Contributions
Abstract: P568
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Objectives: The POINT study aims to evaluate the safety and efficacy of ponesimod as add-on treatment to dimethyl fumarate (DMF) in patients with relapsing multiple sclerosis (RMS).
Introduction: Despite recent advances in the treatment of RMS, an unmet medical need remains to improve long-term disease control without compromising patient safety. Targeting RMS treatment with a combination of compounds that have different mechanisms of action may reduce disease activity to a level not achieved by any agent alone. Ponesimod, a novel, selective and rapidly reversible sphingosine-1-phosphate receptor modulator, has shown beneficial effects in a Phase 2 study and is currently in Phase 3 clinical development for RMS. Ponesimod acts by sequestering lymphocytes in lymphoid organs, thus reducing their circulation to the brain. DMF exhibits anti-inflammatory and potentially neuroprotective, anti-oxidative effects via inhibition of NF-κB and activation of Nrf-2. In preclinical studies, the combination of ponesimod with DMF showed improved efficacy versus each agent alone without increased toxicity. POINT is the first ever Phase 3 study in RMS where an oral investigational compound is added to oral background therapy approved for RMS.
Methods: Approximately 600 subjects with RMS who have signs of disease activity under ongoing treatment with DMF will be randomized 1:1 to ponesimod 20 mg or placebo as add-on treatment to DMF. Double-blind treatment will continue until the last subject enrolled has been treated for 60 weeks. Key eligibility criteria include a diagnosis of RMS, at least 6 months of ongoing treatment with DMF, stable lymphocyte counts above 800 cells/mm3, and documented clinical and/or MRI disease activity within 12-15 months of screening. The primary efficacy endpoint is the annualized relapse rate, defined as the number of confirmed relapses from randomization to the end of study. Other outcome measures include clinical and MRI disease activity, fatigue, as well as safety and tolerability. Details of the study design and study status will be presented.
Results: Enrolment began in February 2017 and is ongoing.
Conclusion: POINT, as the first Phase 3 study investigating the combination of two oral compounds with different modes of action addressing relevant targets in the pathogenesis of MS, will provide valuable information about possible additive or even synergistic efficacy and the safety of this new treatment concept for RMS.
Disclosure: LK's Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
EL, AL and BH are employees of Actelion Pharmaceuticals. BH holds stock in Johnson and Johnson, Novo Nordisk and Idorsia.
MF has received honoraria from Actelion, Bayer Healthcare, Biogen Idec, Chugai, Clene Nanomedicine, EMD Canada, Genzyme, Hoffman La-Roche, MedDay, Merck Serono, Novartis, Sanofi-Aventis, Teva Canada Innovation, and research support from Genzyme.
RF has received honoraria from Actelion, Biogen, Genentech, Idec, Novartis, Teva, and research support from Biogen and Novartis.
EH has received honoraria from Actelion, Biogen, Celgene, Merck, Novartis, Sanofi Genzyme and Teva.
RH has received honoraria from Actelion, Biogen, Genzyme-Sanofi, Novartis, Roche, and research support from Biogen, Genzyme-Sanofi, Novartis, Roche.
FL has received honoraria from Abbvie, Acorda, Actelion, Akros, Apitope, Atara Biotherapeutics, Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Forward Pharma, Innate Immunotherapeutics, Mapi Pharma, Medday, MedImmune, Novartis, Polpharma, Receptos/Celgene, Regeneron, Roche/Genentech, Sanofi/Genzyme, Teva, TG Therapeutics, Toyama, and research support from Biogen Idec, Celgene; Genzyme, NIH, NMSS, Novartis Pharmaceuticals Corp, Sanofi, Teva Neuroscience, Inc., Transparency Life Sciences.
XM has been a clinical trial steering committee member or participated in advisory boards with Actelion, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Oryzon, Roche, Sanofi-Genzyme and Teva.
TS has received honoraria from Actelion, Novartis, Sanofi Genzyme, Electrocore, Merck and Teva.
CP has served on scientific advisory boards for Novartis, Merck, Biogen, Sanofi, Genzyme, Teva, Actelion and funding for travel and speaker honoraria from Biogen, Teva, Sanofi Genzyme, Actelion and Novartis, and research support from Biogen, Teva, Novartis and Genzyme.
Abstract: P568
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Objectives: The POINT study aims to evaluate the safety and efficacy of ponesimod as add-on treatment to dimethyl fumarate (DMF) in patients with relapsing multiple sclerosis (RMS).
Introduction: Despite recent advances in the treatment of RMS, an unmet medical need remains to improve long-term disease control without compromising patient safety. Targeting RMS treatment with a combination of compounds that have different mechanisms of action may reduce disease activity to a level not achieved by any agent alone. Ponesimod, a novel, selective and rapidly reversible sphingosine-1-phosphate receptor modulator, has shown beneficial effects in a Phase 2 study and is currently in Phase 3 clinical development for RMS. Ponesimod acts by sequestering lymphocytes in lymphoid organs, thus reducing their circulation to the brain. DMF exhibits anti-inflammatory and potentially neuroprotective, anti-oxidative effects via inhibition of NF-κB and activation of Nrf-2. In preclinical studies, the combination of ponesimod with DMF showed improved efficacy versus each agent alone without increased toxicity. POINT is the first ever Phase 3 study in RMS where an oral investigational compound is added to oral background therapy approved for RMS.
Methods: Approximately 600 subjects with RMS who have signs of disease activity under ongoing treatment with DMF will be randomized 1:1 to ponesimod 20 mg or placebo as add-on treatment to DMF. Double-blind treatment will continue until the last subject enrolled has been treated for 60 weeks. Key eligibility criteria include a diagnosis of RMS, at least 6 months of ongoing treatment with DMF, stable lymphocyte counts above 800 cells/mm3, and documented clinical and/or MRI disease activity within 12-15 months of screening. The primary efficacy endpoint is the annualized relapse rate, defined as the number of confirmed relapses from randomization to the end of study. Other outcome measures include clinical and MRI disease activity, fatigue, as well as safety and tolerability. Details of the study design and study status will be presented.
Results: Enrolment began in February 2017 and is ongoing.
Conclusion: POINT, as the first Phase 3 study investigating the combination of two oral compounds with different modes of action addressing relevant targets in the pathogenesis of MS, will provide valuable information about possible additive or even synergistic efficacy and the safety of this new treatment concept for RMS.
Disclosure: LK's Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
EL, AL and BH are employees of Actelion Pharmaceuticals. BH holds stock in Johnson and Johnson, Novo Nordisk and Idorsia.
MF has received honoraria from Actelion, Bayer Healthcare, Biogen Idec, Chugai, Clene Nanomedicine, EMD Canada, Genzyme, Hoffman La-Roche, MedDay, Merck Serono, Novartis, Sanofi-Aventis, Teva Canada Innovation, and research support from Genzyme.
RF has received honoraria from Actelion, Biogen, Genentech, Idec, Novartis, Teva, and research support from Biogen and Novartis.
EH has received honoraria from Actelion, Biogen, Celgene, Merck, Novartis, Sanofi Genzyme and Teva.
RH has received honoraria from Actelion, Biogen, Genzyme-Sanofi, Novartis, Roche, and research support from Biogen, Genzyme-Sanofi, Novartis, Roche.
FL has received honoraria from Abbvie, Acorda, Actelion, Akros, Apitope, Atara Biotherapeutics, Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Forward Pharma, Innate Immunotherapeutics, Mapi Pharma, Medday, MedImmune, Novartis, Polpharma, Receptos/Celgene, Regeneron, Roche/Genentech, Sanofi/Genzyme, Teva, TG Therapeutics, Toyama, and research support from Biogen Idec, Celgene; Genzyme, NIH, NMSS, Novartis Pharmaceuticals Corp, Sanofi, Teva Neuroscience, Inc., Transparency Life Sciences.
XM has been a clinical trial steering committee member or participated in advisory boards with Actelion, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Oryzon, Roche, Sanofi-Genzyme and Teva.
TS has received honoraria from Actelion, Novartis, Sanofi Genzyme, Electrocore, Merck and Teva.
CP has served on scientific advisory boards for Novartis, Merck, Biogen, Sanofi, Genzyme, Teva, Actelion and funding for travel and speaker honoraria from Biogen, Teva, Sanofi Genzyme, Actelion and Novartis, and research support from Biogen, Teva, Novartis and Genzyme.