Contributions
Abstract: P786
Type: Poster
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Objectives: MS-SPI was a 12-month (M) double-blind study where patients (pts; n=154) with non-active progressive multiple sclerosis (PMS) were randomised to MD1003 (n=103) or placebo (n=51). In the open-label extension phases, all pts received MD1003. Here, we present the 36M results (shown as MD1003>MD1003 [MM] vs placebo>MD1003 [PM]).
Methods: The extension phase included 133 pts (MM: 91; PM: 42). At M12, M24 and M36 we analysed: confirmed Expanded Disability Status Scale (EDSS) or timed 25-foot walk (TW25) improvement; mean EDSS change from baseline (mEDSS); TW25 evolution; and Clinician and Subject Global Impression of Change scale (CGI and SGI).
Results: EDSS or TW25 improvement was significantly higher for MM vs PM pts at M9 (13% vs 0%,
P< 0.05; confirmed at 3M); the trend was similar at M18 (13% vs 7%) and M30 (10% vs 2%; both confirmed after 6M).
mEDSS slightly decreased in MM and worsened in PM pts at M12 (−0.03 vs 0.13, P=0.01). When all patients were treated with MD1003 after M12, mEDSS remained stable and there was no significant difference between groups (M24: 0.04 vs 0.15, P=0.13; M36: 0.09 vs 0.18, P=0.35). However, the 2 mEDSS evolution curves remained parallel suggesting that earlier treatment leads to a lower disability at M36.
The proportion of pts unable to complete TW25 (or with time >180 sec) increased in both groups before M12, with a trend for less increase in MD1003 treated pts (baseline: 1% vs 2%; M12: 6% vs 19%). This proportion remained quite stable in all pts in year 2 (M24: 13% vs 20%) and in MM patients in year 3, but increased again in PM pts in year 3 (M36: 13% vs 30%).
CGI and SGI results were significantly better in favour of the MD1003 group at M12 (CGI: 4.05 vs 4.62, P< 0.0001; SGI: 4.27 vs 4.76, P=0.009). After M12, scores remained stable for MM pts and improved for PM pts, and the difference was no longer significant at M24 (CGI: 4.17 vs 4.21, P=0.93; SGI: 4.47 vs 4.41, P=0.75) or M36 (CGI: 4.11 vs 4.09, P=0.88; SGI: 4.11 vs 4.03, P=0.86).
At M36, adverse events were experienced by 67% vs 79% of pts in MM and PM groups.
Discussion: These results indicate that: MD1003 effects seem sustainable over time; disease progression halts when pts switch from placebo to MD1003; delayed treatment in PM pts results in higher disability over time; and MD1003 is well tolerated over 36M.
These data suggest that targeting neuronal metabolism in PMS might represent a new class of long-term disease-modifying therapy.
Disclosure:
Sandra Vukusic has received consultancy fees, speaker fees, research grants (non-personal) or honoraria from Biogen, GeNeuro, Sanofi Genzyme, MedDay, Merck-Serono, Novartis, Roche and Teva.
Jerome De Seze has nothing to disclose.
Gilles Edan has received personal fees from Bayer, and grants and personal fees from Merck Serono, Teva, Biogen Idec, Novartis and Sanofi.
Thibault Moreau has received consultancy fees, speaker fees, research supports, or honoraria from Novartis, Biogen Idec, Merck, Roche, MedDay, Teva and Sanofi Genzyme.
Bruno Brochet has received consultancy fees, speaker fees, research grants (non-personal), or honoraria from Novartis, Biogen Idec, Merck, Roche, MedDay, Bayer, Actelion, Teva and Sanofi Genzyme.
Robert Lasser has nothing to disclose.
Ayman Tourbah has received, in the last year, consulting and lecturing fees, travel grants and research support from MedDay, Biogen Idec, Sanofi-Genzyme, Novartis, Merck Serono, Teva and Roche.
Abstract: P786
Type: Poster
Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS
Objectives: MS-SPI was a 12-month (M) double-blind study where patients (pts; n=154) with non-active progressive multiple sclerosis (PMS) were randomised to MD1003 (n=103) or placebo (n=51). In the open-label extension phases, all pts received MD1003. Here, we present the 36M results (shown as MD1003>MD1003 [MM] vs placebo>MD1003 [PM]).
Methods: The extension phase included 133 pts (MM: 91; PM: 42). At M12, M24 and M36 we analysed: confirmed Expanded Disability Status Scale (EDSS) or timed 25-foot walk (TW25) improvement; mean EDSS change from baseline (mEDSS); TW25 evolution; and Clinician and Subject Global Impression of Change scale (CGI and SGI).
Results: EDSS or TW25 improvement was significantly higher for MM vs PM pts at M9 (13% vs 0%,
P< 0.05; confirmed at 3M); the trend was similar at M18 (13% vs 7%) and M30 (10% vs 2%; both confirmed after 6M).
mEDSS slightly decreased in MM and worsened in PM pts at M12 (−0.03 vs 0.13, P=0.01). When all patients were treated with MD1003 after M12, mEDSS remained stable and there was no significant difference between groups (M24: 0.04 vs 0.15, P=0.13; M36: 0.09 vs 0.18, P=0.35). However, the 2 mEDSS evolution curves remained parallel suggesting that earlier treatment leads to a lower disability at M36.
The proportion of pts unable to complete TW25 (or with time >180 sec) increased in both groups before M12, with a trend for less increase in MD1003 treated pts (baseline: 1% vs 2%; M12: 6% vs 19%). This proportion remained quite stable in all pts in year 2 (M24: 13% vs 20%) and in MM patients in year 3, but increased again in PM pts in year 3 (M36: 13% vs 30%).
CGI and SGI results were significantly better in favour of the MD1003 group at M12 (CGI: 4.05 vs 4.62, P< 0.0001; SGI: 4.27 vs 4.76, P=0.009). After M12, scores remained stable for MM pts and improved for PM pts, and the difference was no longer significant at M24 (CGI: 4.17 vs 4.21, P=0.93; SGI: 4.47 vs 4.41, P=0.75) or M36 (CGI: 4.11 vs 4.09, P=0.88; SGI: 4.11 vs 4.03, P=0.86).
At M36, adverse events were experienced by 67% vs 79% of pts in MM and PM groups.
Discussion: These results indicate that: MD1003 effects seem sustainable over time; disease progression halts when pts switch from placebo to MD1003; delayed treatment in PM pts results in higher disability over time; and MD1003 is well tolerated over 36M.
These data suggest that targeting neuronal metabolism in PMS might represent a new class of long-term disease-modifying therapy.
Disclosure:
Sandra Vukusic has received consultancy fees, speaker fees, research grants (non-personal) or honoraria from Biogen, GeNeuro, Sanofi Genzyme, MedDay, Merck-Serono, Novartis, Roche and Teva.
Jerome De Seze has nothing to disclose.
Gilles Edan has received personal fees from Bayer, and grants and personal fees from Merck Serono, Teva, Biogen Idec, Novartis and Sanofi.
Thibault Moreau has received consultancy fees, speaker fees, research supports, or honoraria from Novartis, Biogen Idec, Merck, Roche, MedDay, Teva and Sanofi Genzyme.
Bruno Brochet has received consultancy fees, speaker fees, research grants (non-personal), or honoraria from Novartis, Biogen Idec, Merck, Roche, MedDay, Bayer, Actelion, Teva and Sanofi Genzyme.
Robert Lasser has nothing to disclose.
Ayman Tourbah has received, in the last year, consulting and lecturing fees, travel grants and research support from MedDay, Biogen Idec, Sanofi-Genzyme, Novartis, Merck Serono, Teva and Roche.