Challenges for Morocco's Economy after Covid-19, between Necessary Reforms and Maintaining Political Stability

Morocco has implemented various economic policies during the last decades. If the level of growth and the modernization seems relevant, the social programs were not efficient against poverty. During and now after the pandemic, an acceleration of the reforms seems to be considered by the authorities. This paper will analyze what was done and what the main challenges are for this country. © 2022 Geo Publishing, Toronto Canada.

Immune response following mRNA COVID-19 vaccination in patients with multiple sclerosis treated with the Bruton's tyrosine kinase inhibitor evobrutinib

Introduction: Evobrutinib is a highly selective, covalent Bruton's tyrosine kinase inhibitor (BTKi) being investigated for the treatment of relapsing multiple sclerosis (RMS). Previous analysis showed that patients with systemic lupus erythematosus receiving evobrutinib could mount a humoral response to seasonal influenza vaccination. However, the effects of BTKi on vaccine response in patients with MS are presently unknown. Objective(s): To examine the humoral response to mRNA COVID-19 vaccination in patients with RMS (PwRMS) receiving evobrutinib during the open-label extension (OLE) of a Phase II trial (NCT02975349). Method(s): A post hoc analysis of PwRMS who received evobrutinib 75 mg twice-daily and two doses of mRNA COVID-19 vaccination during the OLE (n=24). Immunoglobulin G (IgG) anti-S1 and anti-S2 specific antibodies to COVID-19 were measured using an indirect chemiluminescence immunoassay (DiaSorin Molecular LLC, USA;lower limit of quantification, 3.8 AU/mL;seronegative <15.0 AU/mL [n=19], seropositive >=15 AU/mL [n=5]). Result(s): Baseline mean (+/-SD) age of patients in the analysis was 44.6 (+/-10.1), 79.2% were female and mean/minimum evobrutinib exposure pre-vaccination was 105.8/97.6 weeks. All but one of the evobrutinib-treated patients developed or increased S1/S2 IgG antibody levels after two doses of mRNA vaccine (geometric mean [SD] pre-/post-vaccination: 6.7 [2.6]/209.1 [3.6] AU/mL;median pre-/post-vaccination: 3.8/185.0 AU/mL). Patients who were either S1/S2 IgG seronegative or seropositive pre-vaccination demonstrated a strong antibody response following vaccination (seronegative pre-/post-vaccination median: 3.8/167.0 AU/ mL;seropositive pre-/post-vaccination median: 26.2/715.0 AU/ mL). The majority of patients (n=22), whether seronegative or positive, had at least a 10-60-fold induction of S1/S2 IgG antibody levels from pre-to post-vaccination (median fold change of S1/S2 IgG antibody levels for total/seronegative/seropositive patients: 32.6/34.2/18.3). Conclusion(s): PwRMS treated with evobrutinib were able to mount an antibody response to two doses of mRNA COVID-19 vaccination. The marked increase in antibody response in seronegative and seropositive patients demonstrates a preserved response to novel and recall antigens in PwRMS undergoing BTKi with evobrutinib. This demonstration of a strong humoral response to vaccination during evobrutinib treatment is the first such evidence for any BTKi under investigation for the treatment of MS.

Safety/efficacy of evobrutinib, a Bruton's tyrosine kinase inhibitor, 2.5 years into Phase II MS open-label extension

Background and aims: Evobrutinib, a Bruton's tyrosine kinase inhibitor, was well tolerated and effective in a double-blind, randomised Phase II trial in patients with relapsing multiple sclerosis (pwRMS;NCT02975349). Objective: report evobrutinib safety and efficacy data 2.5 years into an open-label extension (OLE). Methods: In the 48-week (W) double-blind period (DBP), pwRMS (n=267) received placebo (switched to evobrutinib 25mg once-daily, W24), evobrutinib 25mg once-daily, 75mg once-daily, or 75mg twice-daily, or open-label dimethyl fumarate (DMF;240mg twice-daily). At W48 patients could enter the OLE (DMF: 4-8W washout);evobrutinib 75mg once-daily (median ∼48W) then 75mg twice-daily. We report the latest available OLE data. Results: Of 267 DBP patients, 213 (80%) entered the OLE;164 (61%) completed ≥132W OLE treatment. Treatmentemergent adverse events (TEAEs) were reported by 165/213 patients (77.5%);59 (27.7%) had a treatment-related TEAE (six were serious;Table). Severe/opportunistic infections (≥Grade 3) were reported by 9/213 patients (4.2%);three (not treatment related;Covid pneumonia [n=2]) were fatal. Most patients had normal IgG (91%), IgA (88%) and IgM (82%) levels (OLE W120). Mean CD19+ B cells levels were 0.218x106cells/mL (OLE baseline) and 0.122x106cells/ mL (OLE W96). ALT/AST elevations only occurred in patients previously receiving DMF/evobrutinib 25mg, and within 12W of OLE initiation. Amylase/lipase increases occurred in 6 (2.8%)/24 (11.3%) patients, without clinical signs and symptoms. ARR, for patients receiving 75mg twice-daily in the DBP, was 0.12 (95%CI 0.07-0.20 [all available OLE data]). Conclusion: Evobrutinib safety and efficacy data over 2.5 years shows acceptable tolerability, no new safety signals and maintained efficacy in pwRMS.

Safety and Efficacy of Evobrutinib, a Bruton's Tyrosine Kinase Inhibitorin Relapsing Multiple Sclerosis Over 2.5 Years of The Open-Label Extension to a Phase II Trial

Objective: Report the safety and efficacy of evobrutinib over 2.5 years in an open-label extension (OLE). Background: Evobrutinib, a covalent, blood-brain barrier-penetrating Bruton's tyrosine kinase inhibitor, was well tolerated and effective at reducing gadolinium-enhancing lesions in a double-blind, randomized phase II trial in patients with relapsing multiple sclerosis (pwRMS;NCT02975349). Design/Methods: In the 48-week (W) double-blind period (DBP), pwRMS (n=267) received placebo (switched to evobrutinib 25mg once-daily at W24), evobrutinib 25mg once-daily, 75mg once-daily, or 75mg twice-daily, or open-label dimethyl fumarate (DMF;240mg twice-daily). At W48 patients could enter the OLE (DMF: 4-8W washout);evobrutinib 75mg once-daily (median ~48W) then 75mg twice-daily. The latest available OLE data are now reported. Results: Of 267 DBP patients, 213 (80%) entered the OLE;164 (61%) completed ≥132W of OLE treatment. Treatment-emergent adverse events (TEAEs) were reported by 165/213 patients (77.5%);59 (27.7%) had a treatment-related TEAE. Six serious TEAEs were deemed treatment-related. Severe/opportunistic infections (≥Grade 3) were reported by 9/213 patients (4.2%);3 were fatal (Covid-19 pneumonia [n=2] and E. coli sepsis [n=1];not considered treatment-related). At OLE W120, most patients had IgG (91%), IgA (88%) and IgM (82%) within normal ranges. Overall mean CD19+ B cells levels were 0.218×10 cells/mL (OLE baseline) and 0.122×10 cells/mL (OLE W96). ALT/AST elevations were observed only in patients previously receiving DMF/evobrutinib 25mg and occurred within 12W of OLE initiation. Amylase/lipase increases occurred in 6 (2.8%)/24 (11.3%) patients, but without clinical signs and symptoms. Based on all available OLE data, ARR was 0.12 (95%CI 0.07-0.20) for patients receiving 75mg twice-daily in the DBP. 6 6 Conclusions: Evobrutinib safety and efficacy data over 2.5 years in pwRMS continue to show acceptable tolerability, with no new safety signals, and maintained efficacy.