Novartis drug Votubia® recommended by CHMP for EU approval to treat refractory partial-onset seizures in patients with TSC
(Thomson Reuters ONE) -
Novartis International AG /
Novartis drug Votubia® recommended by CHMP for EU approval to treat refractory
partial-onset seizures in patients with TSC
. Processed and transmitted by Nasdaq Corporate Solutions.
The issuer is solely responsible for the content of this announcement.
* If approved, Votubia would be the first adjunctive treatment specifically
for refractory seizures in children and adults with tuberous sclerosis
complex (TSC)[1]
* Seizures are the most common TSC-related neurological manifestation, and
about 60% of patients become unresponsive to available anti-epileptic
therapies[2]
* CHMP positive opinion based on pivotal study showing adjunctive treatment
with everolimus achieved clinically significant seizure reduction in
patients with TSC[1]
Basel, December 16, 2016 - Novartis today announced that the Committee for
Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA)
adopted a positive opinion for Votubia(®) (everolimus) dispersible tablets* as
an adjunctive treatment of patients aged two years and older whose refractory
partial-onset seizures, with or without secondary generalization, are associated
with tuberous sclerosis complex (TSC). If approved by the European Commission
(EC), Votubia would address an unmet need as currently there are no
pharmacologic treatments approved specifically for the treatment of refractory
seizures associated with TSC[1].
"As refractory seizures are among the most debilitating manifestations of TSC, a
new therapy that provides seizure control would be a meaningful advance for
these patients in the EU," said Bruno Strigini, CEO, Novartis Oncology. "This
CHMP opinion is an important milestone in our longstanding commitment to
improving care for patients affected by TSC."
The positive CHMP opinion was based on efficacy and safety data from a pivotal
Phase III study (EXIST-3: EXamining everolimus In a Study of TSC), which found
that when used as an adjunctive therapy, everolimus significantly reduced
refractory partial-onset seizures associated with TSC compared to placebo. The
youngest patient enrolled was two years of age and patients in all treatment
arms received one to three anti-epileptic drugs (AEDs). Seizure response rate
(>=50% reduction) was significantly greater with everolimus low exposure (LE)
(28.2%, 95% CI 20.3 - 37.3; p=0.008) and high exposure (HE) (40.0%, 95% CI 31.5
- 49.0; p<0.001) vs placebo (15.1%, 95% CI 9.2 - 22.8). The median percentage
reduction from baseline in seizure frequency was also significantly greater
among patients randomized to everolimus LE (29.3%, 95% CI 18.8 - 41.9; p=0.003)
and HE (39.6%, 95% CI 35.0 - 48.7; p<0.001) vs placebo (14.9%, 95% CI 0.1 -
21.7). The most common all-grade adverse events (AEs) of any cause reported
during the core phase at frequencies >15% in everolimus LE/HE arms included
stomatitis, diarrhea, pyrexia, nasopharyngitis, and upper respiratory tract
infection[1].
The EC typically adheres to the recommendation of the CHMP and usually delivers
its final decision in two months or earlier. The decision will be applicable to
all 28 European Union (EU) member states plus Iceland and Norway. In Europe,
everolimus has orphan drug designation for TSC. Orphan drugs are those that
treat a condition which affects no more than five in 10,000 people in the EU[3].
Tuberous sclerosis complex is a rare genetic disorder affecting up to one
million people worldwide[4]. Approximately 85% of individuals with TSC are
affected by epilepsy, and uncontrolled seizures associated with TSC can be
debilitating for patients[2]. Everolimus is the only approved non-surgical
option indicated for treating non-cancerous brain and kidney tumors in certain
patients with TSC. EXIST-3 is the first Phase III study to demonstrate the
significant benefit of adjunctive everolimus in the treatment of refractory
partial-onset seizures in patients with TSC[1],[5],[6]. These data may be used
to support regulatory filings in other countries.
Everolimus works by inhibiting the mammalian target of rapamycin (mTOR), a
protein that regulates multiple cellular functions. TSC is caused by mutations
in the TSC1 or TSC2 genes, resulting in hyperactive signaling of the mTOR
pathway which can lead to increased cellular growth and proliferation, neuronal
hyper-excitability, abnormalities in cortical architecture and network function
and impaired synaptic plasticity[7],[8]. Pre-clinical research suggests that
hyperactive mTOR activity may influence several mechanisms of epileptogenesis,
the gradual process by which the brain develops epilepsy in TSC[9].
About EXIST-3 (EXIST-3: EXamining everolimus In a Study of TSC)
EXIST-3 is a Phase III, three-arm, randomized, double-blind, placebo-controlled
study of the efficacy and safety of high and low exposure ranges of everolimus
as adjunctive therapy in patients with TSC who have refractory partial-onset
seizures, defined as seizures persisting despite the use of two anti-epileptic
drugs (AEDs). The study enrolled male and female participants (ages 2.2-56.3
years) with clinically defined TSC, who were on stable doses of one to three
AEDs for at least four weeks prior to a two-month, pre-randomization, evaluation
period[1].
The primary objective was to assess the effectiveness of adjunctive everolimus
as compared to placebo in reducing refractory partial-onset seizures in patients
with TSC who are taking one to three AEDs. Secondary objectives included the
percentage of patients free from seizure during the maintenance period, change
in seizure frequency, and safety.
The most frequent (>=10%) all grade adverse events (AEs), of any cause, reported
with everolimus LE/HE vs placebo included stomatitis (55.0%/64.0% vs 9.0%),
diarrhea (17.1%/21.5% vs 5.0%), nasopharyngitis (13.7%/16.2% vs 16.0%), upper
respiratory tract infection (12.8%/15.4% vs 12.6%), pyrexia (fever) (19.7%/13.8%
vs 5.0%), vomiting (12.0%/10.0% vs 9.2%), cough (11.1%/10.0% vs 3.4%) and rash
(6.0%/10.0% vs 2.5%). Grade 3 or 4 AEs occurred in 13 (11.0%) patients in the
placebo group, 21 (18.0%) in the LE group, and 31 (24.0%) in the HE group[1].
About tuberous sclerosis complex
Tuberous sclerosis complex (TSC) may cause non-cancerous tumors to form in vital
organs including the brain, kidney, heart, lungs, and skin, as well as resulting
disorders such as epilepsy, autism, cognitive impairment, behavioral problems,
and psychiatric disorders. Many people with TSC show evidence of the disease in
the first year of life. However, because manifestations vary from person to
person and can take years to develop, many children are not diagnosed until
later in life, often with the onset of seizures, skin lesions or other
significant symptoms, such as developmental delays. Because TSC is a lifelong
condition, the latest professional diagnostic guidelines issued in 2012 advise
that individuals be monitored by a doctor experienced with the disorder to
ensure tumor growth or new symptoms are identified early[7],[10].
About Votubia® (everolimus)
In the European Union (EU), everolimus is approved as Votubia(®) tablets for the
treatment of adult patients with renal angiomyolipoma associated with tuberous
sclerosis complex (TSC) who are at risk of complications (based on factors such
as tumor size or presence of aneurysm, or presence of multiple or bilateral
tumors) but who do not require immediate surgery. The evidence is based on
analysis in sum of angiomyolipoma volume. Votubia(®) tablets and dispersible
tablets are also indicated in the EU for the treatment of patients with
subependymal giant cell astrocytoma (SEGA) associated with TSC who require
therapeutic intervention but are not amenable to surgery. The evidence is based
on analysis of change in SEGA volume. Further clinical benefit, such as
improvement in disease-related symptoms, has not been demonstrated.
In the United States (US), everolimus is approved as Afinitor(®) tablets for the
treatment of adult patients with renal angiomyolipoma and TSC, not requiring
immediate surgery. Afinitor(®) tablets and Afinitor Disperz(TM) (dispersible
tablets) are also indicated in the US in pediatric and adult patients with TSC
for the treatment of SEGA that requires therapeutic intervention but cannot be
curatively resected.
Additionally, Afinitor tablets is approved in >110 countries, including the US
and throughout the EU, for locally advanced, metastatic or unresectable
progressive neuroendocrine tumors (NET) of pancreatic origin and in the US and
EU for the treatment of adult patients with progressive, well-differentiated
(Grade 1 or 2), nonfunctional NET of gastrointestinal (GI) or lung origin that
are unresectable, locally advanced or metastatic. It is also approved in >120
countries including the US and EU for advanced renal cell carcinoma following
progression on or after vascular endothelial growth factor (VEGF)-targeted
therapy (in the US, specifically following sunitinib and sorafenib). Afinitor is
also approved in 115 countries including the US and EU for advanced HR+/HER2-
breast cancer in combination with exemestane, after prior endocrine therapy.
Everolimus is also available from Novartis under the brand names Afinitor(®),
Certican(®) and Zortress(®) for use in oncology and transplant patient
populations 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
Votubia/Afinitor 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. Votubia/Afinitor can affect blood cell counts,
kidney and liver function, and blood sugar, cholesterol, and triglyceride
levels. Votubia/Afinitor may cause fetal harm in pregnant women. Highly
effective contraception is recommended for women of child-bearing potential
while receiving Votubia/Afinitor and for up to eight weeks after ending
treatment. Women taking Votubia/Afinitor should not breast feed. Fertility in
women and men may be affected by treatment with Votubia/Afinitor.
The most common adverse drug reactions (incidence >=10 percent) are infections
(including sore throat and runny nose, upper respiratory tract infection,
pneumonia, sinusitis, and urinary tract infection), mouth ulcers, skin rash,
feeling tired, diarrhea, fever, vomiting, nausea, cough, decreased appetite, low
level of red blood cells, headache, abnormal taste, absence of menstrual
periods, acne, inflammation of lung tissue, irregular menstrual periods,
swelling of extremities or other parts of the body, high level of blood sugar,
feeling weak, itching, weight loss, high levels of cholesterol, and nose
bleeds. The most common Grade 3-4 adverse drug reactions (incidence >=2
percent) are mouth ulcers, infections (including pneumonia), low level of red
blood cells, high level of blood sugar, feeling tired, absence of menstrual
periods, diarrhea, low white blood cells, inflammation of lung tissue, feeling
weak, fever, 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 "recommended," "would," "positive opinion," "CHMP opinion,"
"commitment," "recommendation," "will," "may," "suggests," "yet," or similar
terms, or by express or implied discussions regarding potential new indications
or labeling for Votubia, or regarding potential future revenues from Votubia.
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 Votubia 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 Votubia will be commercially successful in the
future. In particular, management's expectations regarding Votubia 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, 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,
eye care and cost-saving generic pharmaceuticals. Novartis is the only global
company with leading positions in these areas. In 2015, the Group achieved net
sales of USD 49.4 billion, while R&D throughout the Group amounted to
approximately USD 8.9 billion (USD 8.7 billion excluding impairment and
amortization charges). Novartis Group companies employ approximately 118,000
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 and (at)NovartisCancer at
http://twitter.com/novartiscancer
For Novartis multimedia content, please visit www.novartis.com/news/media-
library
For questions about the site or required registration, please contact
media.relations(at)novartis.com
*Known as Afinitor® (everolimus) tablets for certain patients with SEGA and
renal angiomyolipoma associated with TSC in the US and other countries.
References
[1] French. J.A., et al. Adjunctive everolimus therapy for treatment-resistant
focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3,
randomised, double-blind, placebo-controlled study. Lancet. Available at
http://dx.doi.org/10.1016/S0140-6736(16)31419-2. Accessed December 2016.
[2] Chu-Shore C.J., et al. The natural history of epilepsy in tuberous sclerosis
complex. Epilepsia. 2010: 51(7): 1236-1241.
[3] European Medicines Agency. Orphan drugs and rare diseases at a glance.
Available at
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/01/WC500069805.p
df. Accessed December 2016.
[4] Budde, K. and Gaedeke, J. Tuberous sclerosis complex-associated
angiomyolipomas: focus on mTOR inhibition. American Journal of Kidney Diseases.
2012:276-283.
[5] Afinitor (everolimus) Prescribing information. East Hanover, New Jersey,
USA: Novartis Pharmaceuticals Corporation; February 2016.
[6] Votubia (everolimus): EU Summary of Product Characteristics. Novartis;
December 2015.
[7] National Institute of Neurological Disorders and Stroke fact sheet. 2010.
[8]Wong, M. Mammalian target of rapamycin (mTOR) pathways in neurological
diseases. Biomed Journal. 2013; 36(2): 1-17.
[9] Ostendorf, A. and Wong, M. mTOR inhibition in epilepsy: rationale and
clinical perspectives. CNS Drugs. 2015:91-99.
[10] Northrup, H. et al. Tuberous sclerosis complex diagnostic criteria update:
recommendations of the 2012 international tuberous sclerosis complex consensus
conference. Pediatric Neurology. 2013; 49: 243-254
# # #
Novartis Media Relations
Central media line: +41 61 324 2200
E-mail: media.relations(at)novartis.com
Eric Althoff Jeannie Neufeld
Novartis Global Media Relations Novartis Division Communications
+41 61 324 7999 (direct) +1 862 778 2104 (direct)
+41 79 593 4202 (mobile) +1 201 650 2728 (mobile)
eric.althoff(at)novartis.com jeannie.neufeld(at)novartis.com
Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations(at)novartis.com
Central North America
Samir Shah +41 61 324 7944 Richard Pulik +1 212 830 2448
Pierre-Michel Bringer +41 61 324 1065 Sloan Pavsner +1 212 830 2417
Thomas Hungerbuehler +41 61 324 8425
Isabella Zinck +41 61 324 7188
Media release (PDF):
http://hugin.info/134323/R/2065904/775568.pdf
This announcement is distributed by Nasdaq Corporate Solutions on behalf of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.
Source: Novartis International AG via GlobeNewswire
Unternehmensinformation / Kurzprofil:
Datum: 16.12.2016 - 13:23 Uhr
Sprache: Deutsch
News-ID 513455
Anzahl Zeichen: 19929
contact information:
Town:
Basel
Kategorie:
Business News
Diese Pressemitteilung wurde bisher 272 mal aufgerufen.
Die Pressemitteilung mit dem Titel:
"Novartis drug Votubia® recommended by CHMP for EU approval to treat refractory partial-onset seizures in patients with TSC"
steht unter der journalistisch-redaktionellen Verantwortung von
Novartis International AG (Nachricht senden)
Beachten Sie bitte die weiteren Informationen zum Haftungsauschluß (gemäß TMG - TeleMedianGesetz) und dem Datenschutz (gemäß der DSGVO).
