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
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
-- 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.
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.
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.
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
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
(MORE TO FOLLOW) Dow Jones Newswires
June 14, 2019 02:30 ET (06:30 GMT)