Abstract Details

Title Lymphocyte Depletion and Repopulation Following Subcutaneous or Intravenous Alemtuzumab in Patients with Progressive Multiple Sclerosis: SCALA Study Results

Topic Multiple Sclerosis

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 332

Objective

Characterize the pharmacodynamic (PD) profile of subcutaneous (SC) or intravenous (IV) alemtuzumab in patients with progressive multiple sclerosis (PMS).

Background

In the phase 3 CARE-MS studies of relapsing-remitting MS patients, IV alemtuzumab resulted in selective depletion and a distinct pattern of repopulation of circulating CD52-expressing T and B lymphocytes, although clinical PD studies of SC alemtuzumab are needed.

Design/Methods Phase 1, 60-month exploratory, single-center, open-label, randomized, parallel group study in patients aged ≥18 years with primary/secondary PMS, comprising two 12-month study periods and a safety monitoring phase (SCALA; NCT02583594). Patients received alemtuzumab 12 mg/day either SC or IV on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Primary endpoint was change in CD3⁺ lymphocyte levels, and secondary endpoints included PD of other lymphocyte subpopulations and total lymphocytes, CD4⁺/CD8⁺ T-lymphocyte ratio, pharmacokinetics, and adverse events (AEs).

Results 24 patients were randomized to alemtuzumab SC (n=16) or IV (n=8); 21/24 patients completed the main 24-month study period (SC, n=15; IV, n=6). Baseline characteristics were similar between SC and IV groups; mean (SD) age was 47.9 ± 8.6 years and 54.2% were female. During both study periods, CD3⁺ lymphocyte counts decreased similarly in the SC and IV groups over the first 30 days post-administration, followed by partial repopulation until period end (Month 12 or 24). Depletion and subsequent repopulation of total lymphocytes, CD4⁺ and CD8⁺ T lymphocytes, and CD19⁺ B lymphocytes was also observed in both the SC and IV groups. CD4⁺/CD8⁺ T-lymphocyte ratio decreased to Month 3 and remained stable to Month 24. Alemtuzumab concentrations were lower after SC versus IV administration, with a bioavailability of 32%. No AEs leading to study discontinuation or death occurred.

Conclusions

PMS patients receiving SC or IV alemtuzumab showed similar lymphocyte depletion and repopulation patterns and a similar safety profile.

Authors/Disclosures
Breogan Rodriguez Acevedo, MD PRESENTER	The institution of Mr. Rodriguez Acevedo has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis.
Carlos Nos, MD	Dr. Nos has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffmann-La Roche Ltd..
Darren P. Baker, PhD (Sanofi Genzyme)	Dr. Baker has received personal compensation for serving as an employee of Sanofi. Dr. Baker has received stock or an ownership interest from Sanofi.
	No disclosure on file
	No disclosure on file
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia)	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.

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