PMID- 34911641
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20220531
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 44
IP  - 1
DP  - 2022 Jan
TI  - Projecting the Long-term Clinical Value of Mavacamten for the Treatment of 
      Obstructive Hypertrophic Cardiomyopathy in the United States: An Assessment of 
      Net Health Benefit.
PG  - 52-66.e2
LID - S0149-2918(21)00460-4 [pii]
LID - 10.1016/j.clinthera.2021.11.006 [doi]
AB  - PURPOSE: The aim of the study was to project the long-term net health benefits of 
      mavacamten for the treatment of symptomatic obstructive hypertrophic 
      cardiomyopathy (HCM) in the United States. METHODS: A Markov model with 4 
      mutually exclusive health states (New York Heart Association [NYHA] functional 
      classes I, II, and III/IV and death) was developed to project the life-years 
      (LYs) and quality-adjusted life-years (QALYs) over a lifetime horizon for 
      patients with symptomatic obstructive HCM receiving mavacamten with or without 
      beta-blocker (BB) or calcium channel blocker (CCB) monotherapy or placebo with or 
      without BB or CCB monotherapy. The model simulated a patient cohort with a 
      starting age of 59 years and 41% women. Transition probabilities across NYHA 
      functional classes were estimated using data from the Phase III Clinical Study to 
      Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic 
      Cardiomyopathy (EXPLORER-HCM) and the EXPLORER long-term extension (EXPLORER-LTE) 
      cohort from the Long-term Safety Extension Study of Mavacamten in Adults who Have 
      Completed MAVERICK-HCM or EXPLORER-HCM (MAVA-LTE) trial and were extrapolated 
      after week 30. The mortality risks of NYHA functional class I were assumed to be 
      the age- and sex-specific mortality risks of the US general population. The 
      mortality risks for NYHA class II and III/IV were estimated using those for class 
      I in conjunction with the relative mortality risks derived using patients with 
      obstructive HCM from a large real-world registry. Health state utilities for each 
      treatment were estimated from EXPLORER-HCM. Both LYs and QALYs were aggregated 
      over a lifetime for each treatment arm, discounted at 3% annually, and compared 
      between the 2 arms. Sensitivity analyses were conducted to evaluate the 
      robustness of the model findings. FINDINGS: Over a lifetime, treatment with 
      mavacamten with or without BB or CCB monotherapy was associated with 3.67 
      incremental LYs compared with placebo with or without BB or CCB monotherapy 
      (13.00 vs 9.33 LYs). Compared with individuals in the placebo group, patients in 
      the mavacamten group were projected to spend 6.17 additional LYs in NYHA 
      functional class I and 0.04 and 2.46 fewer LYs in NYHA functional classes II and 
      III/IV, respectively. With utilities incorporated, mavacamten with or without BB 
      or CCB monotherapy was associated with 4.17 additional QALYs compared with 
      placebo with or without BB or CCB monotherapy (11.74 vs 7.57 QALYs). In the 
      sensitivity analyses, incremental benefits ranged from 1.55 to 6.21 LYs and from 
      2.48 to 6.19 QALYs across the scenarios. IMPLICATIONS: This model projected 
      substantial net health benefits associated with mavacamten for symptomatic 
      obstructive HCM owing to improved patient survival and quality of life. The 
      projected QALY gain underscored the likely long-term clinical value of mavacamten 
      in symptomatic obstructive HCM.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Desai, Nihar
AU  - Desai N
AD  - Yale University School of Medicine, New Haven, Connecticut.
FAU - Xie, Jipan
AU  - Xie J
AD  - Analysis Group Inc, Los Angeles, California.
FAU - Wang, Yan
AU  - Wang Y
AD  - Analysis Group Inc, Los Angeles, California.
FAU - Sutton, Megan B
AU  - Sutton MB
AD  - MyoKardia Inc, a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, 
      California.
FAU - Whang, John
AU  - Whang J
AD  - Bristol Myers Squibb, Lawrence Township, New Jersey.
FAU - Fine, Jennifer T
AU  - Fine JT
AD  - MyoKardia Inc, a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, 
      California.
FAU - Garrison, Louis P Jr
AU  - Garrison LP Jr
AD  - University of Washington, Seattle, Washington. Electronic address: 
      lgarrisn@uw.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211212
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Benzylamines)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (MYK-461)
RN  - 56HH86ZVCT (Uracil)
SB  - IM
MH  - Adrenergic beta-Antagonists/therapeutic use
MH  - *Benzylamines/adverse effects
MH  - Calcium Channel Blockers/therapeutic use
MH  - *Cardiomyopathy, Hypertrophic/drug therapy/mortality
MH  - Clinical Trials, Phase III as Topic
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Quality of Life
MH  - Treatment Outcome
MH  - United States/epidemiology
MH  - *Uracil/adverse effects/analogs & derivatives
OTO - NOTNLM
OT  - Markov model
OT  - life-years
OT  - mavacamten
OT  - net health benefit
OT  - obstructive hypertrophic cardiomyopathy
OT  - quality-adjusted life-years
EDAT- 2021/12/17 06:00
MHDA- 2022/04/21 06:00
CRDT- 2021/12/16 05:38
PHST- 2021/09/21 00:00 [received]
PHST- 2021/11/05 00:00 [revised]
PHST- 2021/11/13 00:00 [accepted]
PHST- 2021/12/17 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2021/12/16 05:38 [entrez]
AID - S0149-2918(21)00460-4 [pii]
AID - 10.1016/j.clinthera.2021.11.006 [doi]
PST - ppublish
SO  - Clin Ther. 2022 Jan;44(1):52-66.e2. doi: 10.1016/j.clinthera.2021.11.006. Epub 
      2021 Dec 12.