New developments in the field of Roche's rare neurological diseases

Neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD), etc.
all belong to the category of rare diseases, but doctors and related pharmaceutical companies have not stopped Research and exploration of these diseases
.

At this AAN conference, Roche's therapeutic drug Satralizumab (available on the market) for NMOSD, Ocrelizumab for MS, and Risdiplam for SMA ( There are new research progresses on the drug SRP-9001 for DMD, let Xiaobian take you to see the latest research results! Two previous double-blind (DBP) phase 3 studies (SAkuraSky study (saterilizumab combined with immunosuppressants) of the long-term efficacy of satrilizumab in the treatment of aquaporin-4-IgG positive neuromyelitis optica spectrum disorder) and SAkuraStar study (saterilizumab monotherapy)) found that saterilizumab significantly reduced the risk of relapse (protocol-defined relapse PDR) in patients with neuromyelitis optica spectrum disorder (NMOSD) compared with placebo
.

Based on this, we conducted an open-label extension phase (OLE) study that included 111 aquaporin-4-IgG patients who participated in these two DBP studies and received long-term satrilizumab 120 mg, Q4w.
In patients with positive NMOSD (SAkuraSky: 49; SAkuraStar: 62), the long-term efficacy of satrilizumab was further evaluated
.

Measures of efficacy included: protocol-defined relapse (iPDR), severe iPDR, and sustained worsening on the Extended Disability Status Scale (EDSS)
.

 Long-term results from this open-label extension study showed that over 3.
7 years of treatment, there was no recurrence of iPDR (71% and 73%, Figure 1), no severe recurrence of iPDR (91% and 90%, Figure 2), The proportion of patients with no persistent deterioration of EDSS scores (90% and 86%, Figure 3) was high, the annual mean ARR was consistently low (0.
12 and 0.
08), and the highest ARR level did not exceed 0.
20 (0.
02) at the end of the 1st to 4th year of treatment.
~0.
20), and no new safety risks emerged (up to 7 years of treatment)
.

Fig.
1iPDR situationFig.
2 Severe iPDR situationFig.
3 EDSS score deterioration Long-term Efficacy of Satralizumab in Aquaporin-4-IgG-seropositive Neuromyelitis Optica Spectrum Disorder (NMOSD): Results from the Open-label Extension Periods of SAkuraSky and SAkuraStar (full text access) Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis who have suboptimal responses to disease-modifying therapy - 3-year data from CASTING and LIBERTO (LIBERTO 1-year interim results) Efficacy and safety in patients with relapsing-remitting multiple sclerosis ≥6 months on 1-2 disease-modifying therapies (DMTs), found that most patients had no evidence of disease activity for at least 2 years after receiving ocrelizumab, but Long-term efficacy data are lacking
.

Based on this, the researchers continued to include some patients for a long-term extension study after the CASTING study to evaluate the long-term efficacy and safety of ocrelizumab
.

The LIBERTO study included patients with a positive benefit-risk ratio in the CASTING study who continued to receive ocrelizumab 600 mg Q24w (Figure 4), with efficacy endpoints of no evidence of disease activity (no protocol-defined relapse (NEDA), 24-week disability progression, Contrast-enhanced T1-weighted lesions and new/enlarged T2-weighted lesions) and redefined baseline MRI at week 8 of the CASTING study, with safety outcomes including incidence and nature of adverse events
.

Figure 4 Study design of the CASTING study and the LIBERTO study The study found that most patients were NEDA-free (either clinical or radiographic evidence) in each year over the course of 3 years of treatment (Figure 5)
.

Overall, 59.
4% of patients were NEDA-free within 3 years of treatment, 68.
1% had no evidence of clinical activity, and 86.
6% had no evidence of radiographic activity
.

Figure 5 NEDA Situation Study During 3 years of treatment, the EDSS score, annual recurrence rate, and MRI imaging examinations were all at a stable level with minimal changes (Figure 6)
.

Figure 6 Changes of each evaluation index during 3 years of treatment In terms of safety, although 92.
3% (405/439) of patients experienced adverse events (Figure 7), most of them were mild or moderate AEs, and 8.
4% (37/439) patients experienced SAE
.

During the entire study, no new safety incidents emerged
.

Figure 7 Major AEs Overall, based on clinical manifestations and imaging findings, for patients who have received 1-2 DMTs with suboptimal efficacy, after switching to ocrelizumab treatment, the efficacy is stable and satisfactory for at least 3 years of treatment and ongoing, with no new security incidents
.

 Efficac and Safety of Ocrelizumab in Patients With RRMS With Suboptimal Response to Prior Disease-Modifying Therapies: 3-Year Data From CASTING and LIBERTO (LIBER TO 1-Year Interim Results) (full text access) SUNFISH: risdiplam therapy 3-Year Efficacy and Safety of Type 2/3 SMA Risprom is an oral, survival motor neuron 2 (SMN2) splicing modifier approved by the FDA and CDE for the treatment of 2 months of age and older patients with spinal muscular atrophy (SMA)
.

Its pivotal study, the SUNFISH study, was a randomized, double-blind, global, multicenter, placebo-controlled study in 2-25-year-old patients with type 2/3 SMA.
The study was divided into two parts
.

Part 1 (N=51) evaluated the safety, tolerability and pharmacokinetics/pharmacodynamics of risprom at different dose levels in type 2 and type 3 SMA
.

Part 2 (N=180) evaluated the efficacy and safety of risprom at doses selected in part 1 relative to placebo in type 2 and ambulatory type 3 SMA
.

In Part 2, subjects continued on risprom through month 24 after 12 months of treatment with either risprom or placebo
.

After the completion of the 24-month study in Part 2, an open-label extension period may be entered
.

The study noted that in SUNFISH Part 2, 95% of patients received Risprom for more than 3 years, and only 5% (9/180) of patients did not complete the 3-year treatment
.

In terms of treatment effect, compared with baseline, the MFM32 (Motor Function Assessment Scale 32) total score of SMA patients maintained an increase from 12 months to 36 months of risprom treatment; while untreated patients with natural history The overall MFM32 score showed a downward trend
.

(Fig.
8) Fig.
8.
Changes in MFM32 score of SUNFISH study part 2 and natural history study (NatHis-SMA study) Proportion of patients with increased or stable MFM32 total score at 12 and 36 months of risprom treatment similar
.

(Fig.
9) Fig.
9.
The proportion of changes in MFM32 total score from baseline period.
From the 12th month to the 36th month of risprom treatment, the patients' RULM (Revised Upper Limb Function Module) and HFMSE (Hammersmith Motor Function Scale Extended) total Scores continued to rise; RULM and HFMSE total scores decreased over time in untreated patients with natural history
.

(Figure 10) Figure 10 Changes in RULM Score and HFMSE Score After 36 months of risprom treatment, the total SMAIS-ULM score reported by patients and their caregivers remained stable or improved from baseline
.

(Fig.
11) Fig.
11 SMAIS-ULM score changes In terms of safety, the incidence of AE also decreased with the prolongation of treatment time (Fig.
12).
The observed adverse events were mainly related to the primary disease, and there were no treatment-related AEs Conditions that led to discontinuation, no retinopathy found in animal studies, blood parameters remained stable, and no skin lesions
.

Figure 12 Changes in the incidence of AE and SAE during treatment This study confirmed that the treatment of risprom can significantly improve the motor function of SMA patients, improve the independence of patients, and the overall safety is good
.

 SUNFISH: 3-year Efficacy and Safety of Risdiplam in Types 2 and 3 SMA (full text access) RAINBOWFISH: Efficacy and safety of risdiplam in infants with presymptomatic SMA Risdiplam is currently FDA-approved For the treatment of spinal muscular atrophy (SMA) in patients 2 months of age and older, can it also be effective in children with presymptomatic SMA? This study initially explored the efficacy, safety, and pharmacokinetics/pharmacodynamics of risprom in the treatment of presymptomatic SMA infants
.

The RAINBOWFISH study is an open-label, single-arm, global multicenter study of genetically diagnosed children with presymptomatic SMA (regardless of SMN2 copy number) from birth to 6 weeks of age (first dose)
.

At 12 months, a preliminary analysis will be performed on children with 2 copies of SMN2 at baseline and a CMAP (compound muscle action potential) amplitude ≥1.
5 mV
.

The primary endpoint was the proportion of children with SMA who sat unsupported for ≥5 seconds.
Secondary endpoints included progression of SMA symptoms, survival, permanent ventilation, achievement of motor milestones, growth indicators, nutritional status, CMAP, pharmacokinetics and Security monitoring
.

Efficacy analysis of seven infants who had been treated with rispromum for more than 12 months found that these patients reached CHOP-INTEND (Children's Hospital of Philadelphia Infants with Neuromuscular Disease) at 4-5 months of age.
test) (Figure 13), maintained swallowing ability, and was able to feed orally
.

Figure 13 CHOP-INTEND scores Most children with 2 copies of SMN2 reached the WHO-specified healthy child motor milestones after ≥12 months of treatment
.

(Fig.
14) Fig.
14.
Motor milestones of children with 2 copies of SMN2 after treatment Most of the children with more than 2 copies of SMN2 reached the WHO-defined motor milestones for healthy children after ≥12 months of treatment
.

(Figure 15) Figure 15 Motor milestones after treatment in patients with more than 2 copies of SMN2 In terms of safety, the study analyzed all enrolled children (n=18).
, mostly related to age, and no drug-related ocular and skin symptoms, and blood parameters remained stable
.

No SAE was found either
.

In conclusion, risprom is also effective and safe for SMA patients <2 months of age
.

In the future, the RAINBOWFISH study will help determine the therapeutic dose of risprom in children under 2 months of age
.

 RAINBOWFISH: Preliminary Efficacy and Safety Data in Risdiplam-Treated Infants with Presymptomatic SMA (Full Text Access) Safety and Efficacy of SRP-9001 in Duchenne Muscular Dystrophy SRP-9001 is an investigational gene transfer therapy for targeted expression Shortened functional trace dystrophin in skeletal and cardiac muscle, this study evaluated the safety and efficacy of SRP-9001 in patients with Duchenne muscular dystrophy
.

The Phase II study is divided into 3 parts, the first part is a 48-week randomized, double-blind, placebo-controlled period
.

Part 2 involved patients who received placebo in Part 1 to receive 48 weeks of SRP-9001
.

Part 3 is an open-label extension period, continuing treatment for 212 weeks
.

The study included DMD patients aged 4-7 years with confirmed DMD mutations in exons 18-58 who received fixed doses of steroids and were randomized to SRP-0001 (n=20) and placebo (n=21) , the expected dose is 2.
0*1014vg/kg (supercoiled qPCR, linear plasmid standard equivalent 1.
33×1014vg/kg)
.

Subsequent stratification by age (4-5 years and 6-7 years), the primary endpoints were micro-dystrophin expression (Western blot; week 12) and Polaris dynamic assessment (week 48) compared to baseline changes
.

Safety endpoints included serious adverse events and treatment-emergent adverse events
.

Complete data from Parts 1 and 2, presented at this meeting, demonstrate that SRP-9001 has biological effects that may be clinically relevant in patients with DMD
.

The results reinforce a potentially favorable benefit-risk profile
.

 A Phase 2 Clinical Trial Evaluating the Safety and Efficacy of SRP-9001 for Treating Patients with Duchenne Muscular Dystrophy demand
.

Roche has been committed to the research in the field of rare diseases, to find more effective and safer treatment drugs and solutions for patients
.

The latest research data also further validates the efficacy and safety of these rare disease drugs, and it is expected that their application will bring more clinical benefits to rare disease patients and improve their quality of life
.

 References: 1.
Long-term Efficacy of Satralizumab in Aquaporin-4-IgG-seropositive Neuromyelitis Optica Spectrum Disorder (NMOSD): Results from the Open-label Extension Periods of SAkuraSky and SAkuraStar (S25.
009) 2.
Efficacy and Safety of Ocrelizumab in Patients With RRMS With SuboptimalResponse to Prior Disease-Modifying Therapies: 3-Year Data From CASTING and LIBERTO (LIBERTO 1-Year Interim Results)(P5.
003)3.
SUNFISH: 3-year Efficacy and Safety of Risdiplam in Types 2 and 3 SMA(S39.
003)4.
RAINBOWFISH: Preliminary Efficacy and Safety Data in Risdiplam-TreatedInfants with Presymptomatic SMA(P17.
003)5.
A Phase 2 Clinical Trial Evaluating the Safety and Efficacy of SRP-9001for Treating Patients with Duchenne Muscular Dystrophy( S23.
002) The materials presented on this website are professional materials intended to facilitate the communication and exchange of medical information
.

The content may contain drugs or clinical indications that are not approved in China, and are only for reference by medical and health professionals.
For prescriptions, please refer to the drug insert approved by the State Drug Administration
.