DIR Return Create A Forum - Home
---------------------------------------------------------
MS Speaks
HTML https://msspeaks.createaforum.com
---------------------------------------------------------
*****************************************************
DIR Return to: PLEGRIDY (pegylated interferon beta-1a)
*****************************************************
#Post#: 189--------------------------------------------------
Plegridy (PEGylated interferon beta-1a) (BIIB017)
By: agate Date: February 26, 2014, 5:45 pm
---------------------------------------------------------
Another interferon, PLEGRIDY, will probably be coming along
soon.
From the MSAA 2014 MS Research Update:
[quote]Plegridy® PEGylated interferon beta-1a, also known as
BIIB017)
Company: Biogen Idec
Administered by subcutaneous injection once every two weeks at a
dose of 125 mcg (micrograms)
Plegridy is being studied for relapsing forms of MS
PEGylation is a chemical modification that has been performed on
the interferon beta-1a molecule that allows it to be given
subcutaneously (under the skin) every two or four weeks, in
contrast to the more frequent injections utilized by the
currently approved forms of interferon. The goal is to reduce
the number of injections, while maintaining the positive effect
of the drug.
Studies have tested this experimental therapy for safety and
effectiveness. If approved by the FDA, this would give patients
the option of using a single-dose auto-injector with a prefilled
syringe less frequently.
The Phase III clinical trial (ADVANCE) enrolled patients with
relapsing-remitting MS (RRMS) to determine the safety and
efficacy of Plegridy as compared to placebo. Results were
presented in 201331 from the first year of this Phase III study,
where 1,512 patients were randomized to one of three groups: one
group receiving placebo; a second group receiving Plegridy given
by subcutaneous injection once every two weeks; and a third
group receiving Plegridy by subcutaneous injection once every
four weeks.
Plegridy dosed every two weeks significantly reduced MS disease
activity versus placebo. Relapses were reduced by 36 percent,
and new brain lesions by 67 percent, compared to placebo at one
year. Disability outcomes were also positive in this one-year
trial. In total, the proportion of disease activity-free
patients over one year was significantly higher in the two
treatment groups compared to placebo.
The overall incidence of serious adverse events (SAE) and
adverse events (AE) was similar among the Plegridy and placebo
groups. The most common serious adverse event was infection,
which was balanced across all treatment groups (less than or
equal to 1 percent per group). The most commonly reported
adverse events with Plegridy treatment were redness at the
injection site and influenza-like illness. Flu-like illness was
reported in 47 percent of both treatment groups compared to 13
percent in the placebo group. These safety data are consistent
with the established safety profile of interferon beta-1a
therapies for MS.
After the first year, study participants who were taking the
placebo were re-randomized to one of the two treatment groups
(taking the active drug either once every two weeks or once
every four weeks), and will continue on their new treatment for
the remainder of the second year in the study. Once the study is
completed, participants will be given the option to enroll in
the ATTAIN open-label (no longer blinded) extensions study.
Participants will be followed for up to four years in this
second study.
In a subgroup of ADVANCE participants, up to 120 were enrolled
in a sub-study that involves optical coherence tomography (OCT).
This is a rapid, noninvasive, office-based imaging technique
that allows objective evaluation of the thickness of the retinal
axon (the nerve behind the eye) and nerve layers that atrophy
(shrinking due to nerve cell death) in MS. Preliminary evidence
supports the use of OCT as an objective tool to monitor the
effectiveness of a therapy, and it is hoped that OCT may be used
as an outcome measure in future studies.
In May 2013, Biogen Idec submitted a new treatment application
for multiple sclerosis to the United States FDA for approval,
and the application was accepted for review. A decision
regarding the approval of Plegridy is expected in 2014.[/quote]
#Post#: 285--------------------------------------------------
(AAN) Peginterferon Beta-1a may improve recovery after relapses.
..
By: agate Date: May 5, 2014, 6:17 pm
---------------------------------------------------------
A Biogen-sponsored study, presented at the annual AAN conference
in Philadelphia, April 29, 2014:
[quote][S4.003] Peginterferon Beta-1a May Improve Recovery
Following Relapses: Data from the Pivotal Phase 3 ADVANCE Study
in Patients with Relapsing-Remitting Multiple Sclerosis
Bernd Kieseier,1Thomas Scott,2Scott Newsome,3Sarah
Sheikh,4Serena Hung,4Xiaojun You,5Bjorn Sperling5
1Düsseldorf, Germany, 2Pittsburgh, PA, USA, 3Baltimore, MD, USA,
4Cambridge, MA, USA, 5Weston, MA, USA
OBJECTIVE:
To determine whether peginterferon beta-1a improved recovery
following relapses in patients with relapsing-remitting multiple
sclerosis (RRMS).
BACKGROUND: In Year 1 of the ADVANCE study, subcutaneous
peginterferon beta-1a (125 µg) every 2 (Q2W) or 4 (Q4W) weeks
significantly reduced, versus placebo, the risk of 12-week
confirmed disability progression (by 38% in both dosing arms),
and annualized relapse rate (ARR; by 36% and 28%, respectively).
In RRMS populations treated with placebo, approximately 20-30%
of all relapses have been reported to lead to confirmed
disability progression. However, approximately half of patients
experiencing disability progression do so without associated
relapses. Thus, a reduction in ARR alone may not explain the
reduced risk of disability progression with peginterferon
beta-1a in the ADVANCE study.
DESIGN/METHODS:
Post-hoc analyses were conducted using data from 1512 patients
who were randomized and dosed in ADVANCE. Disability progression
due to incomplete recovery following relapse was defined as
onset of 3-month sustained disability progression (≥1.0-
or ≥1.5-point increase in Expanded Disability Status Scale
score, from a baseline score of ≥1.0 or 0.0, respectively,
confirmed after 12 weeks) within 180 days of a relapse.
RESULTS:
Overall, n=55 experienced disability progression associated with
relapses; n=57 experienced disability progression not associated
with relapses (numerically fewer patients on peginterferon
beta-1a versus placebo). Relapse severities were not different
between groups. Peginterferon beta-1a Q2W and Q4W reduced the
proportion of patients experiencing sustained disability
progression due to incomplete recovery following a relapse
versus placebo by 56% (p=0.012) and 41% (p=ns), respectively.
Following a recent relapse, a lower proportion receiving
peginterferon beta-1a Q2W (13.6%) and Q4W (15.2%) had sustained
disability progression versus placebo (19.6%); indicating
relative reductions in risk of progression following any relapse
of 30% and 22%, respectively.
CONCLUSIONS:
The significant reduction in risk of disability progression at
Year 1 in ADVANCE observed in patients treated with
peginterferon beta-1a versus placebo may be partially due to
greater recovery from relapses.
Study Sponsored by: Biogen Idec Inc.
Category - MS and CNS Inflammatory Disease: Clinical Science
S4: Platform Session: MS and CNS Inflammatory Disease: Clinical
Trials
[/quote]
#Post#: 286--------------------------------------------------
(Abst.) Pegylated interferon beta-1a for RRMS: ADVANCE study
By: agate Date: May 6, 2014, 6:35 pm
---------------------------------------------------------
From PubMed, May 6, 2014:
[quote]Lancet Neurol. 2014 Apr 30. pii: S1474-4422(14)70068-7.
Pegylated interferon beta-1a for relapsing-remitting multiple
sclerosis (ADVANCE): a randomised, phase 3, double-blind study
Calabresi PA1, Kieseier BC2, Arnold DL3, Balcer LJ4, Boyko A5,
Pelletier J6, Liu S7, Zhu Y7, Seddighzadeh A7, Hung S7, Deykin
A7; for the ADVANCE Study Investigators.
Author information
1Department of Neurology, Johns Hopkins University, Baltimore,
MD, USA. Electronic address: pcalabr1@jhmi.edu.
2Department of Neurology, Medical Faculty, Heinrich-Heine
University, Düsseldorf, Germany.
3Montreal Neurological Institute, McGill University, Montreal,
QC, Canada; NeuroRx Research, Montreal, QC, Canada.
4Department of Neurology, New York University, Langone Medical
Center, New York, NY, USA.
5Moscow MS Center at 11 City Hospital and Department of
Neurology & Neurosurgery of the RSMRU named by Pirogov, Moscow,
Russia.
6Departments of Neurology and Research (CRMBM), CHU Timone,
Marseille, France.
7Biogen Idec, Cambridge, MA, USA.
BACKGROUND:
Subcutaneous pegylated interferon (peginterferon) beta-1a is
being developed for treatment of relapsing multiple sclerosis,
with less frequent dosing than currently available first-line
injectable treatments. We assessed the safety and efficacy of
peginterferon beta-1a after 48 weeks of treatment in the
placebo-controlled phase of the ADVANCE trial, a study of
patients with relapsing-remitting multiple sclerosis.
METHODS:
We did this 2-year, double-blind, parallel group, phase 3 study,
with a placebo-controlled design for the first 48 weeks, at 183
sites in 26 countries. Patients with relapsing-remitting
multiple sclerosis (age 18-65 years, with Expanded Disability
Status Scale score ≤5) were randomly assigned (1:1:1) via
an interactive voice response or web system, and stratified by
site, to placebo or subcutaneous peginterferon beta-1a 125
μg once every 2 weeks or every 4 weeks. The primary
endpoint was annualised relapse rate at 48 weeks. This trial is
registered with ClinicalTrials.gov, number NCT00906399.
FINDINGS:
We screened 1936 patients and enrolled 1516, of whom 1512 were
randomly assigned (500 to placebo, 512 to peginterferon every 2
weeks, 500 to peginterferon every 4 weeks); 1332 (88%) patients
completed 48 weeks of treatment. Adjusted annualised relapse
rates were 0·397 (95% CI 0·328-0·481) in the placebo group
versus 0·256 (0·206-0·318) in the every 2 weeks group and 0·288
(0·234-0·355) in the every 4 weeks group (rate ratio for every 2
weeks group 0·644, 95% CI 0·500-0·831, p=0·0007; rate ratio for
the every 4 weeks group 0·725, 95% CI 0·565-0·930, p=0·0114).
417 (83%) patients taking placebo, 481 (94%) patients taking
peginterferon every 2 weeks, and 472 (94%) patients taking
peginterferon every 4 weeks reported adverse events including
relapses.
The most common adverse events associated with peginterferon
beta-1a were injection site reactions, influenza-like symptoms,
pyrexia, and headache. 76 (15%) patients taking placebo, 55
(11%) patients taking study drug every 2 weeks, and 71 (14%)
patients taking study drug every 4 weeks reported serious
adverse events; relapse, pneumonia, and urinary tract infection
were the most common.
INTERPRETATION:
After 48 weeks, peginterferon beta-1a significantly reduced
relapse rate compared with placebo. The drug might be an
effective treatment for relapsing-remitting multiple sclerosis
with less frequent administration than available treatments.
FUNDING:
Biogen Idec.
PMID: 24794721[/quote]
The abstract can be seen here
HTML http://www.ncbi.nlm.nih.gov/pubmed/24794721.
#Post#: 384--------------------------------------------------
A better interferon?
By: agate Date: July 9, 2014, 12:43 pm
---------------------------------------------------------
From the MS Discovery Forum "New Findings" (July 2, 2014);
[quote]A Better Interferon?
Subcutaneous injections of pegylated interferon β-1a once
every 2 weeks may improve recovery from relapses and increase
the likelihood of freedom from measurable disease activity
LISA J. BAIN
Pegylated interferon β-1a (PEG-IFN) continues to show
benefits similar to other currently available treatments for
multiple sclerosis (MS), according to data presented at the 2014
American Academy of Neurology (AAN) meeting in Philadelphia.
Pegylation involves the covalent attachment of a polyethylene
glycol (PEG) molecule to a compound as a means of reducing its
immunogenicity and increasing its stability, solubility,
half-life, and efficacy.
In July 2013, MSDF reported preliminary data from the first year
of the phase 3 ADVANCE trial of PEG-IFN (Reuss, 2013). These
results showed that intravenous administration of 125 µg of
PEG-IFN either once every 2 weeks (Q2W) or once every 4 weeks
(Q4W) reduced disability progression by 38% in both dosing arms
as measured by the Expanded Disability Status Scale. It also
reduced annualized relapse rate by 36% (Q2W) and 28% (Q4W).
In Philadelphia, Peter Calabresi, M.D., of Johns Hopkins
University presented 2-year clinical efficacy and safety data
from ADVANCE. These results support maintained benefits of
PEG-IFN Q2W or Q4W beyond 1 year, with the Q2W dosing regimen
showing greater efficacy across all endpoints. In addition,
immunogenicity appears to be extremely low, Calabresi said.
Two other post hoc analyses of ADVANCE data explored other, less
commonly used outcome measures that may better represent
efficacy in MS drug trials. For example, Bernd Kieseier, M.D.,
of Heinrich Heine University in Düsseldorf, Germany, presented
an analysis that asked whether PEG-IFN improves recovery
following relapses. According to Kieseier, reduction in
annualized relapse rate alone may not explain the reduced risk
of disability, since about half of patients experience
disability progression without associated relapses. By comparing
those with disability progression who did or did not have
relapses, this analysis showed that, in comparison to placebo,
significantly fewer patients taking PEG-IFN had disability
resulting from incomplete recovery from relapse; and that
following a relapse, fewer patients receiving PEG-IFN had
sustained disability progression—30% reduced risk of progression
in those taking the drug every 2 weeks, and 22% in those taking
the drug every 4 weeks.
In the other post hoc analysis, Douglas Arnold, M.D., of the
Montreal Neurological Institute at McGill University assessed a
relatively new measure of therapeutic response: freedom from
measured disease activity, or FMDA (also called no evidence of
disease activity, or NEDA) (Havrdova et al., 2010). “In the
current environment of drug development, it’s becoming less and
less acceptable to accept partially effective therapies,” Arnold
said during his platform presentation.
Arnold tested three subtypes of FMDA: clinical FMDA, in which
patients experience no relapses and no sustained accumulation of
disability at 12 weeks; MRI FMDA, in which MR studies show an
absence of gadolinium-enhancing lesions and no new or enlarging
T2 lesions; and the composite of these two, called overall FMDA.
Only patients with complete data were included in these FMDA
analyses. Compared to placebo, significantly higher proportions
of patients receiving PEG-IFN both every 2 weeks and every 4
weeks had overall, clinical, and MRI FMDA. At week 48, 33.9% of
patients in the Q2W treatment group achieved overall FMDA,
compared to 21.5% in the Q4W group and 15.1% of those receiving
placebo.
“I think FMDA is a very attractive endpoint,” Arnold concluded.
“Why should we settle for incomplete control of a focal
inflammatory disease when we know the lesions are associated
with axonal transection and irreversible brain damage, which
accumulates even if the disease is asymptomatic?”
Disclosures and sources of funding
These studies were sponsored by Biogen Idec Inc. Dr. Calabresi
has received personal compensation for activities with Biogen
Idec, Teva Neuroscience, Genzyme Corporation, Vaccinex, Vertex,
and Novartis; and research support from the National Institutes
of Health, the National Multiple Sclerosis Society, Nancy Davis
Foundation, Biogen Idec, Vertex, Genentech Inc., Abbott, and
Bayer.Dr. Arnold has received personal compensation for
activities with Acorda Therapeutics, Bayer Pharmaceuticals
Corporation, Biogen Idec, Coronado Biosciences, EMD Serono,
Genentech Inc., Genzyme Corporation, GlaxoSmithKline Inc.,
MedImmune, and NeuroRx Research. Dr. Arnold has received
research support from Bayer Pharmaceuticals Corporation.
Dr. Kieseier has received personal compensation for activities
with Bayer Pharmaceuticals Corp., Schering AG, Biogen Idec,
Merck Serono, Novartis, Roche Diagnostics Corp., Sanofi-Aventis
Pharmaceuticals Inc., and Teva Neuroscience. Dr. Kieseier has
received research support from Bayer Schering, Biogen Idec,
Merck Serono, and Teva Neuroscience. Co-authors Drs. Sheikh,
Deykin, Zhu, Sperling, Hung, and You have received personal
compensation for activities with Biogen Idec as an employee.
Co-author Dr. Scott has received personal compensation for
activities with Novartis, Biogen Idec, Teva Neuroscience, and
Genzyme Corp., and research support from the Pittsburgh
Foundation. Dr. Newsome has received personal compensation for
activities with Biogen Idec and Genzyme Corp.
[/quote]
The article, along with references and comments, can be seen
here
HTML http://www.msdiscovery.org/news/new_findings/12097-better-interferon#disclosures-and-sources-of-funding.
#Post#: 432--------------------------------------------------
Plegridy approved by US FDA
By: agate Date: August 18, 2014, 9:47 am
---------------------------------------------------------
Plegridy has been given the US FDA's approval. An MSAA article
about it
HTML http://mymsaa.org/news-msaa/1165-plegridy-approved
appeared
today.
#Post#: 469--------------------------------------------------
(ACTRIMS/ECTRIMS): [Plegridy shown to be more effective when giv
en every 2 wks.]
By: agate Date: September 13, 2014, 8:58 pm
---------------------------------------------------------
Presented at the ACTRIMS/ECTRIMS conference in Boston, September
10-13, 2014:
[quote]Clinical efficacy of peginterferon beta-1a in
relapsing-remitting multiple sclerosis: 2-year data from the
phase 3 ADVANCE study
PA Calabresi1, BC Kieseier2, DL Arnold3,4, L Balcer5, A Boyko6,
J Pelletier7, S Liu8, Y Zhu8, SI Sheikh8, A Seddighzadeh8, A
Deykin8, S Hung8
1Johns Hopkins University, Department of Neurology, Baltimore,
MD, United States, 2Heinrich-Heine University, Department of
Neurology, Düsseldorf, Germany, 3Montreal Neurological
Institute, McGill University, Montreal, QC, Canada, 4NeuroRx
Research, Montreal, QC, Canada, 5New York University School of
Medicine, Departments of Neurology and Population Health, New
York, NY, United States, 6Moscow MS Center at RSMU, Moscow,
Russian Federation, 7CHU Timone, Departments of Neurology and
Research (CRMBM), Marseille, France, 8Biogen Idec Inc.,
Cambridge, MA, United States
Background:
At Year 1 of ADVANCE, subcutaneous peginterferon beta-1a (125 µg
every 2 [Q2W] or 4 [Q4W] weeks) significantly reduced annualized
relapse rate [ARR; primary endpoint], risk of relapse, and risk
of 12-week confirmed disability progression versus placebo.
Safety profiles were similar for Q2W and Q4W treatment arms, and
consistent with established interferon beta-1a therapies.
Objectives:
To evaluate the efficacy of peginterferon beta-1a over 2 years
on relapse and disability endpoints in patients with
relapsing-remitting multiple sclerosis (RRMS) in the Phase 3
ADVANCE study.
Methods:
After Year 1, patients randomized to placebo were re-randomized
to 125 µg peginterferon beta-1a administered Q2W or Q4W for Year
2. Patients randomized to peginterferon beta-1a in Year 1
remained on the same dosing regimen in Year 2. All efficacy
analyses were performed on data from the intent-to-treat
population (all randomized patients who received at least one
dose of active study treatment over 2 years). Statistical
analysis of proportion of patients with disability progression
(patients in the original placebo arm in Year 1 versus patients
on peginterferon beta-1a dosing regimens over both years) was
pre-specified whereas all remaining statistical analyses were
post-hoc.
Results:
In Year 2, ARR was further reduced in patients receiving Q2W
(Year 1: 0.230 [95% CI 0.183-0.291], Year 2: 0.178
[0.136-0.233]) and was maintained for patients treated with Q4W
(Year 1: 0.286 [0.231-0.355], Year 2: 0.291 [0.231-0.368]).
Compared to patients originally randomized to placebo in Year 1,
reductions were seen for patients on peginterferon beta-1a
during both Years 1 and 2 in ARR (Q2W 37% [p< 0.0001], Q4W 17%
[p=0.0906]), risk of relapse (Q2W 39% [p< 0.0001], Q4W 19%
[p=0.0465]) and risk of disability progression (12-week
confirmed: Q2W 33% [p=0.0257], Q4W 25% [p=0.0960]; 24-week
confirmed: Q2W 41% [p=0.0137], Q4W 9% [p=0.6243]).
Over 2 years, relative to Q4W dosing, greater reductions were
observed with Q2W dosing in ARR (24%, p=0.0209), risk of relapse
(24%, p=0.0212), and risk of disability progression (12-week
confirmed: 11%, p=0.5665 and 24-week confirmed: 36%, p=0.0459).
Conclusions:
2-year results support the maintained benefits of peginterferon
beta-1a beyond 1 year in RRMS, with significantly greater
efficacy seen for Q2W versus Q4W across relapse endpoints.
[/quote]
*****************************************************