Mesoblast’s heart failure drug works best on very sick patients

Mesoblast [$MESO] is a company developing a handful of stem cell therapies. Right now, they have Phase 3 trials running for heart failure, low back pain, graft vs. host disease, and rheumatoid arthritis. This article will focus on MPC-150, which is the treatment MESO is testing for congestive heart failure (CHF).

MPC-150 is currently in a Phase 3 trial. The trial is testing whether injecting  150 million stem cells into the heart can improve cardiac function. Specifically, the researchers will be monitoring to see how many heart-failure related major adverse cardiac events (HF-MACE) each study group suffers.

Data from the Phase 2 studies suggests that MPC-150 will probably get a pass in Phase 3, but there are some issues with the program overall which I’ll discuss below.

Effective at Treating HF-MACE

In Phase 2 studies, researchers found that a dose of 150 million stem cells was more effective than smaller doses. On the chart below, you should be able to see that the highest dose (labeled as “150M” on the x-axis) had the greatest effect. This chart is showing the “Left ventricle end systolic volume” (LVESV) and “left ventricle end diastolic volume” (LVEDV), which are measures of how much blood is left in the heart after it pumps. Less blood remaining means that the heart is stronger and pumping more efficiently.

Smaller doses were not statistically effective.
A dose of 150 million stem cells showed the greatest improvement in cardiac function

Here you can see that the control group had an increased end volume, whereas in the 150 million stem cell dose, end volume went down. That’s good news, and in Phase 3 the researchers are testing a dose of 150 million stem cells.

However, this treatment seems to work best in patients who are very sick. This next chart shows the difference in patients who had an end volume of less than 100 milliliters (“baseline LVESV < 100 mL”) and patients who had an end volume of more than 100 milliliters (“baseline LVESV > 100 mL”). Remember, less is better.

MCP-150 works best in patients with baseline LVESV of more than 100 mL.
Sickness of patients affects how well MESO’s drug works

As you can tell, the treatment seems to be more effective in the sicker patients. This isn’t necessarily a bad thing, but it’s important to know. What I would have liked to see here are some comparisons between treatment groups, instead of just showing that the treatment was more effective against the placebo. Still, the Phase 3 trial for MPC-150 is also going to be tested on the sickest patients, so this is again good news — and about 60% of patients fall into the “sickest” group.

And finally, over a 3-year period following the same group of sickest patients, 71% of patients treated with placebo had a HF-MACE event, while none of those treated with MPC-150 did. This last piece is the strongest bit of evidence for the efficacy of MESO’s drug.

No difference in cardiac function a year after treatment, did not improve other things

However, there are a few issues. First, while the Phase 2 trial produced some improvement in cardiac function at 6 months, at the 12 month mark the MPC-150 group was no longer statistically different from the control group. This fact was ignored during $MESO’s press briefings, of course.

Second, there was no significant improvement in any of the other measures that I had expected to see improve. The biggest of these was in functional exercise capacity. The MPC-150 group was no different from the placebo group in how far they could walk during the 6-minute walk test. Given that the treatment theoretically works by improving cardiac function and helping the heart regrow a bit, I had expected to see the walk test improve. This also means that there won’t be an improvement in quality of life for the patients.


Ultimately, I can’t argue with the result that MPC-150 is keeping the sickest group of patients from having HF-MACE events. Those data were excellent and hard to refute. However, the other issues mentioned above keep me from thinking that this is a slam dunk. Given that the Phase 3 trial is testing HF-MACE on the sickest group of patients, I think that MESO will probably get a Phase 3 pass. That said, I don’t like that cardiac function declined back to the control group at 12 months, and I don’t like that no other measures of effectiveness improved.

When I invest in a biotech, I prefer it to be something like $AKAO, where there’s no doubt in my mind that the treatment works.

Prediction: Probably Phase 3 Approval

Since the Phase 3 trial is testing the most successful parts of the Phase 2 trial, MPC-150 will probably get a Phase 3 pass. Still, my lingering doubts about the ultimate effectiveness of the treatment will keep me from investing in $MESO.