Vamorolon (1) – Agamree®

• Clinical trials
  • The VISION-DMD trial is a randomised, double-blind, placebo- and active-controlled Phase IIb trial comparing two doses of vamorolon (2.0 mg/kg/day and 6.0 mg/kg/day) with prednisone (0.75 mg/kg/day) or placebo.
  • The FOR-DMD study is a randomised, controlled trial investigating three corticosteroid dosing regimens in corticosteroid-naïve patients aged between 4 and 7 years with DMD.

Patients aged 4 years and over with Duchenne muscular dystrophy

• For patients aged 4 years and over with Duchenne muscular dystrophy, there is a hint of a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• mortality
  • In the VISION-DMD study, no deaths occurred during treatment phase 1 (week 24).
• Morbidity – Time-to-Stand Test (TTSTAND)
  • The TTSTAND endpoint measures the time (in seconds) taken by a patient to move from a supine position on the floor to an upright standing position (‘time to stand’). This endpoint is considered patient-relevant for the indicated therapeutic indication.
  • For the ‘time to stand’ endpoint (TTSTAND), no statistically significant differences were observed between the treatment groups at week 24.
• Morbidity – 10 m walking/running distance (TTRW)
  • For the endpoint ‘10-metre walking/running distance’ (TTRW), the time taken by the patient to walk or run 10 metres is measured. This endpoint is considered patient-relevant in this therapeutic indication.
  • No statistically significant differences were observed between the treatment groups.
• Morbidity – Climbing 4 steps (TTCLIMB)
  • The endpoint ‘climbing 4 steps’ (TTCLIMB) measures the time taken by the patient to climb four steps.
  • This endpoint is considered patient-relevant in this therapeutic indication.
  • No descriptive data could be identified for the two assessment time points (baseline and week 24). A conclusive assessment of the results is therefore not possible.
  • There are no statistically significant differences between the treatment groups.
• Morbidity – 6-minute walk test (6MWT)
  • The 6-minute walk test (6MWT) is used to assess physical functioning and measures the distance a patient can walk within 6 minutes. This endpoint is considered patient-relevant in the therapeutic indication.
  • For the ‘6MWT’ endpoint, no statistically significant differences were observed between the treatment groups at week 24.
• quality of life
  • No data on quality of life were collected.
• Side effects
  • During treatment phase 1 (week 24), one severe adverse event (AE) (preferred term ‘aggression’) and one case of therapy discontinuation due to an AE, each in one patient in the prednisone treatment arm; no significant differences were observed between the treatment groups. No serious AEs occurred during this period in the VISION-DMD study.
• Overall assessment / Conclusion
  • No deaths occurred in the study; therefore, no conclusions regarding the extent of the additional benefit can be drawn for the mortality category.
  • In the morbidity endpoint category, there were no significant differences between the treatment groups for the endpoints Time-to-Stand Test (TTSTAND), 10-metre walking/running distance (TTRW), climbing 4 steps (TTCLIMB) and the 6-minute walk test (6MWT). Consequently, no conclusions regarding the extent of the additional benefit can be drawn for the morbidity category either.
  • In the ‘Side Effects’ category, there were no significant differences between the treatment groups for either severe AEs or therapy discontinuations due to AEs. No severe AEs occurred. With regard to the anthropometric parameters assessed as safety endpoints, a statistically significant difference in favour of vamorolon was observed for the endpoint of height (z-scores), whilst a statistically significant difference to the detriment of vamorolon was observed for the endpoint of body weight (z-score). Taking into account imbalances in the baseline values and the availability of comparative data for the endpoints of height and body weight over a relatively short period of 24 weeks, it cannot be concluded that these are clinically relevant effects. Consequently, no conclusions can be drawn regarding the extent of the additional benefit in the category of side effects either.
  • Overall, therefore, there is a non-quantifiable additional benefit for patients aged 4 years and over with Duchenne muscular dystrophy, as the scientific evidence does not permit quantification.
• Overall assessment / Conclusion
  • No deaths occurred in the study; consequently, no conclusions regarding the extent of the additional benefit can be drawn for the ‘Mortality’ category.
  • In the morbidity endpoint category, there were no significant differences between the treatment groups for the endpoints Time-to-Stand Test (TTSTAND), 10-metre walking/running distance (TTRW), climbing 4 steps (TTCLIMB) and the 6-minute walk test (6MWT). Consequently, no conclusions regarding the extent of the additional benefit can be drawn for the morbidity category either.
  • In the ‘Side Effects’ category, there were no significant differences between the treatment groups for either severe AEs or therapy discontinuations due to AEs. No serious AEs occurred. With regard to the anthropometric parameters assessed as safety endpoints, a statistically significant difference in favour of vamorolon was observed for the endpoint of height (z-scores), whilst a statistically significant difference to the detriment of vamorolon was observed for the endpoint of body weight (z-score). Taking into account imbalances in the baseline values and the availability of comparative data for the endpoints of height and body weight over a relatively short period of 24 weeks, it cannot be concluded that these are clinically relevant effects. Consequently, no conclusions can be drawn regarding the extent of the additional benefit in the category of side effects either.
  • Overall, therefore, there is a non-quantifiable additional benefit for patients aged 4 years and over with Duchenne muscular dystrophy, as the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.