Patient Preference for Subcutaneous Versus Intravenous Administration with Every-6-Week Natalizumab (Tysabri^®) Dosing: NOVA Phase IIIb Extension Study (Part 2)

Heinz Wiendl¹, John Foley², Gilles Defer³, Lana Zhovtis Ryerson⁴, Jeffrey A Cohen⁵, Douglas L Arnold⁶, Helmut Butzkueven⁷, Gary R Cutter⁸, Gavin Giovannoni⁹, Joep Killestein¹⁰, Rose Domingo-Horne¹¹, Marie Toukam¹¹, Aimie Nunn¹², Amir-Hadi Maghzi¹¹, Robert Kuhelj¹³, Tyler Lasky¹¹

Affiliations

¹ Department of Neurology with Institute of Translational Neurology, University of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. heinz.wiendl@ukmuenster.de.
² Rocky Mountain MS Clinic, Salt Lake City, UT, USA.
³ Centre Hospitalier Universitaire de Caen, Caen, France.
⁴ Hackensack Meridian Health Jersey Shore University Medical Center, Neptune City, NJ, USA.
⁵ Cleveland Clinic, Cleveland, OH, USA.
⁶ Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
⁷ Central Clinic School, Monash University, Melbourne, Australia.
⁸ University of Alabama, Birmingham, AL, USA.
⁹ Blizard Institute, London, UK.
¹⁰ MS Centre Amsterdam, Amsterdam, The Netherlands.
¹¹ Biogen, Cambridge, MA, USA.
¹² Cytel, London, UK.
¹³ , Biogen, Baar, Switzerland.

PMID: 39046635
PMCID: PMC11393236
DOI: 10.1007/s40120-024-00647-0

Patient Preference for Subcutaneous Versus Intravenous Administration with Every-6-Week Natalizumab (Tysabri^®) Dosing: NOVA Phase IIIb Extension Study (Part 2)

Heinz Wiendl et al. Neurol Ther. 2024 Oct.

. 2024 Oct;13(5):1385-1401.

doi: 10.1007/s40120-024-00647-0. Epub 2024 Jul 24.

Authors

Affiliations

¹ Department of Neurology with Institute of Translational Neurology, University of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. heinz.wiendl@ukmuenster.de.
² Rocky Mountain MS Clinic, Salt Lake City, UT, USA.
³ Centre Hospitalier Universitaire de Caen, Caen, France.
⁴ Hackensack Meridian Health Jersey Shore University Medical Center, Neptune City, NJ, USA.
⁵ Cleveland Clinic, Cleveland, OH, USA.
⁶ Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
⁷ Central Clinic School, Monash University, Melbourne, Australia.
⁸ University of Alabama, Birmingham, AL, USA.
⁹ Blizard Institute, London, UK.
¹⁰ MS Centre Amsterdam, Amsterdam, The Netherlands.
¹¹ Biogen, Cambridge, MA, USA.
¹² Cytel, London, UK.
¹³ , Biogen, Baar, Switzerland.

PMID: 39046635
PMCID: PMC11393236
DOI: 10.1007/s40120-024-00647-0

Abstract

Introduction: Following NOVA (part 1) and the approval of the subcutaneous (SC) route of administration of natalizumab by the European Medicines Agency, an extension phase of the NOVA phase IIIb study (part 2) was initiated to collect patient preference data for SC versus intravenous (IV) dosing in patients receiving every-6-week (Q6W) dosing of natalizumab. This study was performed to evaluate patient preference for SC versus IV natalizumab administration and explore the efficacy, safety, and pharmacology characteristics of both routes of administration.

Methods: In part 2, participants received natalizumab (Tysabri^®) 300 mg via IV infusion Q6W for 36 weeks and then were randomized to 48 weeks of crossover treatment (24 weeks SC Q6W and 24 weeks IV Q6W, or vice versa). The primary endpoint was the proportion of participants who indicated a preference for natalizumab SC administration on the Patient Preference Questionnaire.

Results: A total of 153 participants were randomized in NOVA part 2. Of 123 with patient preference data, 108 (87.8%) preferred the SC route of administration for natalizumab over the IV route; 102 (82.9%) specified "requires less time in the clinic" as the reason for the SC preference.

Conclusion: In NOVA (part 2), most participants on Q6W dosing of natalizumab preferred SC administration versus IV administration.

Clinicaltrials: GOV: NCT03689972. INFOGRAPHIC.

Keywords: Extended interval dosing; Intravenous; Multiple sclerosis; NOVA; Natalizumab; Patient preference; Subcutaneous.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Heinz Wiendl has received honoraria for consulting or speaking from AbbVie, Actelion, Alexion, Argenx, Biogen, Bristol Myers Squibb, Cognomed, EMD Serono, Evgen, F. Hoffmann-La Roche, Idorsia, IGES, Immunic, Immunovant, Janssen, Johnson & Johnson, MedDay, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva Pharmaceuticals, and UCB Pharma. John Foley has received speakers’ and consultant honoraria from Biogen, EMD Serono, Genentech, Genzyme, and Novartis. Gilles Defer has received personal compensation for scientific advisory boards or speaker honoraria from Biogen, Bristol Myers Squibb, Merck Serono, Novartis, Sanofi Genzyme, and Teva Pharmaceuticals. Lana Zhovtis Ryerson has received personal compensation for advisory board activities from Biogen, Genentech, and Novartis; and research support from Biogen, Celgene, and Genentech. Jeffrey A. Cohen has received personal compensation for consulting from Biogen, Bristol Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI, and for serving as an editor of Multiple Sclerosis Journal. Douglas L. Arnold has received consulting fees from Albert Charitable Trust, Alexion Pharma, Biogen, Celgene, Frequency Therapeutics, Genentech, Med-Ex Learning, Merck, Novartis, Population Council, Receptos, Roche, and Sanofi Aventis; and equity interest in NeuroRx. Helmut Butzkueven has received compensation for advisory board membership or speaker bureaus from Biogen, Merck, Novartis, Roche, and UCB Pharma; and honorarium for serving on the NOVA trial steering committee. Gary R. Cutter has participated on consulting or advisory boards for Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein Buendel, MedDay, MedImmune, Neurogenesis, Novartis, Osmotica, Perception Neurosciences, Recursion-Cerexis, Rekover, Roche, and TG Therapeutics. Gavin Giovannoni has received consulting or speaker fees from AbbVie, Aslan, Atara Biotherapeutics, Biogen, Bristol Myers Squibb–Celgene, GlaxoSmithKline, GW Pharma, Janssen-Actelion, Jazz Pharmaceuticals, LIFNano, Merck KGaA-EMD Serono, Novartis, Roche-Genentech, Sanofi Genzyme, and Teva Pharmaceuticals. Joep Killestein has received speaker and consulting fees from Biogen, Genzyme, Merck Serono, Novartis, Roche, and Teva Pharmaceuticals. Aimie Nunn is an employee of Cytel. Rose Domingo-Horne, Marie Toukam, Amir-Hadi Maghzi, Robert Kuhelj, Tyler Lasky are employees of and hold stock/stock options in Biogen.

Figures

**Fig. 1**
NOVA part 2 study design. IV intravenous, *Q4W* every 4 weeks dosing, *Q6W* every 6 weeks dosing, SC subcutaneous

**Fig. 2**
Proportion of participants indicating preference for SC administration of natalizumab in part 2. IV intravenous, *IV/SC* crossover from IV to SC, SC subcutaneous, *SC/IV* crossover from SC to IV

**Fig. 3**
Mean (± SE) serum trough natalizumab concentration over time in A PK population and mean value of trough α4 integrin saturation (on MNC) over time in B PD population. IV intravenous, *MNC* mononuclear cells, PD pharmacodynamic, PK pharmacokinetic, SC subcutaneous, *IV/SC* crossover from IV to SC, *SC/IV* crossover from SC to IV, SE standard error. PK population: all participants who received one or more doses of SC or IV natalizumab and had one or more post-baseline concentration of natalizumab in serum. PD population: all participants who received one or more dose of SC or IV natalizumab after randomization in part 2 and have one or more post-baseline assessment of the PD parameter. Week 0: the last value taken prior to the first dose of the crossover period. The dotted lines represent the randomization visit and the beginning of period 2, respectively

See this image and copyright information in PMC

References

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Patient Preference for Subcutaneous Versus Intravenous Administration with Every-6-Week Natalizumab (Tysabri^®) Dosing: NOVA Phase IIIb Extension Study (Part 2)

Affiliations

Patient Preference for Subcutaneous Versus Intravenous Administration with Every-6-Week Natalizumab (Tysabri^®) Dosing: NOVA Phase IIIb Extension Study (Part 2)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Associated data

LinkOut - more resources

Full Text Sources

Medical