Abstract Details

Title Oral Cladribine as Add on to IFN ? Therapy in Patients with Active Multiple Sclerosis: Results from the Phase II ONWARD Study

Topic MS and Related Diseases

Presentation(s) P07 - (-)

Poster/Presentation
Number 099

Objective

Background BACKGROUND: This study was the first evaluation of safety and tolerability of cladribine as potential add-on therapy in the treatment of MS patients experiencing active disease despite treatment with IFN-?. The 96-week double-blind period was complete when the cladribine development program was stopped; safety and exploratory efficacy results from this core part of the trial are presented.

Design/Methods DESIGN/METHODS: Patients aged 18-65 years with active MS were randomized to receive either 3.5mg/kg cladribine or placebo, both added on to IFN ? therapy during the 96-week double-blind period(DBP). Safety endpoints included adverse events(AEs) and laboratory parameters. Relapses are also presented.

Results RESULTS: 172 patients were randomized in the DBP and received 3.5mg/kg cladribine (n=124) or placebo (n=48), added-on to IFN ?. Overall incidences of AEs and SAEs were comparable between treatment groups, with the exception of lymphopenia. A greater proportion of cladribine add-on patients (63.7%) experienced CTCAE Grade 3-4 lymphopenia, as compared to placebo add-on patients (2.1%). There was a slightly higher incidence of infections in cladribine-treated group vs. placebo (61.3% vs. 54.2%). Four infections were SAEs (all in cladribine-treated patients), and no unexpected opportunistic infections were reported. One patient developed a malignancy during the study: squamous cell carcinoma, 2.35 years after first cladribine exposure. The patient's risk factor included a 25-year smoking history. Patients receiving cladribine add-on were 62% less likely to have a qualifying relapse, as compared to patients receiving placebo add-on.

Conclusions CONCLUSIONS: No new or unexpected safety issues were found. The combination therapy appeared effective; however efficacy analyses were not powered. An excess of grade 3 lymphopenia, compared with that reported in previous cladribine studies was observed which may be partly attributable to the concomitant administration of IFN-?.

Authors/Disclosures
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia) PRESENTER	The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS/ Celgene. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/ Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIAL PD. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerVoice. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung Biosys. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion/ Janssen Pharmaceuticals. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS/ Celgene. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/ EMD Serono. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic Therapeutics. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris/ Mylan. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi/ Genzyme. The institution of Dr. Montalban has received research support from Merck/ EMD Serono. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva Pharmaceuticals. The institution of Dr. Montalban has received research support from Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received research support from BMS/ Celgene.
Bruce A. Cohen, MD, FAAN (Northwestern University, Feinberg School of Medicine)	Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. The institution of Dr. Cohen has received research support from Genentech. The institution of Dr. Cohen has received research support from MedDay. The institution of Dr. Cohen has received research support from Consortium of Multiple Sclerosis Centers.
Thomas Leist, MD, PhD, FAAN (Thomas Jefferson University)	Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Leist has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Leist has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Horizon. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Seono. Dr. Leist has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Wittness with DHHS HRSA.
Harold Moses, MD (Vanderbilt Multiple Sclerosis Center)	No disclosure on file
	No disclosure on file
	No disclosure on file
Matthew Scaramozza	Mr. Scaramozza has received personal compensation for serving as an employee of Biogen. Mr. Scaramozza has stock in Biogen. Mr. Scaramozza has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file

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