A Phase I, Single-site, Open-label, Partially Randomized Study to Evaluate the Relative Bioavailability and Pharmacokinetics of Evobrutinib Following Administration of Different Formulations in Healthy Participants

The purpose of this study is to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety and tolerability of evobrutinib after oral administration of immediate release (IR) and modified release (MR) formulations in healthy participants.

Start Date02 Feb 2022

Sponsor / Collaborator

Merck Healthcare KGaA

[+1]

NCT05248945 / CompletedPhase 1

Phase I, Open-Label, Single-Sequence Study of the Effect of Multiple Doses of Carbamazepine on Single-Dose Evobrutinib Pharmacokinetics in Healthy Participants

The purpose of this study is to investigate the effect of multiple doses of carbamazepine on two single doses of evobrutinib pharmacokinetics (PK) in healthy participants. Study details include:
Study Duration: up to 54 days. Treatment Duration: 25 days. Visit Frequency: Participants will be resident in the Clinical Research Unit from Day 1 to Day 20 and return on Day 26 for a Safety Follow-Up visit.

Start Date13 Jan 2022

Sponsor / Collaborator

Merck Healthcare KGaA

NCT05064488 / CompletedPhase 1

A Phase I, Open-Label, Two-Part Study of the Effect of Multiple-Dose Evobrutinib on Transporter Substrates Digoxin, Metformin, Rosuvastatin, and Sumatriptan Pharmacokinetics in Healthy Participants

This study consists of 2 parts: Part 1 and 2. The purpose of this study is to evaluate the pharmacokinetic, safety and tolerability of multiple doses of evobrutinib on single doses of digoxin, metformin and rosuvastatin in Part-1 and sumatriptan in Part-2 of the study.

Start Date04 Oct 2021

Sponsor / Collaborator

Merck Healthcare KGaA

100 Clinical Results associated with Evobrutinib

100 Translational Medicine associated with Evobrutinib

100 Patents (Medical) associated with Evobrutinib

Literatures (Medical) associated with Evobrutinib

01 Dec 2024·INTERNATIONAL IMMUNOPHARMACOLOGY

Bruton’s tyrosine kinase: A promising target for treating systemic lupus erythematosus

Review

Author: Zhou, Yu ; Sun, Lan ; Feng, Yifan ; Ding, Qiaoyi ; Zhang, Tiantai

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disorder involving multiple organs and systems. There is growing evidence that autoreactive B cells occupy a central role in the occurrence and progression of SLE due to their ability to generate pathogenic autoantibodies. Small molecule inhibitors targeting Bruton's tyrosine kinase (BTK), a crucial intracellular kinase regulating B cell development and function, emerge as a new strategy to treat SLE in recent years and are superior to biologic agents depleting B cells in many aspects. Supportive data obtained from lupus-prone mice preliminarily demonstrated the promising therapeutic potential of BTK inhibition. However, these BTK inhibitors, including elsubrutinib, evobrutinib, etc., mostly face with unsatisfactory efficacy and certain safety issues during clinical use, driving the quest for new-generation inhibitors with improved potency and higher selectivity. This paper elaborates the importance of BTK involvement in SLE pathogenesis, reviews the clinical research progress of BTK inhibitors for SLE and discusses limitations and challenges the drugs met in development, in order to contribute to a deeper understanding of disease mechanism and provide a reference for new-generation BTK inhibitor research.

01 Nov 2024·LANCET NEUROLOGY

Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials

Article

Author: Guehring, Hans ; Cross, Anne H ; Hyvert, Yann ; Stuve, Olaf ; Cree, Bruce A C ; Arnold, Douglas L ; Vermersch, Patrick ; Tomic, Davorka ; Le Bolay, Claire ; Gopalakrishnan, Sathej ; Shen Loo, Li ; Montalban, Xavier ; Javor, Andrija ; Kappos, Ludwig ; Tenenbaum, Nadia ; Kubala Havrdova, Eva ; Wolinsky, Jerry S ; Dahlke, Frank ; Bar-Or, Amit ; Wiendl, Heinz

BACKGROUND:

Evobrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has shown preliminary efficacy in people with relapsing multiple sclerosis in a phase 2 trial. Here, we aimed to compare the safety and efficacy of evobrutinib with the active comparator teriflunomide in people with relapsing multiple sclerosis.

METHODS:

EvolutionRMS1 and evolutionRMS2 were two multicentre, randomised, double-blind, double-dummy, active-controlled, phase 3 trials conducted at 701 multiple sclerosis centres and neurology clinics in 52 countries. Adults aged 18-55 years with relapsing multiple sclerosis (Expanded Disability Status Scale [EDSS] score of 0·0-5·5) were included. Participants were randomly assigned (1:1) using a central interactive web response system to receive either evobrutinib (45 mg twice per day with placebo once per day) or teriflunomide (14 mg once per day with placebo twice per day), all taken orally and in an unfasted state, with randomisation stratified by geographical region and baseline EDSS. All study staff and participants were masked to the study interventions. The primary endpoint for each study was annualised relapse rate based on adjudicated qualified relapses up to 156 weeks, assessed in the full analysis set (defined as all randomly assigned participants) with a negative binomial model. These studies are registered with ClinicalTrials.gov (NCT04338022 for evolutionRMS1 and NCT04338061 for evolutionRMS2, both are terminated).

FINDINGS:

The primary analysis was done using data for 2290 randomly assigned participants collected from June 12, 2020, to Oct 2, 2023. 1124 participants were included in the full analysis set in evolutionRMS1 (560 in the evobrutinib group and 564 in the teriflunomide group) and 1166 in evolutionRMS2 (583 in each group). 751 (66·8%) participants were female and 373 (33·1%) were male in evolutionRMS1, whereas 783 (67·2%) were female and 383 (32·8%) were male in evolutionRMS2. Annualised relapse rate was 0·15 (95% CI 0·12-0·18 with evobrutinib vs 0·14 [0·11-0·18] with teriflunomide (adjusted RR 1·02 [0·75-1·39]; p=0·55) in evolutionRMS1 and 0·11 (0·09-0·13 vs 0·11 [0·09-0·13]; adjusted RR 1·00 [0·74-1·35]; p=0·51) in evolutionRMS2. The pooled proportion of participants with any treatment-emergent adverse event (TEAE) was similar between treatment groups (976 [85·6%] of 1140 with evobrutinib vs 999 [87·2%] of 1146 with teriflunomide). The most frequently reported TEAEs were COVID-19 (223 [19·6%] with evobrutinib vs 223 [19·5%] with teriflunomide), alanine aminotransferase increased (173 [15·2%] vs 204 [17·8%]), aspartate aminotransferase increased (110 [9·6%] vs 131 [11·4%]), and headache (175 [15·4%] vs 176 [15·4%]). Serious TEAE incidence rates were higher with evobrutinib than teriflunomide (86 [7·5%] vs 64 [5·6%]). Liver enzyme elevations at least 5 × upper limit of normal were more common with evobrutinib than with teriflunomide, particularly in the first 12 weeks (55 [5·0%] vs nine [<1%]). Three people who received evobrutinib and one who received teriflunomide met the biochemical definition of Hy's law; all cases resolved after discontinuation of treatment. There were two deaths (one in each group), neither related to study treatment.

INTERPRETATION:

The efficacy of evobrutinib was not superior to that of teriflunomide. Together, efficacy and liver-related safety findings do not support the use of evobrutinib in people with relapsing multiple sclerosis.

FUNDING:

Merck.

01 Sep 2024·Brain pathology (Zurich, Switzerland)

The relation between BTK expression and iron accumulation of myeloid cells in multiple sclerosis

Article

Author: Hametner, Simon ; Berger, Thomas ; Riedl, Christian ; Lassmann, Hans ; Steinmaurer, Anja ; Wimmer, Isabella ; König, Theresa ; Testa, Giulia ; Köck, Ulrike ; Höftberger, Romana ; Bauer, Jan

Abstract:

Activation of Bruton's tyrosine kinase (BTK) has been shown to play a crucial role in the proinflammatory response of B cells and myeloid cells upon engagement with B cell, Fc, Toll‐like receptor, and distinct chemokine receptors. Previous reports suggest BTK actively contributes to the pathogenesis of multiple sclerosis (MS). The BTK inhibitor Evobrutinib has been shown to reduce the numbers of gadolinium‐enhancing lesions and relapses in relapsing–remitting MS patients. In vitro, BTK inhibition resulted in reduced phagocytic activity and modulated BTK‐dependent inflammatory signaling of microglia and macrophages. Here, we investigated the protein expression of BTK and CD68 as well as iron accumulation in postmortem control (n = 10) and MS (n = 23) brain tissue, focusing on microglia and macrophages. MS cases encompassed active, chronic active, and inactive lesions. BTK+ and iron+ cells positively correlated across all regions of interests and, along with CD68, revealed highest numbers in the center of active and at the rim of chronic active lesions. We then studied the effect of BTK inhibition in the human immortalized microglia‐like HMC3 cell line in vitro. In particular, we loaded HMC3 cells with iron‐dextran and subsequently administered the BTK inhibitor Evobrutinib. Iron treatment alone induced a proinflammatory phenotype and increased the expression of iron importers as well as the intracellular iron storage protein ferritin light chain (FTL). BTK inhibition of iron‐laden cells dampened the expression of microglia‐related inflammatory genes as well as iron‐importers, whereas the iron‐exporter ferroportin was upregulated. Our data suggest that BTK inhibition not only dampens the proinflammatory response but also reduces iron import and storage in activated microglia and macrophages with possible implications on microglial iron accumulation in chronic active lesions in MS.

News (Medical) associated with Evobrutinib

06 Sep 2024

·www.biospace.com

Roche and Sanofi MS Trials Show Potential, Challenges of Oral BTK Inhibitors

iStock, WhataWin Roche’s fenebrutinib this week scored a mid-stage win in relapsing multiple sclerosis, while Sanofi’s tolebrutinib met the primary endpoint in a Phase III trial for progressive MS but flopped in two late-stage relapsing MS studies. It was a big news week for multiple sclerosis clinical trial readouts involving oral BTK inhibitors, which leverage their small molecular structure to cross the blood-brain barrier. Roche was the outright winner while Sanofi announced mixed results. Sanofi’s tolebrutinib on Monday missed the primary efficacy endpoints in two Phase III studies, failing to significantly reduce annualized relapse rate (ARR) in patients with relapsing MS (RMS), while succeeding in a third late-stage trial showing that the BTK inhibitor significantly delayed disability progression in patients with a less common form of progressive MS. Still, according to GlobalData, tolebrutinib “stands out as being particularly promising” and is expected to generate sales of approximately $2.6 billion in 2030 across seven major markets—the U.S., France, Germany, Italy, Spain, U.K. and Japan. The data analytics firm predicted worldwide sales of fenebrutinib will only reach $810 million that same year. Jefferies analysts described positivity around tolebrutinib, saying in a note to investors that despite the “mixed news,” Sanofi’s drug “now appears a largely de-risked perhaps $1–2 billion opportunity.” Meanwhile, just two days after Sanofi’s announcement, Roche’s fenebrutinib scored a mid-stage win in RMS, demonstrating near-total elimination of disease activity. GlobalData said the BTK inhibitor “shines” with 96% of patients treated free of relapses at one year, with data from three ongoing Phase III trials expected by the end of next year. According to Spherix Global Insights, orally administered BTK inhibitors are “already established in oncology” with U.S. neurologists “eagerly” awaiting the drug class for MS. However, the market research firm contends that setbacks involving safety have created an environment of uncertainty. Liver Safety and Secondary Endpoints in Focus While the overall sentiment for BTK inhibitors for MS is positive, the safety pro these treatments remains a point of concern. Sanofi’s Phase III tolebrutinib studies were placed on partial clinical hold by the FDA in June 2022 after researchers found cases of drug-induced liver injury in some patients, while the regulator put Roche’s fenebrutinib under a partial clinical hold in December 2023 after two patients experienced elevated hepatic transaminase and bilirubin levels indicative of liver injury. According to Jefferies analysts, liver safety “will be a key focus” at the Sept. 20 presentations of Sanofi’s HERCULES and GEMINI 1 and 2 full results at the 40th Congress of European Committee for Treatment and Research in Multiple Sclerosis in Copenhagen, Denmark. Shiv Saidha, professor of neurology at Johns Hopkins University, said on a Jefferies call Thursday that another important aspect of these data will be the benefit across secondary endpoints, noting the failure last year of Merck KGaA’s BTK inhibitor evobrutinib to show benefit on these measures in MS before the German pharma decided in March 2024 to terminate its development. Although Sanofi’s Phase III GEMINI 1 and 2 trials did not demonstrate a reduction in ARR, GlobalData observed that pooled data from secondary endpoints suggested a significant delay in the onset of confirmed disability worsening, aligning with the positive confirmed disability progression findings from the late-stage HERCULES study, and “providing a measure of support for tolebrutinib’s potential efficacy.” Nevertheless, there appears to be a bit of a confidence problem in the wider drug class, Jefferies analysts noted. “Investor expectations have likely been notably lower after competitor Merck KGaA’s evobrutinib RMS failure.” So the question remains: Can orally administered BTK inhibitors ultimately succeed in MS like they have in oncology?

Phase 3Clinical Result

05 Sep 2024

·www.echemi.com

Roche Reveals Striking Data: 96% of Patients Did Not Relapse Within a Year, but Safety is in Doubt

Roche announced on September 4 the latest results from the Phase II FENopta Open Label Extension (OLE) study of the BTK inhibitor fenebrutinib. The results of the study showed that patients with relapsing multiple sclerosis (RMS) who received fenebrutinib for up to one year maintained extremely low levels of disease activity and did not experience disability progression. Roche plans to present the latest data from the FENopta-OLE study at the 40th session of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Fenebrutinib is an oral, reversible, non-covalently bound BTK inhibitor that can effectively block the function of BTK. Preclinical studies have shown that fenebrutinib has significant activity and is highly selective, being 130 times more selective to BTK than other kinases. Currently, fenebrutinib is the only reversible BTK inhibitor in Phase III trials for the treatment of multiple sclerosis. The FENopta study is a 12-week global, randomized, double-blind, placebo-controlled Phase II clinical trial designed to evaluate the efficacy, safety, and pharmacokinetics of fenebrutinib in 109 RMS patients aged 18 to 55 years. The primary endpoint was the number of new T1 lesions (T1-GD +) detected by brain magnetic resonance imaging (MRI) at weeks 4, 8, and 12, while secondary endpoints included the number of new/expanded T2 lesions detected by brain MRI at weeks 4, 8, and 12. And the proportion of patients with new T1-Gd+ lesions and new/enlarged T2 lesions at week 4, 8 and 12. T1 lesions are markers of active inflammation, while T2 lesions represent disease burden or lesion load. Data from the 12-week study showed that fenebrutinib significantly reduced the number of new T1 lesions and new/enlarged T2 lesions compared to the placebo group. Of the patients who completed the FENopta study, 99 chose to continue participating in the Open Label Extension (OLE) study to receive fenebrutinib for up to 192 weeks. During OLE, 96% of patients treated with fenebrutinib were disease free at one year, with an annualized recurrence rate (ARR) of 0.04, and disability remained stable at 48 weeks. MRI scans showed that fenebrutinib treatment effectively suppressed disease activity in the brain. At 48 weeks, 99% of patients had no T1-Gd+ lesions. Within 48 weeks of continued treatment with fenebrutinib, T2 lesion volume decreased by a factor of 3 compared to the end of the double-blind period (-0.33 cm3 vs -0.11 cm3). The safety profile of Fenebrutinib in OLE is consistent with previously reported data. The most common adverse events (aes) in more than 5% of patients included urinary tract infections (8%), COVID-19 (7%), and pharyngitis (5%). One patient (1%) had a serious adverse event. Another patient (1%) had an asymptomatic elevation of alanine aminotransferase (ALT), which returned to normal after discontinuation. There are currently three ongoing Phase III clinical trials of fenebrutinib, including the FENhance 1 and FENhance 2 studies in patients with RMS, and the FENtrepid study in patients with primary progressive multiple sclerosis (PPMS). Data from these studies are expected to be available by the end of 2025. Levi Garraway, MD, Roche's chief medical officer and head of global product development, said: "After one year of treatment, our BTK inhibitor fenebrutinib was able to effectively inhibit virtually all disease activity and disability progression in patients with multiple sclerosis. If these results are confirmed in the ongoing Phase III study, fenebrutinib is expected to further improve the treatment landscape for patients with multiple sclerosis." According to the information of the Medical Rubik's Cube database, a total of 4 BTK inhibitors are currently undergoing phase III clinical studies for multiple sclerosis in the world, and fenebrutinib is the only third-generation BTK inhibitor. The other three are evobrutinib (Merck), remibrutinib (Novartis) and tolebrutinib (Sanofi). In addition, there are three BTK inhibitors in Phase II clinical studies in multiple sclerosis, including obutinib (Norzenogenat), pitobutinib (Eli Lilly), and BIIB091 (Bogen).

Phase 2Clinical ResultPhase 3

03 Sep 2024

·www.biopharmadive.com

Sanofi finds a silver lining in mixed MS drug results

Dive Brief:An experimental Sanofi medicine failed two studies in multiple sclerosis but met its main objective in a third trial in a less common form of the disease, the company said Monday.In two Phase 3 studies of people with relapsing forms of MS, the drug tolebrutinib wasnt better than another Sanofi medicine, Aubagio, at reducing the rate of disease flare-ups. But tolebrutinib did meaningfully delay the onset of disability progression in people with non-relapsing secondary progressive MS in a separate late-stage trial, and showed a similar effect in the other two trials as well, Sanofi said.Sanofi only provided summary results. Specific data will be presented at a medical meeting later this month. But the company did say the findings will form the basis of discussions with drug regulators. A Phase 3 trial is also underway in primary progressive MS, for which success depends on tolebrutinibs ability to delay disability progression. Results are expected next year.Dive Insight:Analysts and investors have dialed back their expectations for tolebrutinib since Sanofi bought its developer, Principia Biopharma, four years ago.The drug is part of a newer generation of would-be MS medications called BTK inhibitors that, unlike their cancer-fighting predecessors, are designed to get into the brain and treat autoimmune conditions. However, study results so far have been underwhelming. Safety concerns slowed the progress of multiple programs, including tolebrutinib, while Merck KGaAs evobrutinib failed a pair of Phase 3 tests last December.Ahead of Sanofis readout, many investors anticipated negative tolebrutinib news, wrote Leerink Partners analyst David Risinger on Tuesday. Its studies in relapsing MS were designed similarly to Merck KGaAs trials and, even if the results had been positive, tolebrutinib would eventually have had to compete with several effective and convenient medicines, added Stifels Eric Le Berrigaud in a separate client note.Yet, by claiming success in non-relapsing secondary progressive MS, or nrSPMS, Sanofi may have a chance to make something of tolebrutinib. The condition is different from relapsing MS in that people accumulate disabilities over time, instead of experiencing periodic disease flares. There are also no therapies specifically approved to treat it, meaning tolebrutinib become a referenced drug for the disease, if not the standard of care, wrote Le Berrigaud. He estimates tolebrutinib still holds the potential to be a blockbuster medicine, with a market opportunity of about $3 billion to $3.5 billion in the U.S. alone.Even at that figure, tolebrutinibs sales potential would be lower than what Sanofi once envisioned. The company believes about 170,000 people are currently diagnosed with nrSPMS in the U.S. and Europe, far fewer than the 910,000 Sanofi has estimated to have relapsing MS.Additionally, Sanofi hasnt disclosed important information from the tolebrutinib trial, like how much the drug benefited patients or whether it caused liver-related side effects that have occurred in testing of BTK blockers for MS. A preliminary analysis of liver safety was consistent with previous tolebrutinib studies, Sanofi said in its statement.Leerinks Risinger also noted how, even if tolebrutinib is approved, insurers may limit access in nrSPMS and prioritize off-label use of other MS drugs since it couldnt outperform Aubagio.Further competition could be coming, too. Roche and Novartis have BTK inhibitors in advanced testing for MS, with results coming in the next couple of years, according to a federal database. '

Phase 3AcquisitionClinical Result

100 Deals associated with Evobrutinib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Rhabdomyosarcoma	Phase 3	US	Merck KGaA	10 Sep 2019
Rhabdomyosarcoma	Phase 3	DE	Merck KGaA	10 Sep 2019
Multiple sclerosis relapse	Phase 3	US	Merck KGaA	26 Aug 2019
Multiple sclerosis relapse	Phase 3	DE	Merck KGaA	26 Aug 2019
Multiple Sclerosis, Relapsing-Remitting	Phase 3	US	Merck KGaA	26 Aug 2019
Multiple Sclerosis, Relapsing-Remitting	Phase 3	DE	Merck KGaA	26 Aug 2019
Systemic Lupus Erythematosus	Phase 2	US	Merck KGaA	04 Jan 2017
Systemic Lupus Erythematosus	Phase 2	JP	Merck KGaA	04 Jan 2017
Systemic Lupus Erythematosus	Phase 2	AR	Merck KGaA	04 Jan 2017
Systemic Lupus Erythematosus	Phase 2	BG	Merck KGaA	04 Jan 2017

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04338061 \| NCT04338022 (evolutionRMS 1, Biospace) Manual	Phase 3	Multiple sclerosis relapse	-	Evobrutinib (evolutionRMS 1)	fnjeikmfps(oxqxnvakpv) = ublqxvnqgl evydlpskxl (olpoicbcpk ) Not Met	Negative	05 Dec 2023
				teriflunomide (evolutionRMS 1)	fnjeikmfps(oxqxnvakpv) = nercxcxqbb evydlpskxl (olpoicbcpk ) Not Met
NCT02975349 (Phase 2 OLE, ECTRIMS2023)	Phase 2	Bruton Type Agammaglobulinemia	267	Evobrutinib 25mg QD	udjvnmtswq(yckkjzznli) = Treatment-emergent adverse events (TEAEs) were reported by 142/164 PwRMS (86.6%) wedicpraqb (ihxhptszju ) View more	Positive	30 Sep 2023
				Evobrutinib 75mg BID
NCT02975349 (Phase II, EAN2023)	Phase 2	Rhabdomyosarcoma	45	Evobrutinib 75mg twice-daily	ggsnjbbwga(lztqpowqny) = dgeggbyaeg hskdfjeisd (hhwqktiqcg )	Positive	28 Jun 2023
ACTRIMS2023	Not Applicable	Neuroinflammation	-	Evobrutinib	txrhjfbqmb(autjsgpjfm) = dukmmfzfyl xnyyzsdmhk (myfaeenfbh )	Positive	30 May 2023
				Anti-CD20 (clone: SA271G2)	yewgeklbqg(bkqyonxita) = xkvjzhppzk ezctxyoeoe (qbxkhfnocf ) View more
ACTRIMS2023	Not Applicable	Multiple sclerosis relapse	-	Evobrutinib 75 mg twice-daily	ekhfhxxebw(jgxnwaltcz) = qexngqtzkc alxtnzonmr (xycursefqk, 4.5)	-	30 May 2023
				mRNA COVID-19 vaccine	ekhfhxxebw(jgxnwaltcz) = rdesjgelhq alxtnzonmr (xycursefqk, 4.3)
NCT02975349 (AAN2023)	Phase 2	Multiple sclerosis relapse	45	Evobrutinib 75mg twice-daily	epbfqxqvcm(mhrpubdeic) = pizijmiezh bmumsbtqtj (brkqgheuxe )	-	25 Apr 2023
				mRNA COVID-19 vaccine	epbfqxqvcm(mhrpubdeic) = bliehrwpoo bmumsbtqtj (brkqgheuxe )
AAN2023	Not Applicable	Neuroinflammation	-	Evobrutinib	cayhwbileb(pjfiqzvdss) = vnvfrnlrmm swszesjnlx (itnxhkssih ) View more	Positive	25 Apr 2023
NCT03233230 \| NCT02975349 \| NCT02975336 (Pubmed)	Phase 2	Multiple Sclerosis \| Rheumatoid Arthritis \| Systemic Lupus Erythematosus	1,083	Evobrutinib	izlmufcedu(wztjishhnf) = idqgchgosq ihdccaakal (bhndvyfdtc ) View more	-	23 Nov 2022
				Placebo	izlmufcedu(wztjishhnf) = beksjeqpcd ihdccaakal (bhndvyfdtc ) View more
NCT02975349 (ECTRIMS2022)	Phase 2	Multiple sclerosis relapse neurofilament light chain (NfL)	-	EVO 75mg BID	muqaxjrpqe(uvfjeqmcil) = dgpvgflfyv dxdfjxgerk (uuezunifjx, (30.0 - 79.0))	Positive	12 Oct 2022
				PBO/EVO 25mg QD	muqaxjrpqe(uvfjeqmcil) = aouehjpmgm dxdfjxgerk (uuezunifjx, (29.0 - 83.0))
NCT02975349 (ECTRIMS2022)	Phase 2	Multiple sclerosis relapse	267	Evobrutinib 75mg QD	vtndeqcjuy(gcqevydjwe) = rmgbpxqagf bzokaagrft (miytaicfnd )	-	12 Oct 2022
				Evobrutinib 75mg BID	vtndeqcjuy(gcqevydjwe) = euvqshghbt bzokaagrft (miytaicfnd )

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