Novartis drug Votubia® recommended by CHMP for approval in the EU for children and adults with SEGA associated with tuberous sclerosis
0
Novartis International AG /
Novartis drug Votubia® recommended by CHMP for approval in the EU for children
and adults with SEGA associated with tuberous sclerosis
. Processed and transmitted by Thomson Reuters ONE.
The issuer is solely responsible for the content of this announcement.
* If approved, Votubia (everolimus) will be first medication in EU for
subependymal giant cell astrocytoma (SEGA) associated with tuberous
sclerosis complex (TSC)
* CHMP opinion based on Phase II study of 28 patients showing 33% experienced
a SEGA tumor reduction of 50% or greater at six months relative to
baseline[1]
* Brain surgery is only treatment option in EU for growing SEGAs, benign brain
tumors that primarily affect children and adolescents[1], [2], [3], [4]
* Worldwide regulatory submissions for everolimus to treat this patient
population are under way; first approval received in the US in 2010 as
Afinitor(®)
Basel, June 24, 2011 - The Committee for Medicinal Products for Human Use (CHMP)
of the European Medicines Agency (EMA) adopted a positive opinion for Votubia(®
)(everolimus) tablets* for the treatment of patients aged 3 years and older with
subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis
complex (TSC), who require therapeutic intervention but are not amenable to
surgery. If approved, Votubia will be the first medication available for these
patients in the European Union (EU).
Tuberous sclerosis complex, also known as tuberous sclerosis (TS), may cause
benign tumors to form in vital organs and can affect many different parts of the
body, most commonly the brain[5], [6]. Signs of TSC vary depending on which
system and which organs are involved[5]. SEGAs, or benign brain tumors, occur in
up to 20% of patients with TSC[1]. Tuberous sclerosis complex is also associated
with a variety of resulting disorders including seizures, swelling in the brain
(hydrocephalus), developmental delays and skin lesions[1], [2], [5]. Currently,
brain surgery is the only treatment option for patients in the EU with growing
SEGAs associated with TSC[1].
The CHMP positive opinion is for a conditional approval based on a prospective,
open-label, single-arm, Phase II study of 28 patients. Results showed that 78%
of patients (21 of 27) experienced a reduction of 30% or greater in the size of
their largest SEGA and 33% (9 of 27) experienced a reduction of 50% or greater
at six months relative to baseline[1].
"The positive CHMP opinion for Votubia is encouraging as it may lead to the
approval of the first medication in the European Union for patients with this
challenging disease, " said Hervé Hoppenot, President of Novartis Oncology. "Our
focus on tuberous sclerosis complex research reflects the commitment Novartis
has made to develop innovative therapies to help address unmet medical needs."
The European Commission generally follows the recommendations of the CHMP and
delivers its final decision within three months of the CHMP recommendation. The
decision will be applicable to all 27 EU member states plus Iceland and Norway.
Regulatory approvals have already been granted for SEGA associated with TSC in
the United States, Switzerland, Brazil, Colombia, Guatemala, the Philippines and
South Korea. Additional submissions to global regulatory agencies are under way
worldwide.
Everolimus targets mTOR, a protein that acts as an important regulator of tumor
cell division, blood vessel growth and cell metabolism[8]. Tuberous sclerosis
complex is caused by defects in the TSC1 and/or TSC2 genes[5]. When these genes
are defective, mTOR activity is increased, which can cause uncontrolled tumor
cell growth and proliferation, blood vessel growth and altered cellular
metabolism, leading to the formation of benign tumors throughout the body,
including the brain[1]. By inhibiting mTOR activity in this protein pathway,
everolimus may reduce cell proliferation, blood vessel growth and glucose uptake
related to SEGA associated with TSC[1].
Tuberous sclerosis complex is a genetic disorder affecting approximately one to
two million people worldwide[5]. In Europe, the prevalence in the general
population is estimated to be nearly nine cases per 100,000[7].
About the Phase II Study
This prospective, open-label, single-arm study was conducted in 28 patients aged
three years and above (median age=11, range 3-34) with evidence of serial SEGA
growth[1].
In the study, 78% of patients (21 of 27) experienced a reduction of 30% or
greater in the size of their largest SEGA and 33% (9 of 27) experienced a
reduction of 50% or greater at six months relative to baseline. This evidence is
based on an analysis of change in SEGA volume. No patient developed a new SEGA,
had worsening hydrocephalus or required surgery or other therapy for SEGA while
receiving everolimus[1].
The most common adverse reactions reported (incidence >=10%) in the prospective,
open-label, single-arm trial were infections, increased aspartate transaminase
(AST), mouth sores, increased cholesterol, decreased white blood cell count,
increased alanine transaminase (ALT), increased triglycerides, decreased
hemoglobin, fever, decreased glucose, acneiform dermatitis, increased glucose,
diarrhea, decreased platelet counts, acne, cough and increased creatinine. The
only grade 3 adverse reactions were infections (single cases of sinusitis,
pneumonia, tooth infection and viral bronchitis), and single cases of mouth
sores, elevated AST concentrations and decreased neutrophil count. No grade 4
adverse reactions were reported. However, the reliability of the frequency of
adverse reactions and laboratory abnormalities reported in this trial is limited
because of the small number of patients.
All data from the Phase II study submitted to the EMA are based on the cut-off
date of December 9, 2009.
About everolimus
Votubia(®) (everolimus) tablets is approved in Switzerland for the treatment of
patients 3 years of age and older, with SEGA associated with TS, for whom
surgery is not a suitable option. Should everolimus be approved in the EU, the
trade name will be Votubia. In the US, Afinitor(®) (everolimus) tablets is
approved to treat patients with SEGA associated with TS who require therapeutic
intervention but are not candidates for curative surgical resection. The
effectiveness of everolimus is based on an analysis of change in SEGA volume.
Clinical benefit such as improvement in disease-related symptoms or increase in
overall survival has not been shown.
Afinitor is approved in the US for the treatment of progressive neuroendocrine
tumors of pancreatic origin in patients with unresectable, locally advanced or
metastatic disease. The FDA determined that the safety and effectiveness of
Afinitor in the treatment of patients with carcinoid tumors have not been
established. Novartis has submitted a marketing application for everolimus to
the European Medicines Agency (EMA) for this use, and additional regulatory
submissions are under way worldwide.
Afinitor is approved in the EU for the treatment of patients with advanced renal
cell carcinoma (RCC) whose disease has progressed on or after treatment with
vascular endothelial growth factor (VEGF)-targeted therapy and also in the US
for the treatment of patients with advanced RCC after failure of treatment with
sunitinib or sorafenib.
In the EU, everolimus is available in different dosage strengths for the non-
oncology patient population under the trade name Certican(®) for the prevention
of organ rejection in heart and kidney transplant recipients. In the US,
everolimus is available in different dosage strengths under the trade name
Zortress(®) for the prophylaxis of organ rejection in adult patients at low-
moderate immunologic risk receiving a kidney transplant.
Everolimus is exclusively licensed to Abbott and sublicensed to Boston
Scientific for use in drug-eluting stents.
Not all indications are available in every country. 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 Votubia/Afinitor
Votubia can cause serious side effects including lung or breathing problems,
infections, and renal failure which can lead to death. Mouth ulcers and mouth
sores are common side effects. Votubia can affect blood cell counts, kidney and
liver function, blood sugar and cholesterol levels. Votubia may cause fetal harm
in pregnant women. Women taking Votubia should not breast feed.
The most common adverse drug reactions (incidence >=15%) are mouth ulcers, rash,
diarrhea, fatigue, acneiform dermatitis, infections, weakness, nausea,
peripheral swelling, decreased appetite, headache, pneumonitis, abnormal taste,
nose bleeds, mucosal inflammation, weight decreased and vomiting. The most
common grade 3-4 adverse drug reactions (incidence >=2%) are mouth ulcers,
fatigue, decreased white blood cell count, diarrhea, infections, pneumonitis and
diabetes mellitus. Cases of hepatitis B reactivation and pulmonary embolism have
been reported.
Disclaimer
The foregoing release contains forward-looking statements that can be identified
by terminology such as "recommended, " "will, " "may, " "commitment, "
"recommendations, " "under way, " or similar expressions, 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 reflect the
current views of management regarding future events, and involve known and
unknown risks, uncertainties and other factors that may cause actual results
with everolimus to be materially different from any future results, performance
or achievements expressed or implied by such 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 achieve any particular levels of revenue
in the future. In particular, management´s expectations regarding everolimus
could be affected by, among other things, unexpected regulatory actions or
delays or government regulation generally; unexpected clinical trial results,
including unexpected new clinical data and unexpected additional analysis of
existing clinical data; the company´s ability to obtain or maintain patent or
other proprietary intellectual property protection; competition in general;
government, industry and general public pricing pressures; the impact that the
foregoing factors could have on the values attributed to the Novartis Group´s
assets and liabilities as recorded in the Group´s consolidated balance sheet,
and other risks and factors referred to in Novartis AG´s current Form 20-F on
file with the US Securities and Exchange Commission. Should one or more of these
risks or uncertainties materialize, or should underlying assumptions prove
incorrect, actual results may vary materially from those anticipated, believed,
estimated or expected. 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 healthcare solutions that address the evolving needs of
patients and societies. Focused solely on healthcare, Novartis offers a
diversified portfolio to best meet these needs: innovative medicines, eye care,
cost-saving generic pharmaceuticals, consumer health products, preventive
vaccines and diagnostic tools. Novartis is the only company with leading
positions in these areas. In 2010, the Group´s continuing operations achieved
net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1
billion excluding impairment and amortization charges) was invested in R&D
throughout the Group. Headquartered in Basel, Switzerland, Novartis Group
companies employ approximately 119,000 full-time-equivalent associates and
operate in more than 140 countries around the world. For more information,
please visithttp://www.novartis.com.
Novartis is on Twitter. Sign up to follow @Novartis at
http://twitter.com/novartis.
*Known as Afinitor(®) (everolimus) tablets for this patient population in some
countries. If approved in the EU for this patient population, the trade name
will be Votubia.
References
[1] Krueger, et al. Everolimus for Subependymal Giant-Cell Astrocytomas in
Tuberous Sclerosis. New Eng J Med 2010;363:1801-11.
[2] Adriaensen ME, et al. Prevalence of subependymal giant cell tumors in
patients with tuberous sclerosis and a review of the literature. Eur J Neurol
2009;16:691-6.
[3] Nabbout R, et al. Early diagnosis of subependymal giant cell astrocytoma in
children with tuberous sclerosis. J Neurol Neurosurg Psychiatry 1999;66:370-375.
[4] Medkour A, et al. Neonatal Subependymal Giant Cell Astrocytoma. Pediatr
Neurosurg 2002;36:271-274.
[5] National Institute of Neurological Disorders and Stroke. Tuberous Sclerosis
Fact Sheet. Available
athttp://www.ninds.nih.gov/disorders/tuberous_sclerosis/detail_tuberous_sclerosi
s.htm. Accessed June 2011.
[6] Inoki, et al. Tuberous sclerosis complex, implication from a rare genetic
disease to common cancer treatment. Human Molecular Genetics 2009;18(1):R94-
R100.
[7] Orphanet Report Series."Prevalence of rare diseases: Bibliographic Data."
Available
athttp://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_a
lphabetical_list.pdf. Accessed June 2011.
[8] Motzer, et. al. Phase 3 Trial of Everolimus for Metastatic Renal Cell
Carcinoma. Cancer 2010 Sep;116(18):4256-4265.
# # #
Novartis Media Relations
Central media line : +41 61 324 2200
Eric Althoff Nicole Riley
Novartis Global Media Relations Novartis Oncology
+41 61 324 7999 (direct) +1 862 778 3110
+41 79 593 4202 (mobile) nicole.riley@novartis.com
eric.althoff@novartis.com
e-mail: media.relations@novartis.com
Novartis Investor Relations
Central phone: |+41 61 324 7944 | |
----------------------+-----------------+---------------+---------------------
Susanne Schaffert |+41 61 324 7944 |North America: |
----------------------+-----------------+---------------+---------------------
Pierre-Michel Bringer|+41 61 324 1065 |Richard Jarvis |+1 212 830 2433
----------------------+-----------------+---------------+---------------------
Thomas Hungerbuehler |+41 61 324 8425 |Jill Pozarek |+1 212 830 2445
----------------------+-----------------+---------------+---------------------
Isabella Zinck |+41 61 324 7188 |Edwin Valeriano|+1 212 830 2456
----------------------+-----------------+---------------+---------------------
| | |
----------------------+-----------------+---------------+---------------------
|
----------------------------------------+-------------------------------------
e-mail: investor.relations@novartis.com|e-mail:
|investor.relations@novartis.com
--- End of Message ---
Novartis International AG
Postfach Basel
WKN: 904278;ISIN: CH0012005267;
Media release (PDF):
http://hugin.info/134323/R/1525934/461718.pdf
This announcement is distributed by Thomson Reuters on behalf of
Thomson Reuters clients. The owner of this announcement warrants that:
(i) the releases contained herein are protected by copyright and
other applicable laws; and
(ii) they are solely responsible for the content, accuracy and
originality of the information contained therein.
Source: Novartis International AG via Thomson Reuters ONE
[HUG#1525934]
CH0012005267
