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DIR Return to: OCREVUS (ocrelizumab)
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#Post#: 1198--------------------------------------------------
(AAN) Ocrelizumab better than interferon at halting RRMS disease
activity
By: agate Date: April 28, 2016, 2:28 pm
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From MedPage Today, April 22, 2016:
[quote]Novel Drug Bests Interferon at Halting MS Activity
Nearly half of patients on ocrelizumab achieved no evidence of
disease activity (NEDA)
by Kristina Fiore
Associate Editor, MedPage Today
VANCOUVER -- The investigational B-cell monoclonal antibody
ocrelizumab beat out interferon at stifling disease activity in
multiple sclerosis over 2 years, researchers reported here.
In the OPERA I & II trials, with a significantly larger
proportion of patients on the experimental treatment achieving
no evidence of disease activity (NEDA) (48% versus 29% and 25%,
respectively), Anthony Traboulsee, MD, of the University of
British Columbia in Vancouver, reported at the American Academy
of Neurology meeting here.
Ocrelizumab is an anti-CD20+ monoclonal antibody targeting
B-cells. Most available immunosuppresive therapies for MS target
T-cells, but researchers now theorize that B-cells may also play
an important role in MS.
In fact, ocrelizumab would not be the first B-cell targeting
therapy used in MS. Some physicians currently use rituximab
off-label to treat the condition.
Both rituximab and ocrelizumab are made by Roche/Genentech,
which had tested rituximab in both progressive and
relapsing-remitting MS with promising results before deciding
not to fund further trials. Researchers said that while
rituximab is chimeric, ocrelizumab is a fully humanized
monoclonal antibody that binds more tightly to its target than
the older drug, so infusion reactions and anti-drug antibody
responses may be lessened.
NEDA in RRMS
In OPERA I & II, NEDA was a composite of no relapses, no
confirmed disability progression, no new or enlarging
gadolinium-enhancing T1 lesions, and no new or enlarging T2
lesions.
Patients were randomized to ocrelizumab 600-mg infusion every 24
weeks or to interferon beta three times a week for 96 weeks.
Investigators previously reported a reduction in the annualized
relapse rate with ocrelizumab in both trials compared with
interferon, with a 46% relative reduction in OPERA I and a 47%
relative reduction in OPERA II.
In the latest analysis, they found that significantly more
ocrelizumab patients achieved NEDA compared with those treated
with interferon (48% versus 29% in OPERA I and 48% versus 25% in
OPERA II).
That translated to a 64% to 89% relative increase in preventing
disease activity (P<0.0001 for both), Traboulsee said.
When breaking down NEDA by individual component, larger
proportions of those on ocrelizumab were:
~Without relapses: about 80% versus 65%
~Without 12-week confirmed disability progression: about 90%
versus 85%
~Without gadolinium-enhancing T1 lesions: 90% versus 65%
~Without new or enlarging T2 lesions: 60% versus 38%
"Ocrelizumab for relapsing MS is an extremely important step
forward," David Hafler, MD, of Yale University, who was not
involved in the study, told MedPage Today. "The risk of
progressive multifocal leukencephalopathy seems to be relatively
low. It appears to be, by MRI criteria, the most effective
treatment yet."
Hafler said MS clinicians will probably use it as a first-line
drug, as long as the safety profile "remains as we've seen."
Raghav Govindarajan, MD, of the University of Missouri, who was
also not involved in the study, called the drug "very promising"
for relapsing MS.
"This changes the way we think about MS as a disease," he told
MedPage Today. "Other medications like natalizumab work on T
cells, and that is how we have predominantly thought about MS."
No New PPMS Data
Researchers also reported the results of the 732-patient
ORATORIO trial during a poster session, but these were not much
different from those previously reported at ECTRIMS in
Barcelona, Traboulsee said. The drug reduced the relative risk
of 12-week clinical disability progression by 24% (HR 0.76,
P=0.0321).
The trial enrolled younger patients who'd had a shorter duration
of progressive disease than in past progressive MS trials.
"This is the first treatment to crack open the door to show that
progressive MS is treatable," Traboulsee told MedPage Today.
"Now that we know that the treatment works -- partially, but it
works -- we can now better explore why it works and we can
improve on that so we get a bigger impact on patients."
Traboulsee noted that "everything is more effective in relapsing
MS because we understand the mechanisms better. We are still
struggling to figure out why people progress."
Hafler said the effect seen in the ORATORIO trial "was modest at
best. We badly need to understand PPMS in its varied forms. Yes,
it will probably get approved, and yes, we will use it, but we
need to do better."
Govindarajan said it will be an improvement that he will be able
to offer progressive MS patients something that has been shown
to treat their condition, not just co-occurring symptoms.
"Right now all I can do is provide support," he said. "I don't
have much to offer. I can get them a wheelchair. I can give
Botox for the spasticity. I can help them with swallowing. But
if this medication is shown to work, it can make a difference
for these patients."
A Familiar Situation
It remains to be seen whether ocrelizumab beats out rituximab at
slowing disease activity in MS, although this is a trial that
isn't likely to be done given that Roche/Genentech manufacture
both products.
The companies are no strangers to having two competing drugs for
a single condition, with one offered at a significantly cheaper
price. Roche/Genentech manufacture both bevacizumab (Avastin)
and ranibizumab (Lucentis) for a host of ophthalmic conditions,
and physicians have long preferred the less costly bevacizumab,
especially after studies largely showed equal efficacy and
safety profiles between the two.
Whether such a situation will arise with rituximab-ocrelizumab
remains speculative, but biosimilars for rituximab are expected
to be introduced eventually, at which point market pressures may
force Roche/Genentech to drop the price for rituximab.
_________________
Traboulsee disclosed financial relationships with Biogen,
Hoffman-LaRoche, Genzyme, Serono, and Teva.[/quote]
The article can be seen here
HTML http://www.medpagetoday.com/MeetingCoverage/AAN/57468?xid=nl_mpt_DHE_2016-04-22&eun=g345846d0r.
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