Ponesimod (2) – Ponvory®
Relaps multiple sclerosis (MS)
Characteristics
| Start date | 01.12.2021 |
|---|---|
| Resolution | 19.05.2022 |
| INN | Ponesimod |
| Brand name | Ponvory® |
| Pharm. company |
Dossier: Janssen-Cilag GmbH
New distributor: LABORATOIRES JUVISE PHARMACEUTICALS |
| G-BA Procedure ID | D-766 |
| ATC code | L04AE04 IMMUNOSUPPRESSANTS (L04A) |
| ICD-10 codes (AIS) | G35.10, G35.11, G35.30, G35.31, G35.9 |
| Alpha-ID codes (AIS) | I98549Multiple sclerosis with predominantly relapsing-remitting course, I98551Multiple sclerosis with secondary-chronic course, I99339Multiple sclerosis |
| DDD | 20 mg O |
| Therapeutic area | Nervous system diseases Multiple sclerosis (MS) / Neuromyelitis optica spectrum disorders (NMOSD) |
| Reason for procedure | Initial assessment |
| Specialty | ACT change |
| Therapeutic indication of the resolution |
|---|
|
Ponvory is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features. |
| Subpopulation | Indication | Comparator |
|---|---|---|
| a1) | Adults with relapsing-remitting multiple sclerosis (RMS) who have not yet received disease-modifying therapy or adults pre-treated with disease-modifying therapy whose disease is not highly active; EDSS score ≤ 3.5). | Interferon beta-1a or interferon beta-1b or glatiramer acetate or dimethyl fumarate or teriflunomide or ocrelizumab taking into account the marketing authorisation. |
| a2) | Adults with relapsing-remitting multiple sclerosis (RMS) who have not yet received disease-modifying therapy or adults pre-treated with disease-modifying therapy whose disease is not highly active; EDSS score > 3.5). | Interferon beta-1a or interferon beta-1b or glatiramer acetate or dimethyl fumarate or teriflunomide or ocrelizumab taking into account the marketing authorisation. |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (OPTIMUM) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. ACT |
|
Meta analysis
(best subpopulation) |
no |
| Reason for dividing into subpopulations (G-BA) | Disease stage |
| ACT change | 02.12.2021 – Neue Leitlinien |
- Clinical trials
- To assess the additional benefit of ponesimod, the pharmaceutical manufacturer has submitted the randomised, double-blind OPTIMUM trial, in which ponesimod was compared with teriflunomide.
a1) Adults with relapsing-remitting multiple sclerosis (RRMS) who have not yet received disease-modifying therapy, or adults previously treated with disease-modifying therapy whose disease is not highly active; EDSS score ≤ 3.5
- Overall, therefore, there is an indication of a minor additional benefit of ponesimod compared with teriflunomide in adults with an EDSS score ≤ 3.5.
- mortality
- The findings on overall mortality are based on data on fatal adverse events. No statistically significant difference was observed between the treatment groups.
- Morbidity – Confirmed relapses (EDSS-based)
- For the endpoint of confirmed relapses, operationalised as the annual relapse rate, there is a statistically significant advantage in favour of ponesimod compared with teriflunomide.
- Whilst a statistically significant advantage in favour of ponesimod continues to be observed for adults with an EDSS score ≤ 3.5 (mild disability), no statistically significant difference between the treatment groups can be demonstrated for adults with an EDSS score > 3.5 (more severe disability), no statistically significant difference between the treatment groups can be demonstrated.
- Morbidity – Confirmed disability progression (EDSS-based)
- No statistically significant difference between the treatment groups was observed for the endpoint of confirmed disability progression.
- Morbidity – Severity of disability (Multiple Sclerosis Functional Composite [MSFC])
- For the endpoint of severity of disability, assessed using the MSFC z-score, there is a statistically significant advantage of ponesimod over teriflunomide. However, the 95% confidence interval for Hedges’ g does not lie entirely above the irrelevance threshold of 0.20. It cannot therefore be concluded that the effect is clinically relevant.
- Morbidity – Fatigue (Patient Global Impression of Severity [PGI-S])
- For the endpoint of fatigue, assessed using the PGI-S, there is no statistically significant difference between the treatment groups.
- Health-related quality of life – Short Form-36 Health Survey Version 2 (SF-36v2)
- Whilst a statistically significant advantage in favour of ponesimod over teriflunomide continues to be observed for adults with an EDSS score ≤ 3.5 (mild disability), no statistically significant difference between the treatment groups can be demonstrated for adults with an EDSS score > 3.5 (more severe disability), no statistically significant difference between the treatment groups can be demonstrated.
- For the mental health summary score (MCS) of the SF-36v2, there is no statistically significant difference between the treatment groups in terms of either improvement or deterioration compared with the start of the study.
- Side effects – SUEs
- No statistically significant difference was observed between the treatment groups for the SUEs endpoint.
- Side effects – discontinuation due to AEs
- For the endpoint ‘withdrawal due to AEs’, no statistically significant difference was observed between the treatment groups.
- Side effects – bradycardia (PT, AE)
- For the endpoint ‘bradycardia’, there was a statistically significant difference between the treatment groups, with a disadvantage for ponesimod compared with teriflunomide.
- Side effects – Infections and parasitic diseases (SOC, SAE)
- For the endpoint ‘infections and parasitic diseases’, there was no statistically significant difference between the treatment groups.
- Side effects – alopecia (PT, AE)
- For the endpoint alopecia, there is a statistically significant advantage for ponesimod over teriflunomide.
- Overall assessment
- In adults with an EDSS score ≤ 3.5 (mild disability), ponesimod showed an advantage over teriflunomide in terms of morbidity (confirmed relapses) and health-related quality of life (SF-36v2, physical summary score). However, these observed advantages are not reflected in other patient-relevant endpoints such as disability progression or fatigue.
- Based on the adverse reaction profile, it cannot be concluded that ponesimod causes either greater or minor harm overall.
- The effects of ponesimod are therefore assessed, in adults with an EDSS score ≤ 3.5, as a moderate—rather than merely minor—improvement in treatment-related benefit compared with the appropriate comparator therapy, which has not been achieved to date, and the extent of the additional benefit is classified as minor.
- Overall, therefore, for ponesimod in the treatment of adults with relapsing-remitting multiple sclerosis who have not yet received disease-modifying therapy, or adults previously treated with disease-modifying therapy whose disease is not highly active, and who have an EDSS score of ≤ 3.5, a minor additional benefit compared with teriflunomide.
a2) Adults with relapsing-remitting multiple sclerosis (RRMS) who have not yet received disease-modifying therapy, or adults who have previously been treated with disease-modifying therapy and whose disease is not highly active; EDSS score > 3.5
- Overall, therefore, no additional benefit of ponesimod over teriflunomide can be established in adults with an EDSS score > 3.5.
- The additional benefit is not proven.
- mortality
- The findings on overall mortality are based on data on fatal adverse events. No statistically significant difference was observed between the treatment groups.
- Morbidity – Confirmed relapses (EDSS-based)
- Whilst a statistically significant advantage in favour of ponesimod continues to be observed for adults with an EDSS score ≤ 3.5 (mild disability), no statistically significant difference between the treatment groups can be demonstrated for adults with an EDSS score > 3.5 (more severe disability), no statistically significant difference between the treatment groups can be demonstrated.
- Morbidity – Confirmed disability progression (EDSS-based)
- For the endpoint of confirmed disability progression, no statistically significant difference was observed between the treatment groups.
- Morbidity – Severity of disability (Multiple Sclerosis Functional Composite [MSFC])
- For the endpoint of severity of disability, assessed using the MSFC z-score, there is a statistically significant advantage of ponesimod over teriflunomide. However, the 95% confidence interval for Hedges’ g does not lie entirely above the irrelevance threshold of 0.20. It cannot therefore be concluded that the effect is clinically relevant.
- Morbidity – Fatigue (Patient Global Impression of Severity [PGI-S])
- For the endpoint of fatigue, assessed using the PGI-S, there is no statistically significant difference between the treatment groups.
- Health-related quality of life – Short Form-36 Health Survey Version 2 (SF-36v2)
- Whilst a statistically significant advantage in favour of ponesimod over teriflunomide continues to be observed for adults with an EDSS score ≤ 3.5 (mild disability), no statistically significant difference between the treatment groups can be demonstrated for adults with an EDSS score > 3.5 (more severe disability), no statistically significant difference between the treatment groups can be demonstrated.
- For the mental health summary score (MCS) of the SF-36v2, there is no statistically significant difference between the treatment groups in terms of either improvement or deterioration compared with baseline.
- Side effects – SUEs
- No statistically significant difference was observed between the treatment groups for the SUEs endpoint.
- Side effects – discontinuation due to AEs
- For the endpoint ‘withdrawal due to AEs’, no statistically significant difference was observed between the treatment groups.
- Side effects – bradycardia (PT, AE)
- For the endpoint ‘bradycardia’, there was a statistically significant difference between the treatment groups, with a disadvantage for ponesimod compared with teriflunomide.
- Side effects – Infections and parasitic diseases (SOC, SAE)
- For the endpoint ‘infections and parasitic diseases’, there was no statistically significant difference between the treatment groups.
- Side effects – alopecia (PT, AE)
- For the endpoint alopecia, there is a statistically significant advantage for ponesimod over teriflunomide.
- Overall assessment
- In adults with an EDSS score > 3.5 (more severe disability), no statistically significant differences were observed between the treatment groups for the endpoints of mortality, morbidity and health-related quality of life.
- With regard to side effects, no overall increase or minor decrease in harm attributable to ponesimod can be inferred for this patient group either.
- Overall, the additional benefit of ponesimod over teriflunomide in adults with an EDSS score > 3.5 is not proven.
Courtesy translation only, please refer to the German original.
Associated procedures
| Ponesimod (2) | Ponvory® | Janssen-Cilag GmbH | Relaps multiple sclerosis (MS) | 186,000–200,000 | 50% Indication of minor additional benefit | |
| Ponesimod (1) | Ponvory® | Janssen-Cilag GmbH | Relapsing multiple sclerosis (MS) | 21,000–23,000 | 100% additional benefit not proven |
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