-
In ALK-positive metastatic
NSCLC patients, Zykadia median progression-free survival (PFS) was
16.6 months, compared to 8.1 months with chemotherapy[1]
-
The overall intracranial
response rate in patients with measurable brain metastases was 57%
for patients treated with Zykadia, compared to 22% for patients
treated with chemotherapy[1]
-
Approval provides a new
treatment option for previously untreated patients
Basel, May 26, 2017 - Novartis today announced the US Food and Drug
Administration (FDA) approved the expanded use of
Zykadia® (ceritinib)
to include the first-line treatment of patients with metastatic
non-small cell lung cancer (NSCLC) whose tumors are anaplastic
lymphoma kinase (ALK)-positive, as detected by an FDA-approved
test. Zykadia first received accelerated approval in 2014 for
patients with ALK-positive metastatic NSCLC who progressed on or
are intolerant to crizotinib. In January 2017, the FDA granted
Zykadia Breakthrough Therapy designation for the first-line
treatment of patients with ALK-positive metastatic NSCLC with
metastases to the brain, and Priority Review for first-line
ALK-positive metastatic NSCLC.
The first-line approval of Zykadia is based on
results from an open-label, randomized, multicenter, global, Phase
III trial, ASCEND-4. The study demonstrated that patients treated
with first-line Zykadia had a median progression-free survival
(PFS) of 16.6 months (95% confidence interval [CI]: 12.6, 27.2),
compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated
with standard first-line pemetrexed-platinum chemotherapy with
pemetrexed maintenance[1].
Overall intracranial response rate (OIRR) in
patients with measurable brain metastases was 57% (95% CI: 37, 76;
n = 28) for patients treated with Zykadia, versus 22% (95% CI: 9,
42; n = 27) for patients treated with chemotherapy[1]. The whole
body overall response rate (ORR) was 73% (95% CI: 66, 79; n = 187)
in patients treated with Zykadia[1].
"Today's approval represents the next step in the
development of Zykadia as a treatment option for ALK-positive
metastatic NSCLC, bringing this important medication to a patient
population where a need still exists," said Bruno Strigini, CEO,
Novartis Oncology. "At Novartis, we are tireless in our pursuit of
developing novel medicines to treat lung cancer, and the first-line
approval of Zykadia for ALK-positive metastatic NSCLC illustrates
our commitment to cancer patients."
Approximately 3-7% of all patients with NSCLC have
an ALK gene rearrangement[2]. An FDA-approved test at the time of
diagnosis may help to determine the presence of this mutation and,
thus, the most appropriate treatment option[3].
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[4],[5]. Among patients with
NSCLC, roughly 25% have an actionable mutation that may be targeted
with available therapies[6].
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.
About ASCEND-4
ASCEND-4 is 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 pemetrexed maintenance.
Of 376 patients, 189 (59 with brain metastases)
were randomized to Zykadia and 187 (62 with brain metastases) to
chemotherapy[1]. Approximately 70% of patients with measurable
brain metastases at baseline did not have prior radiation therapy,
the current standard of treatment for baseline brain metastases[1].
Among patients randomized to the chemotherapy arm, 43% received
Zykadia as their next treatment after platinum-based
chemotherapy[1].
Patients treated with first-line Zykadia had a
median PFS of 16.6 months (95% CI: 12.6, 27.2), compared to 8.1
months (95% CI: 5.8, 11.1) for patients treated with standard
first-line pemetrexed-platinum chemotherapy with pemetrexed
maintenance[1]. A 45% risk reduction in PFS was obtained in the
Zykadia arm compared to the chemotherapy arm (hazard ratio [HR] =
0.55 [95% CI: 0.42, 0.73; one-sided p value <0.0001])[1].
Patients without brain metastases at screening
receiving Zykadia 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 with chemotherapy (HR = 0.48 [95% CI: 0.33,
0.69])[7]. Among patients with brain metastases at screening, 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])[7].
The most common adverse reactions in ASCEND-4
(incidence >=25% all grades) were diarrhea (85%), nausea (69%),
vomiting (67%), fatigue (45%), abdominal pain (40%), decreased
appetite (34%) and cough (25%)[1]. In ASCEND-4, Grade 3/4
adverse reactions (incidence >=2%) were fatigue (7%),
vomiting (5%), diarrhea (4.8%), abdominal pain (3.7%), weight loss
(3.7%), nausea (2.6%) and prolonged QT interval (2.6%)[1]. The most
common laboratory abnormalities in ASCEND-4 (incidence >=25% all
grades) were increased ALT/AST (91%/86%), increased GGT (84%),
increased alkaline phosphatase (81%), creatinine increase (77%),
anemia (67%), hyperglycemia (53%), decreased phosphate (38%),
increased amylase (37%) and neutropenia (27%)[1]. In ASCEND-4,
Grade 3/4 laboratory abnormalities (incidence >=2%) were
increased GGT (49%), ALT/AST (34%/21%), increased alkaline
phosphatase (12%), hyperglycemia (10%), increased amylase (8%),
increase lipase (6%), creatinine increase (4.2%), anemia (4.2%),
decreased phosphate (3.7%) and neutropenia (2.1%)[1].
About Zykadia
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
https://www.hcp.novartis.com/products/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 month 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 eating.
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. 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.
The most common adverse reactions with an
incidence of >=10% diarrhea, nausea, vomiting, liver laboratory
test abnormalities, fatigue, abdominal pain, decreased appetite,
weight decreased constipation, blood creatinine increased, rash,
anemia, and esophageal disorder.
Grade 3-4 adverse reactions with an
incidence of >=5% were fatigue, vomiting, diarrhea, abdominal
pain, weight loss, nausea, and prolonged QT Interval.
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.
Please see full Prescribing
Information for Zykadia.
Disclaimer
The foregoing release contains forward-looking statements that can
be identified by words such as "Breakthrough Therapy designation,"
"next step," "tireless," "commitment," "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.
About Novartis
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
http://www.novartis.com.
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References
[1] Zykadia® (ceritinib) Full Prescribing
Information.
[2] Lovly, C., L. Horn, W. Pao. 2016. Molecular Profiling of Lung
Cancer. My Cancer Genome.
https://www.mycancergenome.org/content/disease/lung-cancer/.
(Updated March 28). Accessed March 22, 2017.
[3] Lindeman, N.I., et al. Molecular Testing Guideline for
Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase
Inhibitors. Arch Pathol Lab Med. 2013; 137:
828-1174.
[4] World Health Organization. International Agency for Research on
Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and
Prevalence Worldwide in 2012. Lung Cancer. Available at
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx?cancer=lung.
Accessed March 22, 2017.
[5] Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Cancer
Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012;
10: 226-224.
[6] Korpanty, G.J., et al. Biomarkers that currently affect
clinical practice in lung cancer: EGFR, ALK, MET, ROS-1, and KRAS.
Frontiers in Oncology. 2014; 4: 204.
[7] Soria JC, et al. First-line ceritinib versus platinum-based
chemotherapy in advanced ALK-rearranged non-small-cell lung cancer
(ASCEND-4): A randomized, open-label Phase 3 study. The Lancet. 2017; 389(10072):917-929.
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