Novartis Drug Gilenya Shows Long-Term Efficacy and Safety According to New Data From Extension of Phase III Head-to-Head Study
• Data from single-arm extension of head-to-head TRANSFORMS
study show sustained reduction in relapses and rate of brain volume
loss in patients on continuous Gilenya treatment for up to 4.5
years
• Reductions in relapses and MRI measures were observed in
patients who switched from Avonex® (interferon-beta-1a IM) to
Gilenya for study extension phase
• Extension study results demonstrated once-daily oral Gilenya
was generally well-tolerated with a safety profile consistent with
pivotal trials
• As of February 2012, approximately 36,000 patients have been
treated in clinical trials and in the post-marketing setting
Basel, June 11, 2012 - New long-term data for Gilenya®
(fingolimod), the only oral therapy approved to treat people with
relapsing forms of multiple sclerosis (MS), show a sustained
efficacy benefit and a consistent safety profile with up to 4.5
years of continuous treatment[1]. These results, from an extension
of the phase III head-to-head TRANSFORMS study, also showed
improved efficacy for patients switched to Gilenya from Avonex®
(interferon-beta-1a IM), a commonly prescribed MS
treatment[1].
"These data further reinforce our confidence in Gilenya's long-term
effectiveness and safety profile. The TRANSFORMS extension study
shows that MS patients treated continuously with Gilenya for up to
four and a half years demonstrated sustained low levels of clinical
and MRI activity," said Tim Wright, Global Head of Development,
Novartis Pharma. "Furthermore, patients who switched to Gilenya
from interferon beta-1a IM showed a reduction in relapses and
improvements in MRI measures in the extension compared to the core
study."
In the core TRANSFORMS study, Gilenya demonstrated superior
efficacy to interferon-beta- 1a IM, reducing the annualized relapse
rate (ARR) by 52% at one year (Gilenya 0.5 mg, ARR = 0.16;
interferon-beta- 1a IM, ARR = 0.33; p<0.001)[2]. The extension
study showed that this low relapse rate was sustained in patients
receiving continuous treatment with Gilenya (n=356) for up to 4.5
years (Gilenya 0.5 mg, ARR core study = 0.16; ARR extension study =
0.16). The data from the extension study also showed that patients
treated with Gilenya continuously maintained a low brain atrophy
rate throughout the study as measured by assessing brain volume
loss, which is valued as a predictor of long-term
disability[1].
For patients who switched to Gilenya for the open-label extension
study (n=167), their ARR was 0.33 in the core study when treated
with interferon-beta-1a IM and 0.20 in the extension phase when
treated with Gilenya (n.s.). Patients in the switch group also
displayed a slowing of brain atrophy following the switch to
Gilenya[1],[2].
These extension data from up to 4.5 years also showed long-term
treatment with Gilenya was generally well tolerated with a safety
profile consistent with pivotal trials. In line with previous
studies, including the core TRANSFORMS study, the most common
adverse events were nasopharyngitis, headache, and upper
respiratory tract infections[2].[3]. Switching therapy from IFN
beta-1a to Gilenya did not reveal any new or unexpected safety
concerns. On treatment initiation, a low incidence of asymptomatic
transient bradycardia was observed in patients who switched from
interferon-beta-1a IM to Gilenya (IFN-0.5 mg [0.6%]), which
resolved without treatment. Overall cardiac events were similar
across all patient groups[3].
In addition, all patients treated with Gilenya in the extension
phase, regardless of original treatment in the core study, showed
comparable percentage of patients free from MRI disease activity by
the end of the study. (Free from Gd enhanced T1 lesions: 77.4% in
switch group vs. 74.7% Gilenya 0.5mg; Free from new/newly enlarged
T2 lesions: 45.0% in switch group vs. 42.0% Gilenya 0.5mg). The
continuous and switch groups did not significantly differ with
respect to disability progression at the end of the study[1].
"This extension study data provide deeper insight into the efficacy
and safety profile of fingolimod, said Dr. Xavier Montalban,
Director of the Multiple Sclerosis Center of Catalonia and of the
Unit of Clinical Neuroimmunology, Vall d'Hebron University
Hospital, Barcelona, Spain. "The results, which are consistent with
the pivotal phase III studies, confirm that fingolimod is highly
effective in treating relapsing forms of MS, and as the first
available oral MS treatment, continues to be a valuable treatment
option for appropriate patients."
TRANSFORMS was a large phase III double-blind, double-dummy,
head-to-head study that involved 1,292 patientswith
relapsing-remitting MS that was conducted over one year, comparing
the efficacy and safety of Gilenya to interferon-beta-1a IM[2]. At
the end of the 12-month core study, eligible patients could enroll
in the extension study, which ran for an additional 3.5 years.
Patients on once-daily oral Gilenya remained on drug and those who
had been treated with interferon-beta-1a (IM) switched to Gilenya
for the duration of the extension study[1].
These data were presented at the 22nd Annual Meeting of the
European Neurological Society (ENS), taking place 9-12 June 2012 in
Prague, Czech Republic.
As of February 2012, approximately 36,000 patients have been
treated with fingolimod in clinical trials and in the
post-marketing setting, some up to seven years, and currently there
is approximately 34,000 patient years of exposure.
About Gilenya
Gilenya, licensed from Mitsubishi Tanabe Pharma Corporation, is the
first in a new class of compounds called sphingosine 1-phosphate
receptor (S1PR) modulators. It has demonstrated superior efficacy
compared to Avonex, a commonly prescribed treatment, showing a 52%
relative reduction in annualized relapse rate (primary endpoint)
and a 40% relative reduction in the rate of brain atrophy
(secondary endpoint) at one year in a pivotal head-to-head trial in
patients with relapsing-remitting multiple sclerosis[2]. In a
recent sub-analysis, Gilenya showed a 61% relative reduction in
annualized relapse rate compared to interferon-beta-1a (IM) at one
year in subgroups of patients with highly active
relapsing-remitting MS not responding to interferon
treatment[4].
Gilenya is generally a highly effective once-daily oral MS
treatment. In clinical trials it was generally well tolerated with
a manageable safety profile, and there is increasing experience of
Gilenya's long-term effectiveness and safety profile, with
approximately 36,000 patients having been treated in clinical
trials and in a post-marketing setting[5]. Currently, there is
approximately 34,000 patient years of exposure. In clinical trials,
the most common side effects were headache, liver enzyme
elevations, influenza, diarrhea, back pain, and cough. Other
Gilenya-related side effects included transient, generally
asymptomatic, heart rate reduction and atrioventricular block upon
treatment initiation, mild blood pressure increase, macular edema,
and mild bronchoconstriction[2],[5],[6].
The rates of infections overall, including serious infections, were
comparable among treatment groups, although a slight increase in
lower respiratory tract infections (primarily bronchitis) was seen
in patients treated with Gilenya. The number of malignancies
reported across the clinical trial program was small, with
comparable rates between the Gilenya and control
groups[2],[6].
Disclaimer
The foregoing release contains forward-looking statements that can
be identified by terminology such as "confidence," or similar
expressions, or by express or implied discussions regarding
potential new indications or labeling for Gilenya or regarding
potential future revenues from Gilenya. 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 Gilenya to be materially
different from any future results, performance or achievements
expressed or implied by such statements. There can be no guarantee
that Gilenya 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 Gilenya will achieve any
particular levels of revenue in the future. In particular,
management's expectations regarding Gilenya 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; competition in general;
government, industry and general public pricing pressures;
unexpected manufacturing issues; the company's ability to obtain or
maintain patent or other proprietary intellectual property
protection; 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 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, cost-saving generic
pharmaceuticals, preventive vaccines and diagnostic tools,
over-the-counter and animal health products. Novartis is the only
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Group's continuing operations achieved net sales of USD 58.6
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References:
1. Khatri B. et al. Long-term efficacy data from the extension of
the phase III TRANSFORMS study of fingolimod versus interferon
beta-1a in relapsing-remitting multiple sclerosis: 4.5 year
follow-up. Abstract Presented at ENS, Prague, June 2012.
2. Cohen J. et al. Oral Fingolimod vs. Intramuscular Interferon in
Relapsing Multiple Sclerosis. N Eng J Med. Vol.362 No.5, Feb 4,
2010;362:402-415.
3. Hartung HP. et al. Long-term safety data from the extension of
the phase III TRANSFORMS study of fingolimod versus interferon
beta-1a in relapsing-remitting multiple sclerosis: Abstract
Presented at ENS, Prague, June 2012.
4. Havrdová E. et al. Clinical outcomes in subgroups of
patients with highly action relapsing-remitting multiple sclerosis
treated with Fingolimod (FTY720): Results from the FREEDOMS and
TRANSFORMS phase III studies. Poster presented at ECTRIMS,
Amsterdam, October 2011.
5. Data on file.
6. Kappos L, et al. Placebo-Controlled Study of Oral Fingolimod in
Relapsing Multiple Sclerosis. N Eng J Med. Vol.362 No.5, Feb 4,
2010; 362:387-401.
Avonex® is a registered trademark of Biogen Idec.
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Posted: June 2012
