Hi everyone.
My name is Dr. Florian Rader.
I am the co-director
of the Hypertrophic Cardiomyopathy Centre here
at Cedar-Sinai in Los Angeles, California.
And I was one of the investigators
for the MAVA-LTE trial that I'm going to present
at the ACC this year.
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Yeah, I think the backdrop of this study is
that since investigators
started to unravel the disease
of hypertrophic cardiomyopathy,
now over more than 60 years ago,
there really hasn't been
any specifically designed treatment for this disorder.
So mavacamten is probably one
of the most promising candidates for this role.
In addition, it's important to notice that many patients
with obstructive hypertrophic cardiomyopathy
have significant symptoms
and these symptoms are only partially relieved right now
with medications.
And many of those have to go
on to invasive procedures to relieve the obstruction.
So the MAVA-LTE study is a long term
open label extension
of the previous pivotal trial of mavacamten,
the EXPLORER-HCM trial for patients
with obstructive hypertrophic cardiomyopathy.
Those patients who finished the EXPLORER-HCM trial
were weaned off mavacemten,
and then re-enrolled into the long-term extension study.
This is a study we're looking at right now.
So this is an ongoing
dose-blinded but otherwise open label trial
of all patients who previously participated in EXPLORER-HCM.
So patients in the MAVA-LTE long-term extension trial
will be enrolled or followed for up to 252 weeks.
What we're looking at here
at this interim analysis is interim outcomes
of these patients at a medium follow-up duration
of 63 weeks.
Yeah, the key findings here are that very similarly
to the results in the parent study, EXPLORER-HCM,
we found significant reductions
in left ventricular outflow tract gradients.
So a relief of the obstructive portion of this disorder.
We also saw an expected decrease
in ejection fraction by about 7 to 9% during follow up.
And this is expected because the mechanism
of mavacamten does reduce the force of contraction
and that's how the obstruction is being relieved.
And importantly, I think we also saw that
along with very dramatic reductions
in NTproBNP levels,
sort of a marker of heart failure,
improvement status also improved
or a functional class, New York Heart Association
functional class improved significantly.
So specifically there were at week 48,
67.5% who improved at least one New York Heart Association
class of shortness of breath.
So based on these results.
So we already know
from the EXPLORER-HCM trial that mavacamten is effective
for relieving LVT gradients
improving functional class and symptom status
in patients with obstructive hypertrophic cardiomyopathy.
Now we sort of also have learned that longer term extension
of the use of this medication is just as effective.
And importantly, we now have more follow up data.
So we also learned more about the safety of this medication.
Overall, the safety profile
of this medication was very good.
There were of course, a large amount
of adverse events recorded during the study.
That's how we learn
about potential risks of new medications
but overall there were no new safety signals
in terms of new concerns that would make us require
more intense surveillance of echo follow up
or pharmacodynamic data
that we already knew after EXPLORER-HCM.
So I think the take-home messages are
that mavacamten continues to be the most promising contender
for a first specifically designed medication
or drug therapy for obstructive hypertrophic cardiomyopathy.
And it seems to be extremely effective
when it comes to relief of the obstructive portion
of hypertrophic cardiomyopathy.
It seems to be extremely effective
in reducing BMP levels, along with improvements
in New York Heart Association Functional class status
and another important take home message is
that the medication seems to be safe
and overall very well tolerated
and reductions in injection fraction
that only very rarely exceed the level
of 50% are in almost all instances reversible.
So this medication does seem to be very safe
and very useful for clinical practice.
I think regulators will continue to look
at the outcomes and further interim analysis
of this long term extension trial.
Like I said, this trial will go
on for a total of over 250 weeks.
So as we go along, we might learn more
about additional ways to manage these patients.
We will learn more about the durability of the medication
and we will also learn more about the long term safety
of this medication and therefore
the usefulness in clinical practice.
It also will inform, I think the question
of how frequently do we have to check echocardiograms
for example, to make sure
that ejection fraction stays in an optimal range.
So I think this will be very important
for treating physicians and practitioners
but also for regulatory bodies.
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