment[1]. Among patients who did lose molecular response

during the TFR phase of the trials, nearly all regained MMR when Tasigna

therapy was promptly reinitiated[1]. The safety data are consistent with

previously published studies and the known safety profile of Tasigna[1].

The TFR data in the Tasigna label approved by the FDA included the use

of the MolecularMD MRDx(TM) BCR-ABL test, a FDA-authorized companion

diagnostic validated to measure BCR-ABL transcript levels down to

MR4.5[1]. Discontinuation of Tasigna should only be attempted under the

close supervision of a physician. Frequently scheduled patient

monitoring after Tasigna discontinuation is required so that possible

loss of MMR and MR4.0 (BCR-ABL1 IS <= 0.01%) is quickly identified and

treatment re-initiation is started promptly[1].

About Ph+ CML

CML is a type of cancer in which the body produces cancerous white blood

cells. Almost all patients with CML have an abnormality known as the

"Philadelphia chromosome," which produces a protein called BCR-ABL.

BCR-ABL causes malignant white blood cells to proliferate. Worldwide,

CML accounts for approximately 10% to 15% of all adult cases of leukemia,

with an incidence of one to two cases per 100,000 people per year.

About ENESTfreedom

ENESTfreedom (Evaluating Nilotinib Efficacy and Safety in Clinical

Trials - Following REsponsE in De nOvo CML-CP Patients) is an open label

Phase II study of 215 Ph+ CML-CP patients, conducted at 132 sites across

19 countries. The trial evaluated stopping treatment in 190 adults with

Ph+ CML-CP in patients who had achieved a response of MR4.5 with Tasigna

as a first-line treatment, who sustained deep molecular response for one

year prior to treatment discontinuation.

Results from the ENESTfreedom study found that 48.9% of 190 CML patients

(confidence interval [CI] 95%: 41.6%-56.3%) were able to discontinue

therapy and remain in MMR at 96 weeks[1]. Of the 88 patients who

promptly restarted treatment with Tasigna due to loss of MMR by the

cut-off date, 98.9% were able to regain MMR (n=87)[1]. One patient

discontinued the study at 7.1 weeks without regaining MMR after

reinitiating treatment with Tasigna[1]. Patients who discontinued

therapy were continually monitored for possible loss of molecular

response after treatment discontinuation. BCR-ABL transcript levels and

complete blood count with differential were monitored monthly for one

year, then every 6 weeks for the second year, and every 12 weeks

thereafter[1].

The safety data observed in this trial are consistent with the known

safety profile of Tasigna. AEs (all grades) in the predefined

musculoskeletal pain grouping decreased from 34.0% to 9.0% during the

first and second 48 weeks of the TFR phase, respectively, versus 17.0%

during the treatment consolidation phase[1].

About ENESTop

ENESTop (Evaluating Nilotinib Efficacy and Safety Trial) is an open

label Phase II study of 163 Ph+ CML-CP patients, conducted at 63 sites

across 18 countries. The trial evaluated stopping treatment in 126

adults with Ph+ CML-CP in patients who had been previously treated with

Glivec, and then switched to Tasigna, who achieved and sustained

molecular response for one year prior to treatment discontinuation.

ENESTop showed that more than half (53.2%) of patients were able to

remain in TFR at 96 weeks (95% CI: 44.1%-62.1%)[1]. In the study, 56

patients with confirmed loss of MR4.0 or loss of MMR restarted Tasigna

by the cut-off date[1]. Of these patients, 92.9% (n=52) regained both

MR4.0 and MR4.5[1]. Patients who discontinued therapy were continually

monitored for possible loss of molecular response after treatment

discontinuation. BCR-ABL transcript levels and complete blood count with

differential were monitored monthly for one year, then every 6 weeks for

the second year, and every 12 weeks thereafter[1].

The safety data observed in this trial are consistent with the known

safety profile of Tasigna. Rates of musculoskeletal pain-related AEs

(all grades) decreased from 47.9% to 15.1% during the first and second

48 weeks of the TFR phase, respectively, versus 13.7% during the

treatment consolidation phase[1].

Novartis Commitment to CML

Evaluating more than 1,000 patients, the Tasigna TFR clinical trial

program is among the most extensive in the industry. This large

international program designed to assess TKI discontinuation includes

ENESTfreedom and ENESTop, as well as two other ongoing company-sponsored

TFR studies and multiple investigator-initiated studies. Novartis'

commitment to innovation builds upon existing evidence to explore the

next advance for the care of people with CML.

Novartis' ongoing research in Ph+ CML has helped transform the disease

from a fatal leukemia to a chronic condition in most patients. The

company maintains an unwavering commitment to scientific innovation and

access to care for patients worldwide. As an organization committed to

patients, Novartis continues to reimagine CML by pursuing ambitious

goals with courage, passion and commitment for the global CML community.

About Tasigna

Tasigna (nilotinib) is approved in more than 122 countries for the

treatment of chronic phase and accelerated phase Philadelphia

chromosome-positive chronic myelogenous leukemia (Ph+ CML) in adult

patients resistant or intolerant to at least one prior therapy,

including Glivec (imatinib), and in more than 110 countries for the

treatment of adult patients with newly diagnosed Ph+ CML in chronic

phase. Tasigna is approved in the European Union (EU) for the treatment

of Ph+ CML in the chronic phase in pediatric patients with resistance or

intolerance to prior therapy including Glivec and for the treatment of

pediatric patients with newly diagnosed Ph+ CML in the chronic phase.

IMPORTANT SAFETY INFORMATION for TASIGNA(R) (nilotinib) Capsules

Use with caution in patients with uncontrolled or significant cardiac

disease and in patients who have or may develop prolongation of QTc. Low

levels of potassium or magnesium must be corrected prior to Tasigna

administration. Monitor closely for an effect on the QTc interval.

Baseline ECG is recommended prior to initiating therapy and as

clinically indicated. Cases of sudden death have been reported in

clinical studies in patients with significant risk factors. Avoid use of

concomitant drugs known to prolong the QT interval and strong CYP3A4

inhibitors. Avoid food 2 hours before and 1 hour after taking dose.

Reactivation of hepatitis B can occur in patients who are chronic

carriers of this virus after receiving TKI treatment.

Use with caution in patients with liver impairment, with a history of

pancreatitis and with total gastrectomy. Patients with rare hereditary

problems of galactose intolerance, severe lactase deficiency or

glucose-galactose malabsorption should not use Tasigna. Tasigna may

cause fetal harm in pregnant women. If pregnancy is planned during the

treatment-free remission phase, the patient must be informed of a

(MORE TO FOLLOW) Dow Jones Newswires

December 22, 2017 16:42 ET (21:42 GMT)