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This was a great day for #HCM patients. The results of EXPLORER-HCM were presented #ESC2020 and published ( https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31792-X/fulltext ). This timeline shows some of the major clinical events in #HCM
@MyoKardia
#cardiotwitter
As the figure shows, >60 years have passed since the initial clinical and pathological description of #HCM , during which tremendous advancements have been made, but mavacamten now opens a new era of therapeutics in #HCM

Excerpts from Teare's and from Morrow/Braunwald's
As the figure shows, >60 years have passed since the initial clinical and pathological description of #HCM , during which tremendous advancements have been made, but mavacamten now opens a new era of therapeutics in #HCM Excerpts from Teare's and from Morrow/Braunwald's
As the figure shows, >60 years have passed since the initial clinical and pathological description of #HCM , during which tremendous advancements have been made, but mavacamten now opens a new era of therapeutics in #HCM Excerpts from Teare's and from Morrow/Braunwald's
This can serve as a referesher for cardiac myosin inhibitors MOA -- https://twitter.com/MasriAhmadMD/status/1234630591028563968?s=20
This journey beyond phase I started with PIONEER-HCM, published in @AnnalsofIM and was led by @HeitnerStephen @DanielJacobyMD @tikuowens et al.

mavacamten decreased LVOT gradient, increased pVO2, but raised questions regarding AF at the time.

https://www.acpjournals.org/doi/10.7326/M18-3016
This journey beyond phase I started with PIONEER-HCM, published in @AnnalsofIM and was led by @HeitnerStephen @DanielJacobyMD @tikuowens et al. mavacamten decreased LVOT gradient, increased pVO2, but raised questions regarding AF at the time. https://www.acpjournals.org/doi/10.7326/M18-3016
This journey beyond phase I started with PIONEER-HCM, published in @AnnalsofIM and was led by @HeitnerStephen @DanielJacobyMD @tikuowens et al. mavacamten decreased LVOT gradient, increased pVO2, but raised questions regarding AF at the time. https://www.acpjournals.org/doi/10.7326/M18-3016
PIONEER-OLE continues to date, some insights were presented by @HeitnerStephen last year and more data have been accrued since then.

https://www.biospace.com/article/releases/myokardia-announces-48-week-data-from-pioneer-ole-study-of-mavacamten/

PIONEER-OLE continues to date, some insights were presented by @HeitnerStephen last year and more data have been accrued since then. https://www.biospace.com/article/releases/myokardia-announces-48-week-data-from-pioneer-ole-study-of-mavacamten/
PIONEER-OLE continues to date, some insights were presented by @HeitnerStephen last year and more data have been accrued since then. https://www.biospace.com/article/releases/myokardia-announces-48-week-data-from-pioneer-ole-study-of-mavacamten/
In the obstructive HCM space, EXPLORER was next, a large phase III study.

If you recall - we already found out the topline results back in May https://twitter.com/MasriAhmadMD/status/1259926841655095296?s=20
The trial was just presented at #ESC2020

If you are not registered for ESC you can still see an interview/presentation with Iacopo Olivotto here

https://www.youtube.com/embed/U_bXsa8LrAY?rel=0&autoplay=1&autoplay=1&autoplay=1
Study design -- https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.006853

Results -- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31792-X/fulltext
Study design -- https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.006853 Results -- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31792-X/fulltext
Study design -- https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.006853 Results -- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31792-X/fulltext
Study design -- https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.006853 Results -- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31792-X/fulltext
Main figures (beyond the co-primary outcome) showing improved LVOT gradients, biomarkers, NYHA class, and QoL measures. No safety concerns and most important, no difference in AF between both groups.
Main figures (beyond the co-primary outcome) showing improved LVOT gradients, biomarkers, NYHA class, and QoL measures. No safety concerns and most important, no difference in AF between both groups.
Main figures (beyond the co-primary outcome) showing improved LVOT gradients, biomarkers, NYHA class, and QoL measures. No safety concerns and most important, no difference in AF between both groups.
Main figures (beyond the co-primary outcome) showing improved LVOT gradients, biomarkers, NYHA class, and QoL measures. No safety concerns and most important, no difference in AF between both groups.
EXPLORER open label phase is ongoing, combined with the knowledge generated from PIONEER OLE.

@DesaiMilindY is leading VALOR-HCM, the next step in testing mavacamten in patients eligible for septal reduction therapies https://clinicaltrials.gov/ct2/show/NCT04349072
A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for...

A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy - Full Text View.

https://clinicaltrials.gov/ct2/show/NCT04349072
Somewhat concurrently, MAVERICK was underway - mavacamten in non-obstructive #HCM and was presented at ACC 2020 , paper is here - https://www.onlinejacc.org/content/75/21/2649

MAVERICK will inform the design of a phase III trial in non-obstructive #HCM
Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy

Background Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contra...

https://www.onlinejacc.org/content/75/21/2649
The natural next step is also testing cardiac myosin inhibitors in certain subsets of HFpEF.

And as you can imagine, on the flip side, myosin activators are being studied in HFrEF... more to come on that.
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