Vibegron (1) – Obgemsa®

• Clinical trials
  • The randomised, controlled, double-blind, multicentre study 3003 investigated the administration of vibegron compared with tolterodine or placebo in adults diagnosed with overactive bladder.
  • The randomised, controlled, double-blind, multicentre study 3004 investigated the administration of vibegron compared with tolterodine over 40 weeks.

Adults with overactive bladder

• An additional benefit is not proven.
• Overall, it is concluded that, for adults with an overactive bladder, the additional benefit of vibegron over the appropriate comparator therapy, tolterodine, is not proven.
• mortality
  • No deaths occurred in studies 3003 and 3004.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint, assessed using the EQ-5D visual analogue scale (VAS), there was no statistically significant difference between the treatment groups.
• Morbidity – Symptoms (Symptom Bother Score, PGI-Change, PGI-Severity and PGI-Control)
  • Responder analyses, which reflect an improvement, are used for the benefit assessment.
  • Overall, no statistically significant difference was observed between the treatment groups for any of the endpoints.
• Morbidity – Incontinence
  • For the endpoints of incontinence and urge incontinence, the differences in mean values indicate a statistically significant advantage for vibegron compared with tolterodine.
  • However, it cannot be inferred from the corresponding effect estimates and associated 95% confidence intervals that the mean difference of half an incontinence episode between the two treatment arms represents clinically relevant effects.
  • This assessment is also made against the background that the advantages are not reflected in other patient-relevant endpoints such as urinary frequency, urgent urge to urinate or nocturia.
• Morbidity – urge incontinence
  • For the endpoints of incontinence and urge incontinence, the mean differences show a statistically significant advantage for vibegron compared with tolterodine in each case.
  • However, it cannot be inferred from the corresponding effect estimates and associated 95% confidence intervals that the mean difference of half an incontinence episode between the two treatment arms represents clinically relevant effects.
  • This assessment is also made against the background that the advantages are not reflected in other patient-relevant endpoints such as urinary frequency, urgent urge to urinate or nocturia.
• Morbidity – Urination frequency
  • For the endpoints of micturition frequency, urge incontinence and nocturia, no statistically significant difference was observed between the treatment groups.
• Morbidity – Urge to urinate
  • For the endpoints of frequency of urination, urge to urinate and nocturia, there is no statistically significant difference between the treatment groups in each case.
• Health-related quality of life
  • Health-related quality of life was assessed using the OAB-q LF.
  • For the benefit assessment, responder analyses were used, which reflect a clinically relevant improvement.
  • No statistically significant difference was observed between the treatment groups.
  • However, there is an effect modification by the characteristic ‘age’: for individuals aged ≥ 65 years, there is a statistically significant improvement in quality of life in the vibegron arm compared with the tolterodine arm.
  • For individuals < 65 years of age, there is still no statistically significant difference.
  • However, this effect modification is not reflected in any other patient-relevant endpoints.
  • Furthermore, the medical rationale for this age limit is unclear.
  • Overall, the findings regarding the observed effect modification by the ‘age’ characteristic are not considered sufficient to allow separate conclusions to be drawn in the overall assessment regarding the additional benefit for individuals < 65 years and ≥ 65 years.
• Side effects – severe adverse events (SAEs), severe AEs and discontinuation due to AEs
  • No statistically significant difference was observed between the treatment groups for the overall rates of serious adverse events (SAEs), severe AEs and discontinuation due to AEs.
• Overall assessment
  • The results of studies 3003 and 3004 are available.
  • For the assessment of additional benefit, only the patient population that was treated with vibegron or tolterodine during both studies – and thus continuously over a period of 52 weeks – is considered.
  • No deaths occurred in the studies.
  • For the morbidity endpoint category, there was no statistically significant difference between the treatment groups for the endpoints of health status (EQ-5D VAS), symptoms (assessed using the Symptom Bother Score, PGI-Change, PGI-Severity and PGI-Control), frequency of micturition, imperative urge to urinate and nocturia.
  • For the endpoints of incontinence and urge incontinence, the differences in mean values indicate a statistically significant advantage for vibegron compared with tolterodine.
  • However, the reduction of half an incontinence episode per day is not considered a clinically relevant advantage.
  • This assessment is also made against the background that the advantages are not reflected in other patient-relevant endpoints such as urinary frequency, urgent urinary urge or nocturia.
  • For the endpoint category of health-related quality of life, assessed using the OAB-q LF, there is no statistically significant difference between the treatment groups.
  • There is an effect modification by the characteristic ‘age’.
  • For individuals aged ≥ 65 years, there is a statistically significant improvement in quality of life in favour of vibegron compared with tolterodine.
  • However, the results of the observed effect modification by the characteristic ‘age’ are not considered sufficient to allow separate conclusions to be drawn in the overall assessment regarding the additional benefit for individuals < 65 years and ≥ 65 years.
  • For the endpoint category of side effects, there is no statistically significant difference between the treatment groups in the overall rates of serious adverse events (SAEs), severe adverse events and discontinuation due to adverse events.
  • In detail, a statistically significant advantage of vibegron over tolterodine was observed for the AEs ‘dry mouth’ and ‘dizziness’.
  • Taking the results in the side effect category as a whole, no additional benefit of vibegron compared with tolterodine is identified.
  • Overall, it is concluded that, for adults with an overactive bladder, the additional benefit of vibegron over the appropriate comparator therapy is not proven.

Courtesy translation only, please refer to the German original.