MS Speaks
Multiple Sclerosis => TREATMENTS => TYSABRI (natalizumab) => Topic started by: agate on April 22, 2016, 05:14:05 pm
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From MedPage Today, April 22, 2016:
Tysabri No Help in SPMS
Drug didn't reduce disability progression but may benefit upper limb function
by Kristina Fiore
Associate Editor, MedPage Today
VANCOUVER -- Natalizumab (Tysabri) didn't slow disability progression in patients with secondary progressive multiple sclerosis (SPMS), researchers reported here.
The ASCEND trial missed its primary endpoint of reducing progression as measured by a composite endpoint assessing disability unrelated to relapses, Deborah Steiner, MD, of Biogen, reported during the emerging science session at the American Academy of Neurology meeting here.
But Steiner noted that there was a significant benefit on upper extremity function.
"There's a striking contrast between the lack of effect on ambulatory function as measured by the timed 25-foot walk test, and the effects on upper extremity function as measured by the 9-hole peg test," she said.
There are currently no approved therapies for primary progressive or secondary progressive MS -- although data reported here on ocrelizumab, an investigational B-cell targeting therapy by Roche/Genentech, suggested the drug has some efficacy in primary progressive disease.
Still, there is little to offer patients with secondary progressive disease, Steiner said. Natalizumab is highly effective in relapsing MS, although it carries a higher risk of progressive multifocal leukoencephalopathy (PML) than many of the other relapsing MS therapies.
To assess whether it may be able to slow disability progression unrelated to relapses in secondary progressive MS, the researchers conducted the ASCEND trial in patients who'd had SPMS for at least 2 years and who had disability progression unrelated to relapses in the prior year. None of them had been previously treated with natalizumab.
The primary endpoint was a binary outcome of confirmed disability progressors or non-progressors on a composite endpoint of Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk Test (T25FW), and 9-Hole Peg Test (9HPT). This endpoint was designed to capture the treatment effects on key aspects of disability progression in SPMS, Steiner said.
A total of 887 patients randomized to placebo or 300 mg natalizumab infusion every 4 weeks for 96 weeks.
Most of the patients had advanced disability at baseline, with 63% having an EDSS score in the range of 6.0 to 6.5, and scores on the 9HPT suggested more lower-limb impairment than upper-limb.
Overall, the trial did not meet its primary endpoint, although a slightly smaller proportion of patients on natalizumab were progressors than those on placebo (44% versus 48%), she reported.
The drug did, however, show a statistically significant treatment effect on reducing upper-limb disability progression unrelated to relapse as measured by the 9HPT, with fewer progressors (15% versus 23%, OR 0.56, P=0.0012).
Natalizumab was generally well tolerated, she added, with adverse events that were consistent with its known safety profile.
Steiner concluded that while natalizumab didn't delay the progression of ambulatory disability in SPMS, it was associated with significant slowing of upper-extremity disability progression and reduction of relapses and MRI activity.
"The majority of patients had advanced disability, representing a global SPMS population for whom there is currently no effective therapy able to treat disability progression unrelated to relapses," she said.
She added that the lack of treatment effects on ambulatory function underscores the importance of treating MS early with effective therapies like natalizumab.
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Steiner disclosed no financial relationships with industry. Co-authors reported financial relationships with several MS drugmakers.