Novartis receives FDA approval for expanded use of Zykadia® in first-line ALK-positive metastatic non-small cell lung cancer (NSCLC)
(Thomson Reuters ONE) -
Novartis International AG /
Novartis receives FDA approval for expanded use of Zykadia® in first-line
ALK-positive metastatic non-small cell lung cancer (NSCLC)
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The issuer is solely responsible for the content of this announcement.
* 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.
Novartis is on Twitter. Sign up to follow (at)Novartis at
http://twitter.com/novartis and (at)NovartisCancer at
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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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Source: Novartis International AG via GlobeNewswire
Unternehmensinformation / Kurzprofil:
Datum: 26.05.2017 - 21:31 Uhr
Sprache: Deutsch
News-ID 544845
Anzahl Zeichen: 20164
contact information:
Town:
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Kategorie:
Business News
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