2. Academic Validation
  3. [Efficacy and safety of divozilimab during 24-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-2]

[Efficacy and safety of divozilimab during 24-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-2]

  • Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(4):37-47. doi: 10.17116/jnevro202312304137.
A N Boyko 1 2,  V M Alifirova 3,  I G Lukashevich 4,  Z A Goncharova 5,  I V Greshnova 6,  L G Zaslavsky 7,  S V Kotov 8,  N A Malkova 9,  G N Mishin 10,  E V Parshina 11,  I Ye Poverennova 12,  L N Prakhova 13,  S A Sivertseva 14,  I V Smagina 15,  N A Totolyan 16,  Yu V Trinitatsky 17,  T N Trushnikova 18,  F A Khabirov 19,  S G Shchur 20,  A V Artemyeva 21,  D D Bolsun 21,  A V Zinkina-Orikhan 21,  Yu N Linkova 21
Affiliations

Affiliations

  • 1 Pirogov Russian National Research Medical University, Moscow, Russia.
  • 2 Federal Center of Brain and Neurotechnologies, Moscow, Russia.
  • 3 Siberian State Medical University, Tomsk, Russia.
  • 4 Orden of the Red Banner of Labor City Clinical Hospital No. 1, Chelyabinsk, Russia.
  • 5 Rostov State Medical University, Rostov-on-Don, Russia.
  • 6 Ulyanovsk Regional Clinical Hospital, Ulyanovsk, Russia.
  • 7 Leningrad Regional Clinical Hospital, St. Petersburg, Russia.
  • 8 Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia.
  • 9 State Novosibirsk Regional Clinical Hospital, Novosibirsk, Russia.
  • 10 Pyatigorsk City Clinical Hospital No. 2, Pyatigorsk, Russia.
  • 11 Semashko Nizhny Novgorod Regional Clinical Hospital, Nizhny Novgorod, Russia.
  • 12 Seredavin Samara Regional Clinical Hospital, Samara, Russia.
  • 13 N. Bechtereva Institute of the Human Brain, St. Petersburg, Russia.
  • 14 Medical and Sanitary unit «Neftyanik», Tyumen, Russia.
  • 15 Regional Clinical Hospital, Barnaul, Russia.
  • 16 Academician I.P. Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia.
  • 17 Rostov Regional Clinical Hospital, Rostov-on-Don, Russia.
  • 18 Wagner Perm State Medical University, Perm, Russia.
  • 19 Republican Clinical Nerological Center, Kazan, Russia.
  • 20 Municipal Filatov Clinical Hospital No. 15, Moscow, Russia.
  • 21 AO BIOCAD, St. Petersburg, Russia.
PMID: 37084363 DOI: 10.17116/jnevro202312304137
Abstract

Objective: To find the optimal therapeutic dose of the anti-B cell mAb divozilimab (DIV) based on the efficacy and safety data of intravenous administration at a dose of 125 mg or 500 mg in patients with relapsing remitting multiple sclerosis (RRMS) compared to placebo (PBO) and teriflunomide (TRF). To study the efficacy and safety of DIV within 24 weeks of treatment.

Material and methods: A multicenter, randomized, double-blind and double-masked, placebo-controlled phase 2 clinical trial (CT) BCD-132-2 involved 271 adult patients with RRMS from 25 centres In Russia. Patients were randomly assigned (2:2:2:1) into 4 groups: TRF, DIV 125 mg, DIV 500 mg and PBO. After screening patients entered to the main period, which consisted of one cycle of therapy for 24 weeks. The primary endpoint was the total number of gadolinium-enhancing T1 lesions (Gd+) observed on brain MRI scans after 24 weeks (per scan - involves estimating the mean value of the score from all the MRI assessments performed for each participant in the study).

Results: 263 patients completed 24 weeks of treatment. Most of the patients in the DIV groups had no lesions on T1-weighted MRI after 24 weeks of treatment (94.44% on 125 mg and 93.06% on 500 mg). In the TRF and PBO groups the values were significantly lower: 68.06% and 56.36% respectively (both p<0.05). The proportions of relapse-free patients in the DIV groups were 93.06% and 97.22% (125 mg and 500 mg, respectively). As expected, DIV reduced the CD19+ B-cells. However, the repopulation rate of CD19+ B-cells in the 125 mg group was more pronounced (mainly due to the recovering pool of CD27-naive B-cells) compared to the 500 mg group. DIV showed a favorable safety profile at both doses.

Conclusion: Thus, the assessment of 24 weeks treatment demonstrated that DIV is a highly effective, safe and convenient option for the treatment of RRMS patients, both naive and previously treated with disease modifying therapy. A dose of 500 mg is recommended for further efficacy and safety evaluation during phase 3 CT.

Keywords

B-lymphocytes; CD19+ B-cells; CD20+ B-cells; anti-CD20 monoclonal antibody; divozilimab; multiple sclerosis.

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