Novartis drug Afinitor® significantly improves progression-free survival in advanced nonfunctional gastrointestinal and lung NET
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Novartis International AG /
Novartis drug Afinitor® significantly improves progression-free survival in
advanced nonfunctional gastrointestinal and lung NET
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* In pivotal study, everolimus reduced risk of disease progression by 52%;
showed 11.0-month median progression-free survival vs 3.9 months for
placebo[1]
* Advanced, progressive, nonfunctional neuroendocrine tumors of GI or lung
origin are rare forms of cancer with poor prognoses and limited treatment
options[2],[3,[4]
* RADIANT-4 results highlighted at key European cancer congress; worldwide
regulatory filings are underway[1]
Basel, September 27, 2015 - Novartis announced today results of a Phase III
pivotal study showing Afinitor(®) (everolimus) tablets reduced the risk of
progression by 52% (hazard ratio [HR] = 0.48; 95% confidence interval [CI],
0.35-0.67; p<0.00001) vs placebo in patients with advanced, progressive,
nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung
origin. The study, RADIANT-4, will be presented at the European Cancer Congress
(ECC) 2015 in Vienna, Austria, and was highlighted in the ECC press conference
on Saturday, September 26[1].
Additionally, the data show everolimus, a mammalian target of rapamycin (mTOR)
inhibitor, extended median progression free survival (PFS) by 7.1 months: median
PFS by central review was 11.0 months (95% CI, 9.23-13.3) in the everolimus arm
and 3.9 months (95% CI, 3.58-7.43) in the placebo arm. Overall survival (OS) was
a key secondary endpoint of the trial. While the OS data are not mature, the
first interim analysis showed a trend favoring the everolimus arm. Additional OS
analyses are planned. Another secondary endpoint was best overall response rate;
the study found that 64% of patients receiving everolimus experienced at least
some degree of tumor shrinkage compared to 26% of those on placebo[1].
Safety was also a secondary endpoint of the trial and adverse events (AEs) were
consistent with the known safety profile of everolimus. The most common
treatment-related grade 3/4 AEs (>5%) for everolimus and placebo, respectively,
were stomatitis (9.0% vs 0.0%), diarrhea (7.0% vs 2.0%) and infections (7.0% vs
0.0%)[1].
"Advanced, progressive, nonfunctional NET of GI or lung origin are rare and
aggressive cancers, with limited treatment options," said James Yao, MD,
Professor of Medicine, The University of Texas MD Anderson Cancer Center,
Houston, Texas, and the study's principal investigator. "These pivotal trial
results demonstrate strong evidence for the efficacy of the mTOR inhibitor
everolimus in this patient population."
NET are a rare type of cancer that originate in neuroendocrine cells found
throughout the body, and are most often found in the GI tract, lungs or
pancreas[5]. NET can be functional or nonfunctional: functional NET produce
symptoms caused by the secretion of hormones and other substances; nonfunctional
NET may produce symptoms caused by the tumor's growth, such as intestinal
blockage, pain and bleeding[5],[6],[7],[8]. At time of diagnosis, 5%-44% of
patients with NET in the GI system and 28% of patients with lung NET have
advanced disease, meaning the cancer has spread to other parts of the body and
is more difficult to treat[5].
"These results show that everolimus has the potential to be a new, clinically
meaningful therapy for patients with advanced, progressive, nonfunctional GI or
lung NET, which typically have poor prognoses," said Alessandro Riva, MD, Global
Head, Novartis Oncology Development and Medical Affairs. "Our work with the
RADIANT clinical program demonstrates our long-term commitment to NET and has
yielded important data that have led to improved outcomes for patients with
different types of NET."
The results of the RADIANT-4 study-part of the largest clinical trial program in
patients with advanced NET-will serve as the basis of worldwide regulatory
submissions for Afinitor for the treatment of advanced, progressive,
nonfunctional GI and lung NET. Afinitor is already approved in more than 95
countries worldwide for locally advanced, metastatic or unresectable progressive
NET of pancreatic origin.
About RADIANT-4
RADIANT-4 (RAD001 In Advanced Neuroendocrine Tumors) is a Phase III prospective,
double-blind, randomized, parallel group, placebo-controlled, multicenter study.
The trial examined the efficacy and safety of everolimus plus best supportive
care (BSC) vs placebo plus BSC in 302 patients with progressive, well-
differentiated, nonfunctional, advanced NET of GI or lung origin. All patients
received BSC during treatment, which excluded antitumor agents such as
somatostatin analogues (SSAs). Patients were required to have ceased treatment
with SSAs for 4 weeks before study entry. Everolimus demonstrated similar
efficacy regardless of whether the patient had prior SSA therapy or not.
Patients had no history or active symptoms of carcinoid syndrome, and had
documented disease progression within the previous 6 months. Patients were
randomized 2:1 to receive either daily everolimus 10 mg or daily placebo
orally[1].
The primary endpoint of RADIANT-4 was PFS by central radiology review. Secondary
endpoints included safety, OS, best overall response rate (defined as complete
response plus partial response) and disease control rate[1].
The safety profile of everolimus was consistent with what has been observed in
previous studies of this drug. The most common treatment-related AEs included
stomatitis, diarrhea, peripheral edema, fatigue, and rash. At the time of the
data analysis cutoff date, the primary reasons for treatment discontinuation
were disease progression (37% in the everolimus arm vs 72% in the placebo arm)
and adverse events (29% in the everolimus arm vs 7% in the placebo arm). A trend
towards improved survival was observed at the time of interim OS analysis
[HR=0.64; 95% CI, 0.40-1.05; p=0.037], with a total of 70 deaths recorded at the
time of the data cutoff (42 [20.5%] in the everolimus arm and 28 [28.6%] in the
placebo arm). The result was not statistically significant, since interim
analysis significance threshold was p=0.000213[1].
About Afinitor(®) (everolimus) tablets
Afinitor(® )(everolimus) is approved in more than 95 countries, including the
United States and throughout the European Union, for locally advanced,
metastatic or unresectable progressive neuroendocrine tumors of pancreatic
origin. It is also approved in 121 countries including the United States and
European Union for advanced renal cell carcinoma following progression on or
after vascular endothelial growth factor (VEGF)-targeted therapy.
Afinitor is also approved in more than 100 countries including the United States
and European Union for advanced HR+/HER2- breast cancer in combination with
exemestane, after prior endocrine therapy.
Everolimus is also available from Novartis for use in certain non-oncology
patient populations under the brand names Afinitor(®) or Votubia(®), Certican(®)
and Zortress(®) and is exclusively licensed to Abbott and sublicensed to Boston
Scientific for use in drug-eluting stents.
Indications vary by country and not all indications are available in every
country. The safety and efficacy profile of everolimus has not yet been
established outside the approved indications. Because of the uncertainty of
clinical trials, there is no guarantee that everolimus will become commercially
available for additional indications anywhere else in the world.
Important Safety Information about Afinitor(®) (everolimus) tablets
Afinitor/Votubia can cause serious side effects including lung or breathing
problems, infections (including sepsis), and kidney failure, which can lead to
death. Patients taking concomitant angiotensin-converting enzyme (ACE)
inhibitors may be at an increased risk for angioedema. Mouth ulcers and mouth
sores are common side effects. Afinitor/Votubia can affect blood cell counts,
kidney and liver function, and blood sugar, cholesterol, and triglyceride
levels. Afinitor/Votubia may cause fetal harm in pregnant women. Highly
effective contraception is recommended for women of child-bearing potential
while receiving Afinitor/Votubia and for up to eight weeks after ending
treatment. Women taking Afinitor/Votubia should not breast feed. Fertility in
women and men may be affected by treatment with Afinitor/Votubia.
The most common adverse drug reactions (incidence >=10 percent) are mouth
ulcers, skin rash, feeling tired or weak, diarrhea, infections (including upper
respiratory tract infection, sore throat and runny nose, sinusitis, middle ear
infection and pneumonia), absence of menstrual periods, high levels of
cholesterol, nausea, decreased appetite, low level of red blood cells, acne,
abnormal taste, irregular menstrual periods, inflammation of lung tissue,
swelling of extremities or other parts of the body, high level of blood sugar,
itching, weight loss, nose bleeds, cough and headache. The most common grade
3-4 adverse drug reactions (incidence >=2 percent) are mouth ulcers, infections
(including pneumonia), low level of red blood cells, absence of menstrual
periods, high level of blood sugar, feeling tired or weak, diarrhea, low white
blood cells, inflammation of lung tissue and spontaneous bleeding or bruising.
Cases of hepatitis B reactivation, blood clots in the lung or legs, and
pneumocystis jirovecii pneumonia (PJP) have been reported. Abnormalities were
observed in hematology and clinical chemistry laboratory tests.
Disclaimer
The foregoing release contains forward-looking statements that can be identified
by words such as "underway," "will," "planned," "potential," "commitment,"
"yet," or similar terms, or by express or implied discussions regarding
potential new indications or labeling for everolimus, or regarding potential
future revenues from everolimus. 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 everolimus 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 everolimus will
be commercially successful in the future. In particular, management's
expectations regarding everolimus could be affected by, among other things, the
uncertainties inherent in research and development, including unexpected
clinical trial results and additional analysis of existing clinical data;
unexpected 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 pressures; unexpected
safety issues; unexpected manufacturing or quality 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,
eye care and cost-saving generic pharmaceuticals. Novartis is the only global
company with leading positions in these areas. In 2014, the Group achieved net
sales of USD 58.0 billion, while R&D throughout the Group amounted to
approximately USD 9.9 billion (USD 9.6 billion excluding impairment and
amortization charges). Novartis Group companies employ approximately 120,000
full-time-equivalent associates. Novartis products are available in more than
180 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.
References
[1] Yao J, et al. Everolimus in advanced, nonfunctional neuroendocrine tumors of
lung or gastrointestinal origin: Efficacy and safety results from the placebo-
controlled, double-blind, multicenter, Phase 3 RADIANT-4 study. European Cancer
Congress (ECC) 2015, Vienna, Austria.
[2] American Cancer Society. Gastrointestinal Carcinoid Tumors. Available at
http://www.cancer.org/acs/groups/cid/documents/webcontent/003102-pdf.pdf.
Accessed September 2015.
[3] American Cancer Society. Lung Carcinoid Tumors. Available at
http://www.cancer.org/acs/groups/cid/documents/webcontent/003117-pdf.pdf.
Accessed September 2015.
[4] Halfdanarson T.R., et al. Pancreatic neuroendocrine tumors (PNETs):
incidence, prognosis and recent trend toward improved survival. Annals of Onc.
2008; 19: 1727-1733.
[5] Yao J, et al. One hundred years after "Carcinoid:" Epidemiology of and
prognostic factors for neuroendocrine tumors in 35,825 cases in the United
States. J Clin Oncol. 2008; 26: 3063-72.
[6] Akerstrom G, et al. Timing and extent of surgery in symptomatic and
asymptomatic neuroendocrine tumors of the pancreas in MEN 1. Langenbecks Arch
Surg. 2002; 386:558-69.
[7] Modlin I, et al. Priorities for improving the management of
gasteroenteropancreatic neuroendocrine tumors. J Natl Cancer Inst.
2008;100: 1282-1289.
[8] Modlin I, et al. Current status of gastrointestinal carcinoids.
Gastroenterology. 2005;128 :1717-1751.
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Datum: 27.09.2015 - 00:23 Uhr
Sprache: Deutsch
News-ID 422822
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