Trial Outcomes & Findings for Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (NCT NCT03470545)

Last Updated: 2021-10-04

Results Overview

A positive clinical response (value="YES") is defined as having achieved either an improvement of at least 1.5 mL/kg/min in peak oxygen consumption (pVO2) as determined by cardiopulmonary exercise testing (CPET) and a reduction of one or more class in New York Heart Association (NYHA) functional classification (e.g.I, II, III, or IV) -OR- an improvement of 3.0 mL/kg/min or more in pVO2 with no worsening in NYHA Functional Class.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

251 participants

Primary outcome timeframe

30 weeks

Results posted on

2021-10-04

Participant Flow

Subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled into the study and were randomized 1:1 to receive mavacamten (2.5, 5, 10, or 15 mg capsule) or placebo once daily for 30 weeks, followed by an 8 week post-treatment period. In total, 429 participants were assessed for eligibility and 251 were enrolled from 68 sites in the United States and EMEA.

Participant milestones

Participant milestones
Measure	Mavacamten (MYK-461) Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 8 and Week 14, mavacamten dose may have been up-titrated for individual subjects based on prespecified criteria. Down-titration was possible at Week 6, Week 8, Week 14, Week 18, Week 22 and Week 26 for individual subjects based on prespecified criteria.	Placebo Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.
Overall Study STARTED	123	128
Overall Study COMPLETED	119	125
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Mavacamten (MYK-461) Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 8 and Week 14, mavacamten dose may have been up-titrated for individual subjects based on prespecified criteria. Down-titration was possible at Week 6, Week 8, Week 14, Week 18, Week 22 and Week 26 for individual subjects based on prespecified criteria.	Placebo Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.
Overall Study Death	0	1
Overall Study Did not complete Week 30 assessments due to scheduling conflict	1	0
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	1	1
Overall Study Week 30 not completed due to circumstances surrounding the COVID-19 pandemic	0	1

Baseline Characteristics

Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mavacamten (MYK-461) n=123 Participants mavacamten: mavacamten capsules	Placebo n=128 Participants Placebo: placebo oral capsule	Total n=251 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	78 Participants n=99 Participants	88 Participants n=107 Participants	166 Participants n=206 Participants
Age, Categorical >=65 years	45 Participants n=99 Participants	40 Participants n=107 Participants	85 Participants n=206 Participants
Age, Continuous	60 years n=99 Participants	60 years n=107 Participants	60 years n=206 Participants
Sex: Female, Male Female	57 Participants n=99 Participants	45 Participants n=107 Participants	102 Participants n=206 Participants
Sex: Female, Male Male	66 Participants n=99 Participants	83 Participants n=107 Participants	149 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=99 Participants	4 Participants n=107 Participants	12 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	114 Participants n=99 Participants	119 Participants n=107 Participants	233 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	5 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	4 Participants n=99 Participants	2 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	5 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) White	115 Participants n=99 Participants	114 Participants n=107 Participants	229 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=99 Participants	6 Participants n=107 Participants	9 Participants n=206 Participants

PRIMARY outcome

Timeframe: 30 weeks

Outcome measures

Outcome measures
Measure	Mavacamten (MYK-461) n=123 Participants Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.	Placebo n=128 Participants Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.
Percentage of Participants Achieving A Clinical Response	45 Participants	22 Participants

SECONDARY outcome

Timeframe: 30 weeks

The post-exercise LVOT gradient was measured from echocardiograms obtained at baseline and week 30 following a study-specified exercise protocol and read by the Cardiovascular Imaging Core Laboratory (CICL, Boston MA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.

Outcome measures

Outcome measures
Measure	Mavacamten (MYK-461) n=117 Participants Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.	Placebo n=122 Participants Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.
Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient.	-47 mmHg Standard Deviation 40.3	-10 mmHg Standard Deviation 29.6

SECONDARY outcome

Timeframe: 30 weeks

Cardiopulmonary exercise testing (CPET) was performed at baseline and week 30 following a study-specified protocol and peak oxygen consumption (pVO2) was determined by the Cardiovascular Metabolic Disease Research Institute (CMDRI, Palo Alto, CA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.

Outcome measures

Outcome measures
Measure	Mavacamten (MYK-461) n=120 Participants Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.	Placebo n=125 Participants Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.
Change From Baseline to Week 30 in pVO2 as Assessed by CPET	1.4 mL/kg/min Standard Deviation 3.12	-0.05 mL/kg/min Standard Deviation 3.02

SECONDARY outcome

Timeframe: 30 weeks

New York Heart Association (NYHA) functional classification was determined by the principal investigator at baseline and at specified timepoints in the study. At baseline, all subjects were NYHA Class II or III. For the secondary outcome, NYHA class at Week 30 was compared to baseline and the proportion of subjects with an improvement of at least one class was determined, and the difference between treatment groups was analyzed. The proportion was also multiplied by 100 to provide the result as a percent.

Outcome measures

Outcome measures
Measure	Mavacamten (MYK-461) n=123 Participants Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.	Placebo n=128 Participants Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.
Proportion of Participants With at Least 1 Class Improvement in NYHA Functional Class From Baseline to Week 30	80 Participants	40 Participants

SECONDARY outcome

Timeframe: 30 weeks

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a patient reported outcome instrument with minimum score = 0 and maximum score = 100 where higher score indicates better health status. There are no units to the score. The instrument utilizes a recall period of 2 weeks over which patients describe the frequency and severity of their symptoms, their physical and social limitations, and how they perceive their heart failure symptoms to affect their quality of life. The KCCQ clinical summary (KCCQ-CS) score, a prespecified secondary outcome of EXPLORER-HCM, combines the physical limitation and total symptom scores.

Outcome measures

Outcome measures
Measure	Mavacamten (MYK-461) n=92 Participants Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.	Placebo n=88 Participants Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.
Change From Baseline to Week 30 in Participant-reported Health-related Quality of Life as Assessed by the KCCQ Score	13.6 Scores on Scale Standard Deviation 14.42	4.2 Scores on Scale Standard Deviation 13.68

SECONDARY outcome

Timeframe: 30 weeks

The Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) is a patient reported outcome instrument that is a daily self-administered 11-item questionnaire. The HCMSQ assesses the core symptoms of HCM (tiredness/fatigue, heart palpitations, chest pain, dizziness, and shortness of breath). The Shortness of Breath domain score, a pre-specified secondary outcome of EXPLORER-HCM, assesses the frequency and severity of shortness of breath. The minimum score = 0 and maximum score = 18 where lower score indicates better health status. There are no units to the score.

Outcome measures

Outcome measures
Measure	Mavacamten (MYK-461) n=85 Participants Mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.	Placebo n=86 Participants Placebo: placebo capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient.
Change From Baseline to Week 30 in Participant-reported Severity of HCM Symptoms as Assessed by the HCMSQ Score	-2.8 Scores on Scale Standard Deviation 2.68	-0.9 Scores on Scale Standard Deviation 2.41

Adverse Events

Mavacamten (MYK-461)

Serious events: 14 serious events

Other events: 108 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 104 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Mavacamten (MYK-461) n=123 participants at risk mavacamten: mavacamten capsules One mavacamten 2.5, 5, 10, or 15 mg capsule once daily by mouth for 30 weeks. The starting dose of mavacamten was 5 mg once daily by mouth. At Week 6, Week 8, and Week 14, mavacamten dose may have been up-titrated or down-titrated for individual subjects based on prespecified criteria.	Placebo n=128 participants at risk Placebo: placebo oral capsule One placebo-to-match mavacamten capsule once daily by mouth for 30 weeks. A universal placebo capsule to match all strengths of mavacamten had the same appearance as mavacamten capsules but did not include the active ingredient. Placebo dose to match mavacamten capsule was administered once daily by mouth.
Cardiac disorders Atrial Fibrillation	8.1% 10/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	7.8% 10/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Cardiac disorders Palpitations	5.7% 7/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	7.8% 10/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Cardiac disorders Angina pectoris	2.4% 3/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	5.5% 7/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.6% 18/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	10.2% 13/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Respiratory, thoracic and mediastinal disorders Cough	8.1% 10/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	3.1% 4/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Nervous system disorders Dizziness	21.1% 26/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	13.3% 17/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Nervous system disorders Headache	12.2% 15/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	7.8% 10/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Nervous system disorders Syncope	5.7% 7/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	1.6% 2/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
General disorders Fatigue	5.7% 7/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	5.5% 7/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Gastrointestinal disorders Diarrhoea	4.1% 5/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	5.5% 7/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Gastrointestinal disorders Gastroesophageal reflux disease	5.7% 7/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	2.3% 3/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Musculoskeletal and connective tissue disorders Back pain	8.1% 10/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	6.2% 8/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 7/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	1.6% 2/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Infections and infestations Nasopharyngitis	12.2% 15/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	14.8% 19/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.
Infections and infestations Upper respiratory tract infection	8.1% 10/123 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.	4.7% 6/128 • Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38). Treatment with mavacamten was well tolerated with an overall completion rate \> 97%, with a balanced AE profile between treatment arms through 30 weeks of treatment. It is notable that the TEAE rate did not increase in the mavacamten group with 8 weeks of additional observation during study drug washout. Adverse event data included below is through Week 38.