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14.06.2019 08:29:52

Press Release: Novartis continues to innovate in CML with long-term treatment-free remission results following Tasigna(R) use and promising combination data ...

Novartis International AG / Novartis continues to innovate in CML with

long-term treatment-free remission results following Tasigna(R) use and

promising combination data with investigational compound asciminib

(ABL001). Processed and transmitted by West Corporation. The issuer is

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solely responsible for the content of this announcement.

-- Results from two Phase II trials, ENESTfreedom and ENESTop, support and

extend previous findings of long-term durability of molecular response

after stopping Tasigna, reducing time on drug for many CML patients1,2

-- New Phase I data for asciminib in combination with imatinib, nilotinib or

dasatinib in heavily pre-treated Ph+ CML-CP patients demonstrate

potential molecular response and a well-tolerated safety profile3,4

Basel, June 14, 2019 - Long-term follow-up data from the ongoing,

pivotal open-label ENESTfreedom and ENESTop trials showed sustained

treatment-free remission (TFR) after stopping frontline and second-line

Tasigna (nilotinib) therapy in eligible adult patients with Philadelphia

chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic

phase (CP). Separate data demonstrate promising results for asciminib

(ABL001), an investigational allosteric BCR-ABL inhibitor, in

combination with three different tyrosine kinase inhibitors (TKIs) in

heavily pre-treated Ph+ CML-CP patients. The results will be presented

at the 24(th) Congress of the European Hematology Association (EHA) in


"We are pleased to report many of our Tasigna clinical-trial patients

continue to maintain treatment-free remission for nearly four years with

a low adverse event burden," said John Tsai, MD, Head of Global Drug

Development and Chief Medical Officer, Novartis. "Long-term trials like

ENESTfreedom and ENESTop, as well as promising Phase I data from

asciminib, are helping us to reimagine medicine and the way CML is


Results from the ENESTfreedom study showed that about 44% of patients

remained in TFR (84/190) for 192 weeks after stopping frontline Tasigna

treatment. The treatment-free survival rate at 192 weeks was nearly 49%.

About 99% (90/91) and 92% (84/91) of patients who resumed nilotinib due

to loss of major molecular response (MMR) during the TFR phase regained

MMR and molecular response(4.5), respectively. Among 91 patients who

resumed nilotinib, the most common adverse events (AEs) were

nasopharyngitis (18.7%) as well as pruritus, fatigue and increased

lipase (14.3% each). The majority of AEs were grade 1/2(1).

Consistent results were observed in the ENESTop trial: About 46% of

patients remained in TFR (58/126) for 192 weeks after stopping

second-line Tasigna treatment. The treatment-free survival rate at 192

weeks was over 50%. Among 59 patients who resumed nilotinib, the most

common AEs were hypertension (20.3%) and arthralgia (13.6%). The

majority of AEs were grade 1/2(2).

Novartis will also present data from a Phase I trial of asciminib in

combination with ATP-competitive TKI in heavily-pretreated patients with

Ph+ CML-CP. Importantly, each combination was evaluated in a dose

finding study assessing different asciminib dose levels, so results are

not comparable across the three treatment arms. The preliminary results


Among patients who at baseline did not achieve BCR-ABL1 International

Scale [IS] <1%, by 48 weeks(3,4) :

-- 60% (9/15) achieved molecular response <1% in the asciminib-plus-imatinib

arm, and

-- 43% (6/14) and 56% (5/9) patients achieved molecular response <1% in the

asciminib-plus-nilotinib and asciminib-plus-dasatinib arms, respectively.

In evaluable patients without MMR at baseline, by 48 weeks(3,4) :

-- 42% (8/19) achieved MMR with asciminib plus imatinib with median

treatment exposure of 54.6 weeks, and

-- 31% (4/13) patients with asciminib plus nilotinib and 36% (5/14) patients

with asciminib plus dasatinib, respectively, achieved MMR.

No patients with MMR at baseline lost MMR due to either of the three

combination therapies. All combinations showed tolerable safety profile

in heavily pretreated CML patients(3,4) :

-- Among patients who received asciminib plus imatinib, the most common

any-grade AEs were nausea (32%), increased lipase (20%), as well as

abdominal pain, peripheral edema and vomiting (16% each).

-- Among patients who received asciminib plus nilotinib, most common

any-grade AEs were myalgia (35%), increased lipase (29%), and increased

amylase, fatigue and pruritus (24% each).

-- Among patients who received asciminib plus dasatinib, most common

any-grade AEs were increased lipase (35%) and diarrhea, headache and

nausea (18% each).

"While the introduction of TKIs has changed the CML treatment paradigm,

there remains a subset of patients who are intolerant or resistant to

TKI therapy," said Jorge Cortes, MD, Deputy Chair and Professor of

Medicine in the Department of Leukemia at MD Anderson Cancer Center,

Houston Texas. "These initial results from combination therapy with

currently available TKIs and a BCR-ABL1 inhibitor like asciminib are

encouraging - and give us the potential to increase molecular response

and prevent development of mutations."

Commitment to CML

Our ongoing research in Ph+ CML has helped transform the disease from a

fatal leukemia to a chronic condition in most patients. Novartis

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 care by pursuing ambitious goals

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

About Tasigna

Tasigna (nilotinib) is approved in more than 130 countries for the

treatment of adult patients with newly diagnosed Philadelphia

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

phase and with chronic and accelerated phase Ph+ CML resistant or

intolerant to at least one prior therapy, including Glivec(R)

(imatinib). Tasigna is also approved for the treatment of pediatric

patients with newly diagnosed Ph+ CML in the chronic phase and with

resistance or intolerance to prior TKI therapy.

About asciminib

Asciminib (ABL001) is an investigational allosteric BCR-ABL inhibitor

with a mechanism of action distinct from currently available TKI

treatments for patients with CML. There is a broad clinical development

program underway for asciminib both as a potential monotherapy such as

the Phase III ASCEMBL third-line CML study and in combination with other

therapies, such as the Phase II ASC4MORE study investigating asciminib

plus imatinib for patients with CML-CP without deep molecular response.

It is currently being studied in patients with and without genetic

mutations that make them resistant to many targeted CML therapies. If

proven safe and effective, asciminib has the potential to be a

meaningful therapy, increasing the treatment options in CML and

addressing the treatment needs of patients.


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

potential need to re-initiate treatment with Tasigna during pregnancy.

Women should not breastfeed while taking Tasigna and for 2 weeks after

the last dose.

Cases of cardiovascular events included ischemic heart disease-related

events, peripheral arterial occlusive disease, and ischemic

cerebrovascular events have been reported. Serious cases of hemorrhage

from various sites including gastrointestinal were reported in patients

receiving Tasigna. Grade 3 or 4 fluid retention including pleural

effusion, pericardial effusion, ascites and pulmonary edema have been

reported. Cases of tumor lysis syndrome have been reported in

Tasigna-treated patients who were resistant or intolerant to prior CML


In pediatric patients the long-term effects of prolonged treatment with

Tasigna is unknown.

Eligible patients who are confirmed to express the typical BCR-ABL

transcripts, e13a2/b2a2 or e14a2/b3a2, can be considered for treatment

discontinuation. Frequent monitoring of BCR-ABL transcript levels in

patients eligible for treatment discontinuation must be performed with a

quantitative diagnostic test validated to measure molecular response

levels with a sensitivity of at least MR(4.5) (BCR-ABL/ABL <=0.0032%

IS). BCR-ABL transcript levels must be assessed prior to and during

treatment discontinuation. Loss of major molecular response

(MMR=BCR-ABL/ABL <=0.1% IS) or confirmed loss of MR(4) (two consecutive

measures separated by at least 4 weeks showing loss of MR(4) (MR(4)

=BCR-ABL/ABL <=0.01% IS) will trigger treatment re-initiation within 4

weeks of when loss of remission is known to have occurred. It is crucial

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June 14, 2019 02:30 ET (06:30 GMT)