Novartis International AG /
Novartis receives positive CHMP opinion for first-line use of Zykadia in
ALK-positive advanced non-small cell lung cancer (NSCLC)
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* Phase III trial, first-line treatment with Zykadia resulted in improved
progression-free survival (PFS) over SOC chemotherapy with maintenance,
including in patients with brain metastases
* Zykadia is currently approved in the European Union (EU) for the treatment
of adult patients with ALK-positive advanced NSCLC previously treated with
Basel, May 19, 2017 - Novartis today announced the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency (EMA) has
recommended approval of expanding the use of Zykadia (ceritinib) to include the
first-line treatment of patients with advanced non-small cell lung cancer
(NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive. If approved,
Zykadia will provide a new treatment option for previously untreated and newly
diagnosed patients with ALK-positive advanced NSCLC.
"Novartis is committed to bringing targeted treatment options to more patients
living with lung cancer who may benefit from them," said Bruno Strigini, CEO,
Novartis Oncology. "Today, we've taken an important step towards fulfilling that
commitment with the potential approval of Zykadia as a first-line treatment
option for those in the EU diagnosed with ALK-positive advanced NSCLC."
The positive CHMP opinion was based on results from the ASCEND-4 study, a
randomized, open-label, global Phase III trial. The study showed that patients
treated with first-line Zykadia experienced a 45% reduction in the risk of
disease progression compared to patients treated with standard first-line
pemetrexed-platinum chemotherapy with pemetrexed maintenance (hazard ratio [HR]
= 0.55 [95% CI: 0.42, 0.73]). The median progression-free survival (PFS) was
16.6 months (95% confidence interval [CI]: 12.6, 27.2) for patients receiving
Zykadia compared to 8.1 months (95% CI: 5.8, 11.1) for patients in the
chemotherapy arm of the study.
Additionally, patients receiving Zykadia without brain metastases at baseline
experienced a median PFS of 26.3 months (95% CI: 15.4, 27.7), compared with 8.3
months (95% CI: 6.0, 13.7) among patients treated in the chemotherapy arm (HR =
0.48 [95% CI: 0.33, 0.69]). Among patients with brain metastases at baseline,
the median PFS was 10.7 months (95% CI: 8.1, 16.4) in the Zykadia group versus
6.7 months (95% CI: 4.1, 10.6) in the chemotherapy group (HR = 0.70 [95% CI:
0.44, 1.12]). Of these patients, 59% did not receive prior brain
radiotherapy. The high intracranial overall response rate (ORR) (72.7% [95%
CI: 49.8, 89.3]) was consistent with whole body ORR (72.5% [95% CI:
The CHMP recommendation will now be reviewed by the European Commission (EC),
which holds the authority to approve medicines for the European Union (EU). The
EC typically follows the CHMP recommendation and typically issues an approval
decision within two months, applicable to all 28 European Union member states
plus Iceland, Lichtenstein, and Norway. Earlier this year, the US Food and Drug
Administration (FDA) granted Zykadia Breakthrough Therapy designation for first-
line treatment of patients with ALK-positive NSCLC with metastases to the brain.
The application for first-line use of Zykadia is under Priority Review by the
Novartis Commitment to Lung Cancer
Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer
combined, and an estimated 1.8 million new cases of lung cancer are diagnosed
each year,. Among patients with NSCLC, roughly 25% have an actionable
mutation that may be targeted with available therapies-. To determine
that treatment, medical organizations recommend biomarker testing for patients
with lung cancer.
Over the past decade, Novartis Oncology's research has supported the evolution
of treatment approaches for patients living with mutation-driven types of lung
cancer. The company continues its commitment to the global lung cancer community
through ongoing studies, as well as the exploration of investigational compounds
that target genomic biomarkers in NSCLC.
ASCEND-4 was a Phase III randomized, open-label, multicenter, global clinical
trial to evaluate the safety and efficacy of Zykadia compared to standard
chemotherapy, including maintenance, in adult patients with Stage IIIB or IV
ALK-positive advanced NSCLC who received no prior therapy for their advanced
disease. Patients received Zykadia orally at 750 mg/daily or standard
pemetrexed-based platinum doublet chemotherapy (pemetrexed 500 mg/m2 plus
cisplatin 75 mg/m2 or carboplatin AUC 5-6) for four cycles followed by
Of 376 patients, 189 (59 with brain metastases) were randomized to Zykadia and
187 (62 with brain metastases) to chemotherapy. Approximately 60% of patients
with baseline brain metastases treated with Zykadia did not have prior radiation
therapy, the current standard of treatment for baseline brain metastases.
The most common adverse events (AEs) occurring in more than 25% of Zykadia
patients were diarrhea (85% vs. 11% with chemotherapy), nausea (69% vs. 55% with
chemotherapy), vomiting (66% vs. 36% with chemotherapy), ALT increase (60% vs.
22% with chemotherapy), AST increase (53% vs. 19% with chemotherapy), GGT
increase (37% vs. 10% in chemotherapy), decreased appetite (34% vs. 31% with
chemotherapy), blood alkaline phosphate increase (29% vs. 5% with chemotherapy)
and fatigue (29% vs. 30% with chemotherapy).
Zykadia is an oral, selective inhibitor of anaplastic lymphoma kinase (ALK), a
gene that can fuse with others to form an abnormal "fusion protein" that
promotes the development and growth of certain tumors in cancers including non-
small cell lung cancer (NSCLC). Zykadia is currently approved in over 69
countries worldwide. Please visit www.NovartisOncology.com/news/product-
portfolio/zykadia for additional information.
Zykadia Important Safety Information
Zykadia may cause serious side effects.
Zykadia may cause stomach upset and intestinal problems in most patients,
including diarrhea, nausea, vomiting and stomach-area pain. These problems can
be severe. Patients should follow their doctor's instructions about taking
medicines to help these symptoms, and should call their doctor for advice if
symptoms are severe or do not go away.
Zykadia may cause severe liver injury. Patients should have blood tests prior to
the start of treatment with Zykadia, every two weeks for the first three months
of treatment and monthly thereafter, and should talk to their doctor right away
if they experience any of the following symptoms: tiredness (fatigue), itchy
skin, yellowing of the skin or the whites of the eyes, nausea or vomiting,
decreased appetite, pain on the right side of the abdomen, urine turns dark or
brown, or bleeding or bruising more easily than normal.
Zykadia may cause severe or life-threatening swelling (inflammation) of the
lungs during treatment that can lead to death. Symptoms may be similar to those
symptoms from lung cancer. Patients should tell their doctor right away about
any new or worsening symptoms, including trouble breathing or shortness of
breath, fever, cough, with or without mucous, or chest pain.
Zykadia may cause very slow, very fast, or abnormal heartbeats. Doctors should
check their patient's heart during treatment with Zykadia. Patients should tell
their doctor right away if they feel new chest pain or discomfort, dizziness or
lightheadedness, faint, or have abnormal heartbeats, blue discoloration of lips,
shortness of breath, swelling of lower limbs or skin, or if they start to take
or have any changes in heart or blood pressure medicines.
Zykadia may cause high levels of glucose in the blood. People who have diabetes
or glucose intolerance, or who take a corticosteroid medicine have an increased
risk of high blood sugar with Zykadia. Patients should have glucose blood tests
prior to the start of treatment with Zykadia and during treatment. Patients
should follow their doctor's instructions about blood sugar monitoring and call
their doctor right away with any symptoms of high blood sugar, including
increased thirst and/or urinating often.
Zykadia may cause high levels of pancreatic enzymes in the blood and may cause
pancreatitis. Patients should have blood tests prior to the start of treatment
with Zykadia and as needed during their treatment with Zykadia. Patients should
talk to their doctor if they experience signs and symptoms of pancreatitis which
including upper abdominal pain that may spread to the back and get worse with
Before patients take Zykadia, they should tell their doctor about all medical
conditions, including liver problems; diabetes or high blood sugar; heart
problems, including a condition called long QT syndrome; if they are pregnant,
if they think they may be pregnant, or if they plan to become pregnant; are
breastfeeding or plan to breastfeed.
Zykadia may harm unborn babies. Women who are able to become pregnant must use a
highly effective method of birth control (contraception) during treatment with
Zykadia and up to 3 months after stopping Zykadia. It is not known if Zykadia
passes into breast milk. Patients and their doctor should decide whether to take
Zykadia or breastfeed, but should not do both.
Patients should tell their doctor about medicines they take, including
prescription medicines, over-the-counter medicines, vitamins and herbal
supplements. If they take Zykadia while using oral contraceptives, the oral
contraceptives may become ineffective.
The most common adverse reactions with an incidence of >=10% were diarrhea,
nausea, vomiting, liver laboratory test abnormalities (requires blood test
monitoring), tiredness (fatigue), abdominal pain, decreased appetite, weight
decreased, constipation, kidney laboratory test abnormalities (requires blood
test monitoring), rash, anemia and heartburn. Grade 3-4 adverse reactions with
an incidence of >=5% were liver laboratory test abnormalities, tiredness
(fatigue), vomiting, hyperglycemia (requires blood test monitoring), nausea and
Patients should stop taking Zykadia and seek medical help immediately if they
experience any of the following, which may be signs of an allergic reaction:
* Difficulty in breathing or swallowing
* Swelling of the face, lips, tongue or throat
* Severe itching of the skin, with a red rash or raised bumps
Patients should tell their doctor of any side effect that bothers them or does
not go away. These are not all of the possible side effects of Zykadia. For more
information, patients should ask their doctor or pharmacist.
Patients should take Zykadia exactly as their health care provider tells them.
Patients should not change their dose or stop taking Zykadia unless their health
care provider advises them to. Zykadia should be taken once a day on an empty
stomach. Patients should not eat for at least 2 hours before and 1 hour after
taking Zykadia. If a dose of Zykadia is missed, they should take it as soon as
they remember. If their next dose is due within the next 12 hours, they should
skip the missed dose and take the next dose at their regular time. They should
not take a double dose to make up for a forgotten dose. Patients should not
drink grapefruit juice or eat grapefruit during treatment with Zykadia, as it
may make the amount of Zykadia in their blood increase to a harmful level. If
patients have to vomit after swallowing Zykadia capsules, they should not take
more capsules until their next scheduled dose.
The foregoing release contains forward-looking statements that can be identified
by words such as "positive CHMP opinion," "recommended," "will," "committed,"
"may," "step towards," "commitment," "potential," "recommendation,"
"Breakthrough Therapy designation," "Priority Review," "ongoing,"
"investigational," or similar terms, or by express or implied discussions
regarding potential new indications or labeling for Zykadia, or regarding
potential future revenues from Zykadia. You should not place undue reliance on
these statements. Such forward-looking statements are based on the current
beliefs and expectations of management regarding future events, and are subject
to significant known and unknown risks and uncertainties. Should one or more of
these risks or uncertainties materialize, or should underlying assumptions prove
incorrect, actual results may vary materially from those set forth in the
forward-looking statements. There can be no guarantee that Zykadia will be
submitted or approved for any additional indications or labeling in any market,
or at any particular time. Nor can there be any guarantee that Zykadia will be
commercially successful in the future. In particular, management's expectations
regarding Zykadia could be affected by, among other things, the uncertainties
inherent in research and development, including clinical trial results and
additional analysis of existing clinical data; regulatory actions or delays or
government regulation generally; the company's ability to obtain or maintain
proprietary intellectual property protection; general economic and industry
conditions; global trends toward health care cost containment, including ongoing
pricing and reimbursement pressures; safety, quality or manufacturing issues,
and other risks and factors referred to in Novartis AG's current Form 20-F on
file with the US Securities and Exchange Commission. Novartis is providing the
information in this press release as of this date and does not undertake any
obligation to update any forward-looking statements contained in this press
release as a result of new information, future events or otherwise.
Novartis provides innovative healthcare solutions that address the evolving
needs of patients and societies. Headquartered in Basel, Switzerland, Novartis
offers a diversified portfolio to best meet these needs: innovative medicines,
cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has
leading positions globally in each of these areas. In 2016, the Group achieved
net sales of USD 48.5 billion, while R&D throughout the Group amounted to
approximately USD 9.0 billion. Novartis Group companies employ approximately
118,000 full-time-equivalent associates. Novartis products are sold in
approximately 155 countries around the world. For more information, please visit
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