Reata Pharmaceuticals Inc (NASDAQ:RETA) just announced data from an interim study of its lead blood pressure study, and they company has picked up a bit of strength on the back of the release. The trial isn’t set for primary completion before September, and end-completion is slated for December this year, but the latest release offers some level of insight into what the data might reveal come topline, so it’s more than worth taking a look at in a bit of detail. With this said, here’s our take on the drug in question and what the latest data tells us about its chances of shifting into a pivotal come the end of the year.
The drug is called bardoxolone methyl, and it’s targeting pulmonary arterial hypertension (“PAH”). In our bodies we have what’s called the lung vasculature, which comprises pulmonary arteries, veins and capillaries and it’s responsible for carrying the deoxygenated blood away from the heart towards the lungs and then bringing the oxygenated blood back to the heart after it has passed through the lungs. Certain triggers cause this system to narrow, and the narrowing causes an increase in pressure. Symptoms include tightening, aching, shortening of breath and other types of pain and swelling. Beyond that, however, and far more serious, if untreated PAH can lead to failure of the ventricles in the heart, and by proxy, death. There are a few treatment options available, and surgery is possible in some cases, but efficacy is not that great. Untreated PAH has a median survival of 2-3 years, less than some cancers. Treated PAH survival rates at 5 and 7 years are around 55% and 49% respectively. This increases slightly if the condition is familial, but not by too high a margin.
So there’s room for improvement in the treatment landscape – improvement that Reata hopes to bring to the table with its bardoxolone methyl treatment. The exact impact of this drug in PAH is unclear, as it seems to vary from patient to patient. By way of a combination of effects, however, it looks to improve PAH across the board. These effects include some anti-inflammatory impact that helps to halt fibrosis in the pathways involved in the lung vasculature, and an inhibition of what’s called NF-KB signaling, which also helps to reduce inflammation.
The trial at first glance is pretty convoluted, but when broken down it’s not too complicated. Essentially, there are 4 separate dose arms and a fifth titration arm Patients in each arm were randomized 3:1 in favor of active treatment versus placebo, and set about taking their respective doses across a 16-week period. At the end of the period, the patients who completed the study have the chance to move into an extension trial, which Reata will use to assess the long term safety of the drug.
The primary endpoint was an increase in what’s called six-minute walk distance (6MWD), which as the name makes pretty clear, is the distance a patient can walk within a six-minute period. It was measure from baseline, so the patients established a baseline at the beginning of the trial, and Reata will compare this baseline to the post dosing period 6WMD figure. We don’t have too much detail, even with the interim data announcement, but here’s what we know: that the patients in the treatment arm registered an improved 6MWD at 16 weeks, and as per the latest data, a similar increase at 32 weeks. Also tolerability was pretty good, with no real adverse events outside of what’s expected reported across the trial’s population.
The bottom line on this release is that it looks as though there is some level of efficacy, but exactly how much remains unclear. There have historically been some safety concerns with this type of treatment in other indications (a kidney disease trial discontinued in October 2012 after patients in the trial registered a higher rate of heart failure, hospitalizations, and death) but this – as yet – looks to not be too much of an issue.
The key timeframes to watch are September and December 2016. If Reata can put out data that supports its efficacy hypothesis at these dates, and there arise no significant AEs (at least, none that occur at a rate that would warrant discontinuation) then we should see some upside come completion.