Today, I talk about REGENXBIO and their in-house gene therapy candidates. Their most important asset in early clinical trials is RGX-314, indicated for wet AMD (and hopefuily Diabetic Retinopathy). This gene therapy could replace blockbuster drugs that treat millions patients, but is it a buy today?
With three times more deaths in the treatment group over placebo in their latest phase 3 trial, ESPR has taken a serious hit in value. This trial is one of many where Esperion is putting their LDL-c lowering drug, Bempedoic Acid (BA), to the test. Their data indicates that BA lowers LDL-c approximately 25% from baseline as a monotherapy or in conjunction with statins, PCSK9 inhibitors or ezetimibe. Esperion sees an opportunity in patients with atherosclerosis/hypercholesterolemia that cannot tolerate statins or cannot afford pricey PCSK9 inhibitors. According to their presentation material, 8.5-9 million patients require additional LDL-c lowering even though they are on maximally tolerated doses of statins. The CLEAR Harmony trial’s goal was to assess long-term safety and efficacy of BA in patients receiving maximally tolerated statin therapy. Patients in this trial are at high-risk for cardiovascular disease and sudden death. See the patient demographics below:
These patients are in their late 60s, overweight, and have high cholesterol. It is not surprising that a certain number of them would have expire over the course of the study. But why would the Bempedoic Acid group have more deaths than the placebo? Random chance.
Statistically speaking, there is no difference in mortality between the groups. But besides that, the cause of mortality varies tremendously between the patients. If Bempedoic Acid was the cause of death, there would be a trend that emerges from the data. Fortunately, BA is effective and doesn’t seem to cause any obvious safety issues. However, the FDA has been vague on whether or not the data accumulated to date will be sufficient to approve BA for reducing cardiovascular disease. The market is pricing this in.
Many drugs with questionable safety are required to undergo testing in a large-scale cardiovascular outcomes trial (CVOT) that is very expensive and time consuming. The ultimate goal in a CVOT is to evaluate the safety of a drug, and see whether or not it alters MACE events (major adverse cardiovascular events). This data will give the FDA confidence to provide the indication that Esperion seeks.
The next major catalyst in Esperion’s journey is top-line data from their next phase 3 clinical trials, expected in late 2018. Then, in early 2019, ESPR will file an NDA for the indication of LDL-c lowering with a plan to seek the cardiovascular risk reduction indication in 2022. I’ve taken a small position in the stock, anticipating that the positive data from the next few months will reassure stockholders of the safety of BA. I think that prescribers will see the merit of this drug and with a lower cost than PSCK9 inhibitors, will be inclined to try it with their patients.