MyoKardia steps closer to the launch of a groundbreaking heart trial after finding its low-dose starting point

MyoKardia $MYOK is one step closer to launching a pivotal trial for its genetically targeted lead heart drug.

In the second part of their two-step Phase II trial, the South San Francisco-based biotech says it landed positive data for a slate of endpoints with their low-dose approach to obstructive hypertrophic cardiomyopathy. That’s encouraging them to drop off the top and bottom doses from the full scale up and focus on the 5 mg, 10 mg and 15 mg steps in the range.

But there’s a catch. The low-dose 2 mg-step-up-to-5 mg arm did hit goals for most endpoints, but at that level their drug mavacamten also failed to achieve a statistically significant increase in peak VO2 (exercise capacity as measured by an increase in oxygen consumption), which the company outlined earlier as the intended primary endpoint for their pivotal study, dubbed EXPLORER-HCM.

In fact, that was the only endpoint that didn’t achieve statistical significance with a p value of 0.121.

“That is the one measure that did not hit statistical significance, but that is not surprising,” MyoKardia CEO Tassos Gianakakos tells me. The researchers wanted to find the bottom of an effective range, and they have plenty of proof-of-concept data from about 20 patients in both cohorts to convince them they have good reason to believe it will work when they move to a placebo-controlled registration study with a dose that starts out at 5 mg and can rise to 15 mg. They add that you also shouldn’t just dismiss the positive trend that they saw at the low dose.

MyoKardia is breaking new ground in this study in many ways, and not just with the first new drug to be studied for this condition. It’s a small company taking on heart disease, a field dominated by giants like Novartis, which have the means to mount huge, long-running studies that cost a fortune. But the biotech isn’t taking on mass cardio conditions — it’s looking to break up its research program into tightly contained buckets of genetically defined patient groups. Its lead drug targets a mutation in heart proteins which forces the heart to squeeze more, thickening heart muscles and creating a cascade of effects and symptoms that can lead to afibrillation and death.

So they’ve been looking for the Goldilocks formulation that can achieve the right serum concentrations of the drug — permitting physicians to step up from a low dose that may well prove effective for a large chunk of patients before going on to find the right level for the rest, while not overstepping their intended impact on the heart.

MyoKardia — which has seen its hot stock more than triple in value since its first readout from their mid-stage study — had outlined a timeline for launching the registration study before the end of 2017. Now dosing is expected to get started in the second quarter.

That’s later than what they had envisioned last summer, concedes the CEO. But the executive team wants to take time for two sit-downs with the FDA, following up to make sure regulators are comfortable with the data they have, the design of the pivotal trial and the pivotal goals they’ll be using, sticking with peak VO2 for the primary.

MyoKardia is holding back from providing a timeline on the readout from the EXPLORER study. They want to get the FDA’s sign off and start dosing patients, judging how fast they can recruit the patients they need. Then they’ll tell the world what to expect.

If they’re right, MyoKardia could well be on the way to pioneering something radically new — and that’s no easy task.

Image: MyoKardia CEO Tassos Gianakakos. MYOKARDIA

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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