Select Language
veoza-hcp-global-en-efficacy-and-safety
veoza-hcp-global-en-efficacy-and-safety

VEOZAH demonstrated efficacy in moderate to severe VMS due to menopause1

The efficacy of VEOZAH was evaluated in the first 12-week, randomized, placebo-controlled, double-blind portion of the SKYLIGHT 1 and 2 Phase 3 studies. After the first 12 weeks, women on placebo were then re-randomized to VEOZAH for a 40-week extension to evaluate safety for up to 52 weeks total exposure. Coprimary endpoints were mean change from baseline in moderate to severe VMS frequency and severity at Weeks 4 and 12.1

VEOZAH provided clinically meaningful (≥2 hot flashes per 24 hours) reductions in the frequency of moderate to severe VMS and provided statistically significant reductions in the severity of moderate to severe VMS vs. placebo1

FREQUENCY (Coprimary endpoint)

Frequency
Frequency

SD: standard deviation; SE: standard error. 

* Statistically significantly superior compared to placebo at the 0.05 level with multiplicity adjustment.1

FREQUENCY: Measured as a daily mean and analyzed as weekly average (calculated as the average frequency over nonmissing days from 7 days).3,4

LS Mean: least squares mean estimated from a mixed model for repeated measures analysis of covariance.1

Skylight 2
skylight-2-frequency

SD: standard deviation; SE: standard error. 

* Statistically significantly superior compared to placebo at the 0.05 level with multiplicity adjustment.1 

FREQUENCY: Measured as a daily mean and analyzed as weekly average (calculated as the average frequency over nonmissing days from 7 days).3,4

LS Mean: least squares mean estimated from a mixed model for repeated measures analysis of covariance.1

In SKYLIGHT 2

Statistically significant difference between VEOZAH vs. placebo was observed at Week 1 for VMS frequency (secondary endpoint).2,3,5

 

  • Mean (SD) change from baseline in VMS frequency with VEOZAH: 3.91 (4.30) vs. 2.34 (3.34) with placebo
  • Baseline (SD) VMS frequency in VEOZAH group 11.8 (8.26) vs. 11.6 (5.02) with placebo
  • LS mean difference vs. placebo (SE): -1.71 (0.40); 95% CI: -2.51, -0.91; p<0.001, without multiplicity analysis

 

The secondary endpoint of change in frequency of VMS from baseline to Week 12 did not reach statistical significance within the SKYLIGHT 1 study.

SEVERITY (Coprimary endpoint)

Severity
Severity

SD: standard deviation; SE: standard error. 

† Statistically significantly superior compared to placebo at the 0.05 level with multiplicity adjustment.1

SEVERITY: Measured as a daily mean and analyzed as weekly average.3,4

LS Mean: least squares mean estimated from a mixed model for repeated measures analysis of covariance.1

Skylight 2
Skylight 2

SD: standard deviation; SE: standard error. 

† Statistically significantly superior compared to placebo at the 0.05 level with multiplicity adjustment.1

SEVERITY: Measured as a daily mean and analyzed as weekly average.3,4

LS Mean: least squares mean estimated from a mixed model for repeated measures analysis of covariance.1

VEOZAH Week 52 data2-4

FREQUENCY

Frequency
Frequency

Mean change in the frequency of VMS from baseline to each visit in the extension period was an exploratory endpoint. Assessments after the 12-week placebo-controlled period were descriptive only.2,4

The duration of this study is longer than that of the efficacy data in the VEOZAH Product Monograph.

Skylight 2
Skylight 2

Mean change in the frequency of VMS from baseline to each visit in the extension period was an exploratory endpoint. Assessments after the 12-week placebo-controlled period were descriptive only.2,4

The duration of this study is longer than that of the efficacy data in the VEOZAH Product Monograph.

SEVERITY

Frequency
Frequency

Mean change in the severity of VMS from baseline to each visit in the extension period was an exploratory endpoint. Assessments after the 12-week placebo-controlled period were descriptive only.2,4

The duration of this study is longer than that of the efficacy data in the VEOZAH Product Monograph

Skylight 2
Skylight 2

Mean change in the severity of VMS from baseline to each visit in the extension period was an exploratory endpoint. Assessments after the 12-week placebo-controlled period were descriptive only.2,4

The duration of this study is longer than that of the efficacy data in the VEOZAH Product Monograph.

VEOZAH demonstrated powerful reductions in VMS-related, self-reported sleep disturbances (as measured by the PROMIS SD SF 8B; key secondary endpoint)3

Promois SD SF Chart
veoza-adverse-image.png

The key secondary endpoint of sleep disturbance did not reach statistical significance within the SKYLIGHT 1 study.

 

PROMIS SD SF 8b assesses self-reported sleep disturbance during the prior 7 days and includes perceptions of:3

 

  • Restless sleep 
  • Satisfaction with sleep 
  • Refreshing sleep 
  • Difficulties sleeping 
  • Difficulties getting to sleep 
  • Difficulties staying asleep 
  • Amount of sleep 
  • Sleep quantity 

 

Responses to the 8 items range from 1 to 5, and the range of possible summed raw scores is 8 to 40. Higher scores on PROMIS SD SF 8b indicate more disturbed sleep. 

 

 

LS: least squares; PROMIS SD SF 8b: Patient-Reported Outcomes Measurement Information System Sleep Disturbance – Short Form 8b; SD: standard deviation; SE: standard error.

§ Two-sided unadjusted p value.3

VEOZAH has a generally well-tolerated safety profile1

VEOZAH: Demonstrated safety and tolerability profile up to 1 year

The safety profile of VEOZAH was evaluated in Phase 3 clinical studies

SKYLIGHT 1 & 2

TWO identically designed Phase 3 efficacy and safety studies that were randomized, placebo-controlled, double-blind for 12 weeks, followed by rerandomization of women previously receiving placebo to VEOZAH (women on VEOZAH remained on VEOZAH) for an additional 40 weeks of uncontrolled treatment.

SKYLIGHT 4

ONE Phase 3, 52-week, randomized, placebo-controlled, double-blind study evaluating long-term safety.

12-week safety profile

12-week safety profile Graph

12-week safety profile Graph

Abdominal pain includes abdominal lower pain, abdominal upper pain, and abdominal tenderness.1

†† Liver test elevation includes alanine aminotransferase abnormal/increased, aspartate aminotransferase abnormal/increased, blood alkaline phosphatase abnormal/increased, blood bilirubin increased, gamma-glutamyltransferase increased, hepatic enzyme abnormal/increased, transaminases increased, and liver function test abnormal/increased.1

The most common adverse drug reaction during the 12-week placebo-controlled period in SKYLIGHT 1 and 2 (≥3% in patients receiving VEOZAH 45 mg and greater than placebo) was liver test elevation (3.2%).1

52-week safety profile

52-week safety profile Graph

12-week safety profile Graph

Abdominal pain includes abdominal lower pain, abdominal upper pain, and abdominal tenderness.1

‡‡ Liver test elevation includes alanine aminotransferase abnormal/increased, aspartate aminotransferase abnormal/increased, blood alkaline phosphatase increased, blood bilirubin increased, gamma-glutamyltransferase increased, hepatic function abnormal, hepatic enzyme increased, transaminases increased, and liver function test abnormal/increased.1

During the 52-week placebo-controlled period in SKYLIGHT 4, the most frequent adverse drug reactions (≥3% in patients receiving VEOZAH 45 mg and greater than placebo) were headache (9.7%), liver test elevation (5.3%), abdominal pain (4.4%), diarrhea (3.9%), insomnia (3.9%), and nausea (3.1%).1

A numerical imbalance was observed in the incidence of other malignancies between VEOZAH and placebo groups in the long-term safety SKYLIGHT 4. A causal relationship between VEOZAH and increased risk of malignancies has not been established.1

Consider VEOZAH—a NEW option to treat moderate to severe VMS1

Learn about VEOZAH dosing and administration

Sign up for exclusive VEOZAH updates and product information

Important Safety Information

Indication body title

Clinical use:

  • Pediatrics (<18 years of age): not indicated.
  • Geriatrics (≥65 years of age): no data available; therefore, an indication has not been recommended.

Contraindications:

  • Known cirrhosis
  • Severe renal impairment or end-stage renal disease
  • Patients using concomitant moderate or strong CYP1A2 inhibitors
  • Known or suspected pregnancy

Relevant warnings and precautions:

  • Benefit-risk consideration to treat women with known or previous breast cancer or other estrogen-dependent malignancies
  • Not recommended in Child-Pugh Class B (moderate) chronic hepatic impairment; not studied in Child-Pugh Class C (severe) chronic hepatic impairment and is not recommended in this population
  • Risk of hepatic transaminase elevation and hepatotoxicity
  • Perform baseline bloodwork to evaluate hepatic function and assess for injury (including serum ALT, serum AST, serum ALP, and serum bilirubin [total and direct]) prior to initiating VEOZAH. Perform hepatic laboratory tests monthly for the first 3 months, at 6 months, and 9 months after initiation of therapy
  • Incidence of other malignancies; a causal relationship between VEOZAH and increased risk of malignancies has not been established
  • Risk of endometrial hyperplasia and endometrial carcinoma. In the VEOZAH 45 mg dose group across the three phase 3 studies, endometrial biopsy assessments identified one case of endometrial hyperplasia and one case of endometrial malignancy (0.6% with a one-sided upper limit of 95% confidence of 1.8%). The rate of these events in the VEOZAH 45 mg dose group was ≤1% with the upper bound of the one-sided 95% confidence limit being ≤4%. There was no case of endometrial hyperplasia or carcinoma in the placebo group
  • Not recommended in breast-feeding women

For more information:

Consult the Product Monograph at www.veozahmonograph.ca for important information relating to adverse reactions, drug interactions and dosing information. The Product Monograph is also available by calling 1-888-338-1824.

Important Safety Information

Indication body title

Clinical use:

  • Pediatrics (<18 years of age): not indicated.
  • Geriatrics (≥65 years of age): no data available; therefore, an indication has not been recommended.

Contraindications:

  • Known cirrhosis
  • Severe renal impairment or end-stage renal disease
  • Patients using concomitant moderate or strong CYP1A2 inhibitors
  • Known or suspected pregnancy

Relevant warnings and precautions:

  • Benefit-risk consideration to treat women with known or previous breast cancer or other estrogen-dependent malignancies
  • Not recommended in Child-Pugh Class B (moderate) chronic hepatic impairment; not studied in Child-Pugh Class C (severe) chronic hepatic impairment and is not recommended in this population
  • Risk of hepatic transaminase elevation and hepatotoxicity
  • Perform baseline bloodwork to evaluate hepatic function and assess for injury (including serum ALT, serum AST, serum ALP, and serum bilirubin [total and direct]) prior to initiating VEOZAH. Perform hepatic laboratory tests monthly for the first 3 months, at 6 months, and 9 months after initiation of therapy
  • Incidence of other malignancies; a causal relationship between VEOZAH and increased risk of malignancies has not been established
  • Risk of endometrial hyperplasia and endometrial carcinoma. In the VEOZAH 45 mg dose group across the three phase 3 studies, endometrial biopsy assessments identified one case of endometrial hyperplasia and one case of endometrial malignancy (0.6% with a one-sided upper limit of 95% confidence of 1.8%). The rate of these events in the VEOZAH 45 mg dose group was ≤1% with the upper bound of the one-sided 95% confidence limit being ≤4%. There was no case of endometrial hyperplasia or carcinoma in the placebo group
  • Not recommended in breast-feeding women

For more information:

Consult the Product Monograph at www.veozahmonograph.ca for important information relating to adverse reactions, drug interactions and dosing information. The Product Monograph is also available by calling 1-888-338-1824.

*Comparative clinical significance unknown.

†SKYLIGHT 2 was a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, study in which post-menopausal women were randomized to VEOZAH 45 mg (n=167) or placebo (n=167) once daily for 12 weeks. After the 12-week, double-blind treatment period, all patients received VEOZAH for a 40-week extension treatment period with women on placebo re-randomized to VEOZAH to evaluate safety for up to 52 weeks total exposure. The study included post-menopausal women who had a minimum average of 7 moderate to severe VMS per day. The coprimary efficacy endpoints were change from baseline in moderate to severe VMS frequency and severity to weeks 4 and 12. Baseline mean frequency of moderate to severe VMS per 24 hours: 11.8 for VEOZAH, 11.6 for placebo.1

‡Clinical significance is unknown.

REFERENCES: 1. VEOZAH Product Monograph. Markham, ON: Astellas Pharma Canada, Inc. 2. Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401(10382):1091-102. 3. Johnson KA, Martin N, Nappi RE, et al. Efficacy and safety of fezolinetant in moderate to severe vasomotor symptoms associated with menopause: a phase 3 RCT. J Clin Endocrinol Metab. (Epub) 02-03-2023. 4. Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study (supplementary appendix). Lancet. 2023;401(10382):1-14. 5. Data on file. Clinical efficacy summary.